Pathways

anabolism and catabolism

2007-12-31T23:59:00.000-05:00

Anabolism, as in ‘anabolic steroids’, refers to those metabolic processes that utilize energy to biosynthesize complex molecules and to generate growth.

The reverse process is catabolism, whereby nutrients are broken down to release energy. Catabolic processes provide intermediates for synthetic or further catabolic pathways and release energy, usually as the energy carrier molecules ATP and NADPH.

The following mnemonic may help in remembering the difference: "A B C D" : Anabolism = Biosynthesis ; Catabolism = Degradation

anabolic pathways : for a complete list see topics or sidebar • acetyl CoA pathway • Calvin cycle • C-3 • C-4 • CAM • HMG-CoA-reductase pathway • Isoprenoid biosynthesis in plants methylerythritol phosphate & HMG-CoA-reductase pathway • Light-reactions • MVA independent • Nonoxygenic photosynthesis • Oxygenic photosynthesis • Photosynthesis Overview • Photophosphorylation •

catabolic pathways: for a complete list see topics or sidebar • anaplerotic reactions • beta-oxidation • glycolysis • glyoxylate cycle • Krebs cycle • oxidative phosporylation •

catabolism

2007-12-31T23:58:00.000-05:00

(Image at left - click to enlarge) Catabolic processes provide intermediates for synthetic or further catabolic pathways and release energy, usually as the energy carrier molecules ATP and NADPH.

In the first stage of catabolism, the storage forms of proteins, triacylglycerols, and polysaccharides are broken down in the cell's cytoplasm into amino acids, fatty acids, and glucose, respectively (1).

Within the mitochondrion, the intermediates generated by catabolism of proteins, fats, and sugars (2) are delivered to the Krebs tricarboxylic (citric) acid cycle (3). The catabolism of proteins delivers pyruvate, acetyl-CoA, and oxaloacetate to the Krebs TCA cycle. Beta-oxidation of fatty acids ultimately delivers acetyl-CoA. Glycolysis generates acetyl-CoA via pyruvate.

Products of the Krebs cycle are then processed by oxidative phosporylation (4).

electron donor

2007-12-30T23:50:00.000-05:00

An electron donor passes an electron from one molecule to a second chemical compound, an electron acceptor. An electron donor is a reducing agent that is itself oxidized in the process of donating an electron

.............Donor –e^-→ Acceptor
...reducing agent –e^-→ oxidizing agent
..........oxidized –e^-→ reduced

Often the organic molecule that provides a source of electrons (donor molecule) will also serve as a source of cell carbon.

Oxidation Involves Loss of electrons, and Reduction Involves Gain of electrons (mnemonic 'oilrig').

Carbon dioxide is the most abundant form of carbon on earth and many microbes are capable, provided with enough ATP and NADH, of incorporating CO2 into cell carbon. This process is termed CO2 fixation. Organisms capable of fixing CO2 are classified as autotrophs and these include phototrophs and lithotrophs. The bacterium Pseudomonas cepacia is capable of growth on benzene (an organic molecule) alone, generating energy, via respiration and synthesizing all needed carbon molecules from it.

There are four pathways that are used for the fixation of CO2:
1. the Calvin cycle or ribulose bisphosphate pathway (RuBP),
2. the reverse tricarboxyclic acid cycle or reductive tricarboxylic acid pathway (rTCA),
3. the reductive acetyl CoA pathway (rACA),
4. the 3-Hydroxypropionate cycle.

Electron donors transfer electrons to electron acceptors during cellular respiration, resulting in the release of energy for utilization in metabolic pathways. Microorganisms, such as bacteria, obtain energy by transferring electrons from an electron donor to an electron acceptor, releasing energy for use by cellular machinery.

electron transfer chain

2007-12-30T23:40:00.000-05:00

Electron transport chains
Electron transport chains (electron transfer chains) are biochemical reaction sequences that ultimately utilize ATP synthase to produce ATP, the energy currency of life.

Only two sources of energy are available to living organisms: oxidation-reduction (redox*) reactions and photic energy (photosynthesis). Chemotrophic organisms employ redox reactions to produce ATP. Phototrophic organisms employ light as their initial energy source. Both chemotrophs and phototrophs utilize electron transport chains to convert energy into ATP.

Table Electron Transport vs Oxidative Phosphorylation :

Oxidation involves loss of electrons, and reduction involves gain of electrons (mnemonic 'oilrig').

Redox reactions
*Because electrons may not be transfered in redox reactions, oxidation is better defined as an increase in oxidation number, and reduction as a decrease in oxidation number. Oxidants are typically highly electronegative molecules. Redox reactions are chemical reactions in which electrons are transferred from a donor molecule to an acceptor molecule. The reductant (electropositive metal, hydride) transfers electrons to the electronegative oxidant. The Gibbs free energy of the reactants compared to the products provides the chemical potential energy for redox reactions.

The Gibbs free energy is the energy available (“free”) to do work. Any reaction that decreases the overall Gibbs free energy of a system (reactants → products) will proceed spontaneously with release of that energy. The transfer of electrons from a high-energy donor molecule to a lower-energy acceptor molecule can be spatially separated into a series of intermediate redox reactions within an electron transport chain. The spatial separation permits biological control of the reactions.

Many metabolic reactions involve the storage and release of biological energy by means of redox reactions. Photosynthesis involves the reduction of CO2 into sugars along with the oxidation of H2O into O2. The carbon fixing, light-independent reactions of photosynthesis employ the Calvin cycle ( C-3) in most organisms, though carbon fixation may also employ the 3-hydroxypropionate cycle, the reductive acetyl CoA pathway, or the reverse tricarboxyclic acid cycle. The reverse reaction, respiration, oxidizes sugars to produce CO2 + H2O.

In intermediate steps, reduction of oxygen accompanies the employment of reduced carbon compounds to reduce nicotinamide adenine dinucleotide (NAD+ → NADH), which then contributes to the creation of a proton gradient, which in turn drives the synthesis by ATP synthase of adenosine triphosphate (ADP + Pi → ATP).

Within animal cells, mitochondria perform similar functions to the photophosphorylation reactions within the chlorosomes of prokaryotes, the phycobilin studded thylakoid membranes of Cyanobacteria, or the chloroplasts of plant cells.

The term redox state is often used to describe the balance of NAD+/NADH and NADP+/NADPH in a biological system such as a cell or organ. The redox state is reflected in the balance of several sets of metabolites such as lactate and pyruvate, and beta-hydroxybutyrate and acetoacetate whose interconversion is dependent on these ratios. An abnormal redox state can develop in a variety of deleterious situations, such as hypoxia, shock, and sepsis.

Within mitochondria, a complex series of transmembrane proteins perform the overall reaction of oxidative phosporylation:

NADH → Complex I → Q → Complex III → cytochrome c → Complex IV → O2
.................................. ↑
...........................Complex II

Within chloroplasts, the membrane-bound pigment-protein complexes of photosystem I perform cyclic photophosphorylation, and the sequence of photosystem I & photosystem II perform noncyclic photophosphorylation (image - Z-scheme).

anaplerotic reactions

2007-12-30T10:08:00.000-05:00

Anaplerotic reactions form intermediates for the Krebs, TCA, citric acid cycle.

Two major types of anaplerotic reactions have been observed:
1. Anaplerotic carbon dioxide fixation such as the pyruvate carboxylase reaction.
2. Glyoxylate cycle used by acetogens, microorganisms that can grow on acetate as a sole carbon source in this modified TCA cycle. The enzymes isocitrate lyase and malate synthase, which convert isocitrate into succinate and malate (via glyoxylate) into the glyoxylate cycle.

Four reactions are classed as anaplerotic, although the production of oxaloacetate from pyruvate is probably the most important physiologically. The anaplerotic reactions are:

1. carboxylation of pyruvate to oxalocetate (malate can be formed similarly, though thermodynamics favour the reaction malate to pyruvate)

pyruvate + CO2 + H2O + ATP →pyruvate carboxylase→ oxaloacetate + ADP + Pi + 2H⁺

2. transamination of aspartate to oxaloacetate by aspartate aminotransferase, which allows incorporation of acetyl CoA into citrate via citrate synthase in glyoxysomes.

3. hydration of glutamate to α-ketoglutarate

glutamate + NAD⁺ + H2O →glutamate-dehydrogenase→ NH4⁺ + α-ketoglutarate + NADH + H⁺

4. β-oxidation of fatty acids to succinyl-CoA

Atheist Paths

2007-12-01T16:23:00.000-05:00

A-Deistic
Adeistic
Black Out
cosmic
Eine Kleine Nattermusing
eMusings
eVolition
Galaria
Godborygmi
Godspell Follies
Gray Matters
MetaThoughts
Mimble Wimble
Naturalism
BLogodaedaly
palimpsest
Salient
Science of Evolution
Sechuam
Sintheist
Tabula Flexuosa
The Scarlet A
Weltschauung

ambling

2007-12-01T01:00:00.000-05:00

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topics

2007-12-01T00:00:00.000-05:00

Main entry '•', some items appear more than once ':', or may be found on companion sites.
Item topics:

anabolic pathways : • anabolism and catabolism • acetyl CoA pathway • Calvin cycle • C-3 • C-4 • CAM •: Crassulacean Acid Metabolism : eicosanoid biosynthesis : Hatch-Slack pathway • electron transfer chain : redox reactions • HMG-CoA-reductase pathway : Isoprenoid biosynthesis in plants methylerythritol phosphate & HMG-CoA-reductase pathway • Light-reactions •: MEP pathway : mevalonate pathway : mevalonate-dependent (MAD) route : MVA independent • Photosynthesis Overview •: cyclic photophosphorylation :• Light-reactions •: noncyclic photophosphorylation :• Nonoxygenic photosynthesis • Oxygenic photosynthesis • Photophosphorylation •: cyclic photophosphorylation : noncyclic photophosphorylation :• Nonoxygenic photosynthesis • Oxygenic photosynthesis : redox reactions : electron transfer chain :

Carbon fixation in prokaryotes: • Calvin cycle = C-3 • 3-hydroxypropionate cycle • reductive acetyl CoA pathway • reverse tricarboxyclic acid cycle • Carbon fixation in Cyanobacteria, prochlorophytes, algae: • Calvin cycle = C-3 = RuBP • Carbon fixation in Plants : • C-3 • C-4 • CAM •: Crassulacean Acid Metabolism ••

catabolic pathways: acetyl-CoA : aerobic respiration • anabolism and catabolism • anaplerotic reactions • beta-oxidation • glycolysis • glyoxylate cycle : catabolism and anabolism • catabolism : citric acid cycle • Krebs cycle • oxidative phosporylation : respiration - aerobic ››› respiratory burst • : TCA cycle : tricarboxylic acid cycle • : image catabolism vs anabolism :

Prokaryote metabolism: Carbon fixation in Cyanobacteria, prochlorophytes: • Calvin cycle = C-3 = RuBP • Metabolism • glyoxylate cycle • 3-hydroxypropionate cycle • rACA • reductive acetyl CoA pathway • reverse tricarboxyclic acid cycle • rTCA • RuBP
• Prokaryote Physiology & Communication• Interactions in Bacteria • Bacterial motility • Phosphorylation switches • Photosynthetic bacteria • Prokaryote Genetics & Biochemistry• Control of gene expression • Recombinant DNA Restriction Enzmes Restriction Endonucleases • Horizontal Gene Transfer • Conjugation • Transduction • Transformation • Symbiosis •

reactions : • anaplerotic reactions • Light-reactions • phosphorylation • pyruvate dehydrogenase reaction •: redox reactions •

redox reactions : • electron donor • electron transfer chain : redox reactions •

Diagrams Section · Photosynthesis : ·· Z-scheme of noncyclic photophosphorylation Section · Metabolism : ·· autotroph ·· Denitrification ·· chemoautotroph chemoheterotroph chemolithotroph ·· heterotroph ·· lithotroph ·· Nitrification ·· Nitrogen cycle ·· noncyclic photophosphorylation ·· photoautotroph photoheterotroph phototroph ·· Trophism ·· Z-scheme of noncyclic photophosphorylation ··

Tables: main table, ·· alternate alphabetic description. Section · Lipids lipoproteins
saturation of triacylglygerols : Section · Prokaryotes : ·· electron acceptors Electron acceptors for respiration and methanogenesis in prokaryotes ·· Embden-Meyerhof ·· Entner-Doudoroff ·· glycolysis Glycolysis in bacteria ·· lithotrophs ·· Lithotrophic prokaryotes ·· methanogenesis ·· phosphoketolase ·· respiration ·· bacterial photosynthesis ·· Section · Metabolism Electron Transport vs Oxidative Phosphorylation Enzymes Cofactors of Krebs Cycle ·· Section · Molecular Genetics gene regulation in E.coli ·· ·· ·· Section· Photosynthesis : Comparison of Photosynthesis and Respiration Comparison of plant and bacterial photosynthesis Comparison of C-3, C-4, CAM plants Overview of Photosynthesis Structure of bacteriochlorophylls ··

images: image ATP structure : image NAD structure : image CoA : image substrate level phosphorylation : image plasma membrane E.coli : image model fermentation :

Alphabetic : A • acetyl CoA pathway : aerobic respiration :• anabolism and catabolism •: aspartate to oxaloacetate : B • beta-oxidation : C • Calvin cycle • C-3 • C-4 • CAM • : carboxylation of pyruvate to oxalocetate : • catabolism : catabolism and anabolism :choline-folate-methionine : citric acid cycle : G • glycolysis : glutamate to α-ketoglutarate • glyoxylate cycle : H : Hatch-Slack pathway • 3-hydroxypropionate cycle • HMG-CoA-reductase pathway : I : Isoprenoid biosynthesis by MEP & Isoprenoid biosynthesis by HMG Co A : K • Krebs cycle : M : methylerythritol phosphate (MEP) pathway : mevalonate pathway : mevalonate-dependent (MAD) route • : N: nitrogen assimilation : P: • pentose-phosphate pathway • photorespiration : pyruvate to oxalocetate : photosynthesis : • C-3 • C-4 • CAM • Calvin cycle : Photosynthesis Overview • Photophosphorylation •: cyclic photophosphorylation : noncyclic photophosphorylation :Nonoxygenic photosynthesis • Oxygenic photosynthesis • Light-reactions : R • redox reactions • rACA • reductive acetyl CoA pathway : respiration - aerobic ››› respiratory burst • reverse tricarboxyclic acid cycle • rTCA • RuBP : S • sulfur metabolism : T : TCA cycle : transamination of aspartate to oxaloacetate : tricarboxylic acid cycle : U • urea cycle : W : Wood Ljungdahl Pathway :
organelles : • chloroplast :

• ghrelin, leptin, melanocortin, obestatin : internal :

acetyl CoA pathway

2006-12-30T21:36:00.000-05:00

The acetyl CoA pathway is also called the Wood Ljungdahl Pathway. The acetyl-CoA pathway comprises two reductive branches, the methyl branch and the carbonyl branch, both of which reduce CO2 and fix CO2-derived carbon into covalently bonded forms.

The pathway allows bacteria to grow on sugars or on H2/CO2 :
4H2 + 2 CO2 = CH3COOH + 2 H2O
4H2 + 2 CO2 = CH3COOH + 2CO.

Althought the acetyl-CoA pathway can be presented in a cyclic form (Wood and Ljungdahl), it is a linear process that does not depend on multi-carbon intermediates to which CO2 is fixed in a cyclic fashion. For example, the Calvin (C-3) cycle is a CO2-fixing processes that depends upon ribulose biphosphate for the initial fixation of CO2, and the reductive (reverse) tricarboxylic acid cycle depends upon oxalacetate for the initial fixation of CO2. Although the cofactors and electron carriers of the acetyl-CoA pathway pathway cycle between different states, the pathway itself is linear relative to carbon flow.

AcetylCoA and acetacetylCoA: amino acids : mnemonic:"A Lighter Lease" (A LyTr LeIs): A=AcetylCoA or Acetoacetyl CoA Ly=Lysine Tr=Tryptophan Le=Leucine Is=Isoleucine

external table - enzymes of Acetyl CoA pathways : Saccharomyces cerevisiae carbon monoxide dehydrogenase pathway : Arabidopsis thaliana carbon monoxide dehydrogenase pathway : MetaCyc reductive acetyl coenzyme A pathway :

beta-oxidation

2006-12-29T23:46:00.000-05:00

Most tissues utilize fatty acids as a major source of energy. Fatty acids are more highly reduced than carbohydrates, providing more energy during oxidation. Mitochondrial beta-oxidation of fatty acyl-CoAs is the first stage of utilization – the fatty acylCoA is reduced in a sequence of steps with released energy captured by the reduced energy carriers NADH and FADH₂. Four enzymatic reactions split the molecule at the single CC bond between the (alpha) and (beta) carbons: dehydrogenation by long chain acyl-CoA dehydrogenase (FAD⁺), hydration, dehydrogenation (NAD⁺), and thiolysis. The cycle is repeated, shortening the fatty acyl-CoA by two Cs, in the "beta oxidation spiral".

Ultimately, even-chained fatty acids yield 2-C acetyl-CoA while odd-chained fatty acids yield 3-C propionyl-CoA. The 2-C acetyl-CoA generated in beta-oxidation enters the Krebs cycle, where it is further oxidized to CO₂, producing more reduced energy carriers (NADH & FADH₂). The 3-C propionyl-CoA is converted to succinyl-CoA, which then enters the Krebs cycle. The reduced energy carriers transfer their energy to the electron transport chain where they drive the proton gradient that supports mitochondrial ATP production.

Beta-oxidation Pathway : Beta-Oxidation of Fatty Acids (even chain) : Beta-oxidation of Fatty Acids (odd chain)

Calvin cycle

2006-12-28T23:57:00.000-05:00

The Calvin cycle is a light independent ("dark-reaction") process of carbon fixation that takes place in the chloroplast. The Calvin cycle is also called the ribulose bisphosphate pathway (RuBP) for the initial enzyme in CO2 fixation, ribulose bisphosphate carboxylase/oxygenase, which is the most abundant and arguable the most important enzyme on earth. The near ubiquity of the RuBP makes it one of the most important biosynthetic cycles on earth because it is used by most photosynthetic organisms (plants, cyanobacteria, purple and green bacteria) to incorporate CO2 into cell carbon. Although all higher organisms eventually obtain their carbon from the products of this cycle, RuBP is not solely the providence of photosynthetic organisms since many other autotrophs use RuBP, making it by far the most commonly found method for CO2 fixation in nature. In eukaryotes, the TCA cycle links the oxidative breakdown of carbon compounds with biosynthesis and energy metabolism. In prokaryotes, the process is reversed, with the oxidation of inorganic compounds (such as CO2) providing the means for carbon assimilation.

The Calvin cycle utilizes light energy stored as ATP and NADPH to convert CO ₂ and H₂O to organic compounds. (C-3) Intermediates generated within the Calvin cycle enter central metabolic pathways as substrates in the synthesis of carbohydrates including glucose. The Calvin cycle occurs in all photosynthetic eukaryotes and most photosynthetic prokaryotes. The mechanism is most likely more than 2 billion years old and it pre-dates the appearance of oxygenic photosynthesis in the first Cyanobacteria.

6 CO₂ + 12 NADPH + 12 H⁺ + 18 ATP → C₆H₁₂O₆ + 6 H₂O + 12 NADP⁺ + 18 ADP + 18 Pi

image of pathway MetaCyc Calvin cycle :

Enzymes of the Calvin cycle are functionally equivalent to many enzymes involved in other metabolic pathways such as glycolysis and gluconeogenesis, but they are located in the chloroplast stroma rather than in the cytoplasm, thus functionally separating the reactions.

The enzymes are activated by light (hence light independent rather than "dark reaction") and by products of the light-dependent photosynthetic reactions. These regulatory mechanisms prevent the Calvin cycle from operating in reverse to respiration, thus preventing a continuous cycle of CO₂ reduction to carbohydrates occurring simultaneously with carbohydrate oxidation to CO₂ (respiration). This regulation prevents the waste of energy (as ATP) in simultaneous reverse reactions that would have no net productivity.

Table ~ Comparison Photosynthesis Respiration : Table ~ Comparison Plant Bacterial Photosynthesis : Table ~ comparison of C-3, C-4, CAM plants : Table ~ Photosynthesis Overview : Microtextbook Carbon Assimilation :: image_Calvin cycle : image_reductive tricarboxylic acid cycle : image_reductive CoEnzymeA cycle : image_3-hydroxypropionate cycle :: Saccharomyces cerevisiae carbon monoxide dehydrogenase pathway : Arabidopsis thaliana carbon monoxide dehydrogenase pathway : MetaCyc reductive acetyl coenzyme A pathway :

C-3

2006-12-28T23:56:00.000-05:00

Left (click to enlarge) : The C-3 or reductive pentose phosphate cycle (RPP).

This reaction, in which carbon is fixed, reduced, and utilized, involves the formation of intermediate sugar phosphates in a cyclic sequence. One complete RPP cycle incorporates three molecules of carbon dioxide and produces one molecule of the three-carbon compound glyceraldehyde 3-phosphate.

The C-3 pathway proceeds in three stages:
1. CO2 fixation (carboxylation) by Rubisco,
2. Carbon reduction to (CH2O)
12 PGA + 12 ATP -> 12 bisPGA + 12 NADPH + 12 H+ -> 12 GAP + 12 NADP+ + 12 Pi, and
3. Regeneration of the CO2 acceptor moleucle (ribulose 1,5-bisphosphate).

Some of the glyceraldehyde 3-phosphate generated in the reductive stage undergoes gluconeogenesis to form glucose. In plants, glucose is converted to sucrose or starch for later use.The C-3 reactions are sometimes called the "dark reactions" of photosynthesis because photon energy is not used directly – the reactions are light-independent. However, ATP and NADPH generated by light-dependent photophosphorylation reactions are required.

Table ~ comparison of C-3, C-4, CAM plants :

The reaction cycle employs combinations of different length sugar-phosphates and eventually regenerate RuBP in addition to sugar-phosphate for sucrose/starch synthesis:
3-GAP (3 C) → DHAP (3 C)
DHAP (3C) + GAP (3 C) → fructose-1,6-bisphosphate (6C)
fructose-1,6-bisP (6C) + H2O → fructose-6-P (6C) + Pi
fructose-6-P (6 C) + GAP (3 C) → Xylulose-5-phosphate (5 C) + erythrose-4-phosphate (4 C)erythrose 4-P (4 C) + DHAP (3 C) → sedoheptulose 1,7-bisphosphate (7 C)
sedoheptulose 1,7-bisP + H2O → sedoheptulose 7-P + Pi
sedoheptulose 7-P (7 C) + GAP (3 C) → xylulose 5-phosphate (5 C) + ribose 5-phosphate (5 C)
xylulose 5-P or ribose 5-P → ribulose 5-Pribulose 5-P + ATP → RuBP (more)

: animation :Table ~ Comparison Photosynthesis Respiration : Table ~ Comparison Plant Bacterial Photosynthesis : Table ~ comparison of C-3, C-4, CAM plants : Table ~ Photosynthesis Overview : Microtextbook Carbon Assimilation :: image_Calvin cycle : image_reductive tricarboxylic acid cycle : image_reductive CoEnzymeA cycle : image_3-hydroxypropionate cycle :: Saccharomyces cerevisiae carbon monoxide dehydrogenase pathway : Arabidopsis thaliana carbon monoxide dehydrogenase pathway : MetaCyc reductive acetyl coenzyme A pathway :

C-4

2006-12-28T23:55:00.000-05:00

The initial CO2 fixing enzyme in the C-4 pathway is phosphoenolpyruvate carboxylase, or PEPcase, which has a higher affinity for CO2 than Rubisco. Fixation of carbon in the mesophyll of C-4 plants prevents wasteful photorespiration by Rubisco.

In the mesophyll, PEPcase fixes CO2 as 4-carbon compounds:
PEP carboxylase + PEP + CO2 → oxaloacetate (C4)
oxaloacetate → malate (C4)

CO2 is taken up by cells of the mesophyll, where PEPcase fixes CO2 as 4-carbon oxaloacetate and malate before transport to the bundle sheath, a specialized tissue in which photosynthetic carbon reduction (C-3) takes place in bundle sheath cell chloroplasts.

Conversion of 4-carbon malate to 3-carbon pyruvate releases CO2 to the bundle cell's Calvin cycle, where 3-phosphoglycerate is furmed under the action of Rubisco. Pyruvate is phosphorylated in the mesophyll into PEP by the phosphorus group donated by a single molecule of ATP. PEP is again utilized to fix CO2 and form PEP carboxylase under the enzymatic action of PEPcase (phosphoenolpyruvate carboxylase)

The C-4 pathway consumes 30 ATP for the synthesis of one molecule of glucose, while the C-3 pathway consumes 18 ATP for the synthesis of one molecule of glucose. However, the reduction of wasteful photorespiration by Rubisco, in which tropical plants lose more than half photosynthecized carbon, more than compensates for the extra cost of ATP.

Table ~ comparison of C-3, C-4, CAM plants :

The C-4 pathway is also called the Hatch-Slack pathway for its Australian co-discoverers. The pathway is a more recent evolutionary development than the C-3 cycle.

Table ~ Comparison Photosynthesis Respiration : Table ~ Comparison Plant Bacterial Photosynthesis : Table ~ comparison of C-3, C-4, CAM plants : Table ~ Photosynthesis Overview : Microtextbook Carbon Assimilation :: image_Calvin cycle : image_reductive tricarboxylic acid cycle : image_reductive CoEnzymeA cycle : image_3-hydroxypropionate cycle :: Saccharomyces cerevisiae carbon monoxide dehydrogenase pathway : Arabidopsis thaliana carbon monoxide dehydrogenase pathway : MetaCyc reductive acetyl coenzyme A pathway :

CAM

2006-12-28T23:54:00.000-05:00

CAM is the acronym for Crassulacean Acid Metabolism, named for the Crassulaceae plant family in which it was discovered.

The chemical reaction of CO2 accumulation is similar to that of C4 plants, but in CAM plants CO2 fixation and its assimilation are separated temporally rather than spatially. CAM plants occur mainly in arid regions. The opening of the stomata to take up CO2 is always connected with large losses of water. To reduce this trans-stomatal loss during intense sun (transpiration via the cuticle continues) CAM plants utilize a mechanism that permits the uptake of carbon dioxide during the night. Prefixed CO2 is stored in the vacuoles as malate (and isocitrate) and is subsequently utilized during the daytime in the C-3 cycle.

Table ~ comparison of C-3, C-4, CAM plants : Table ~ Comparison Photosynthesis Respiration : Table ~ Comparison Plant Bacterial Photosynthesis : Table ~ Photosynthesis Overview : Microtextbook Carbon Assimilation :: image_Calvin cycle : image_reductive tricarboxylic acid cycle : image_reductive CoEnzymeA cycle : image_3-hydroxypropionate cycle :: Saccharomyces cerevisiae carbon monoxide dehydrogenase pathway : Arabidopsis thaliana carbon monoxide dehydrogenase pathway : MetaCyc reductive acetyl coenzyme A pathway :

choline-folate-methionine

2006-12-28T23:39:00.000-05:00

eicosanoid biosynthesis

2006-12-26T15:47:00.000-05:00

Eicosanoids, or icosanoids function as autocrine and paracrine mediators, and are oxygenated hydrophobic derivatives of 20-carbon polyunsaturated essential fatty acids, predominantly arachidonic acid (AA) in humans. Dihomo-gamma-linolenic acid (DGLA) and eicosapentaenoic acid (EPA, icosapentaenoic acid, timnodonic acid) also serve as eicosanoid precursors. Eicosanoids include leukotrienes with four double bonds and prostanoids with two double bonds (prostaglandins and prostacyclins with five-membered rings, and thromboxanes with heterocyclic oxane structures).

Eicosanoids are not stored within cells, rather they are synthesized as required in response to hormonal signals. Eicosanoids function close to the site of synthesis (autocrine, paracrine), where they are rapidly deactivated before they enter circulation as inactive metabolites.
Table Eicosanoid Actions

The first step in eicosanoid biosynthesis is phospholipase-catalyzed release from phospholipids (A2) or diacylglycerol (C) of a 20-carbon essential fatty acid (EFA) containing three, four, or five double bonds (ω-6 DGLA, ω-6 AA or ω-3 EPA, respectively).

------------------free free fatty acid released from membrane phospholipid
--------------------------↓------------------------↓------------ - ---↓
------------------cyclooxygenase------------epoxidase-------lipoxygenease
------------------- ------↓------------------------↓------------------↓
-------------------- prostanoids----------------EETs-------5-HPETE, HPETEs
----------------.---------↓-------------------------------------------↓
-----------prostaglandins, thromboxanes---------leukotrienes, 5-HETE, HETEs

Cyclooxygenase pathways:
En route to the prostanoids, membrane-released fatty acids are acted upon by one of two related enzymes, cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2). Prostanoids include prostaglandins, prostacyclins, and thromboxanes. The cyclooxygenases are alternatively termed prostaglandin endoperoxide H synthases-1 and -2 (PGHS-1, PGHS-2). The COX enzymes are targetted by NSAIDs (non-steroidal anti-inflammatory drugs). ASA and early NSAIDs inhibit both COX-1 and COX-2, and are associated with gastric irritation. The COX-2 inhibitors are more selective and gastro-protective, but inhibition of cardio-protective, anti-coagulative PGF2 is associated with increased risk of cardiovascular thrombotic events.

Both COX-1 and COX-2 catalyze equivalent reactions at different sites. Prostaglandin PGH2 synthase contains two catalytic centers, a cyclooxygenase and a peroxidase. In the enzymatic reactions, two molecules of oxygen are added to arachidonic acid to form a bicyclic endoperoxide then a further hydroperoxy group is added to position 15 to form prostaglandin PGG2. The hydroperoxide is next reduced by a functionally coupled peroxidase reaction to generate the unstable intermediate prostaglandin PGH2. All other prostanoids are derived from the unstable PGH2 intermediate by a variety of different enzymic reactions. Cell type determines the nature and proportions of the various enzymes, which differ in amino acid sequence, structure and cofactor requirements, and so of the prostanoids generated. (more detail, diagram)

For example:
prostaglandin A synthase : PGH2 → PGA2
prostaglandin D synthase : PGH2 → PGD2
prostaglandin E synthase : PGH2 → PGE2
prostacyclin synthase : PGH2 → PGI2 (prostacyclin)
thromboxane A synthase : PGH2 → TXA2 (thromboxane A)

One prostaglandin can be converted to another by spontaneous rearrangement, dehydration, or isomerization. Thromboxane A is deactivated by non-enzymatic hydrolysis to TXB

Lipoxygenases are a family non-heme iron enzymes that catalyze the substitution of oxygen for hydrogen in the bis-allylic position of fatty acids to generate hydroperoxide products, which are further metabolized to leukotrienes and lipoxins. (left -click to enlarge - 5-HPETE is 5S-hydroperoxy-6t,8c,11c,14c-eicosatetraenoic acid, and is generated in the reaction catalyzed by 5-LOX).

5-LOX employs nuclear-membrane protein cofactor 5-lipoxygenase-activating protein (FLAP). 5-LOX produces the primary precursor 5-HPETE then leukotriene A4 (LTA4), which may be converted into LTB4 (image at left) by the enzyme leukotriene A4 epoxide hydrolase. In animal tissues, lipoxygenase catalyzed reactions with free arachidonic acid produce specific eicosanoid hydroperoxides for 5-LOX, 8-LOX, 12-LOX, and 15-LOX. Lipoxygenases can also generate hydroperoxides from phospholipids within membranes, disturbing the membrane structure.

In eosinophils, mast cells, and alveolar macrophages, the enzyme leukotriene C4 synthase is employed to conjugate LTA4 plus glutathione to generate leukotriene C4 (LTC4). Glutathione contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side chain. Once LTC4 has been secreted, a glutamic acid moiety is removed from it to produce leukotriene D4 (LTD4), which is cleaved by dipeptidases to generate leukotriene E4 (LTE4). LTC4, LTD4 and LTE4 are termed cysteinyl leukotrienes because all contain cysteine.

Epoxytrienoic acids (EETs) are generated from arachidonic acid through the epoxidase (epoxygenase) pathway. (right) This mechanism yields four cis-epoxyeicosatrienoic acids (14,15-, 11,12-, 8,9-, and 5,6-EETs). There are several isozymes of the cytochrome P450 epoxygenase that act upon un-esterified substrates, producing all four EET regioisomers, which may be subsequently esterified. Epoxyeicosatrienoic acids (EETs) are considered antihypertensive because they elicit vasodilation and oppose the K(+)-channel stimulatory actions of 20-HETE, in addition to modulation of the activity of angiotensin II. It has also been proposed that EETs are endothelium-derived hyperpolarizing factors (EDHFs) that mediate the nitric oxide (NO)- and prostaglandin-independent vascular effects of acetylcholine (Ach) and bradykinin.

Epoxide hydrolases metabolize EETs to the corresponding dihydroxyeicosatrienoic acids (DHET). Isozymes of the epoxide hydrolases are found in different cellular locations – cytosolic or membrane-bound.

Eicosanoid Actions

tags [Biochemistry] [Molecular Biology] [eicosanoid] [phospholipid][NSAID]

glycogenolysis

2006-12-24T12:02:00.000-05:00

Glycogenolysis generates glucose from glycogen (glycogen-lysis) in response to adrenalin.

glycolysis

2006-12-24T12:01:00.000-05:00

In glycolysis, a molecule of glucose is oxidized to two molecules of pyruvic acid. Glycolysis generates the energy carrier molecules ATP and NADH in addition to intermediates (3-C or 6-C) for biosynthetic pathways.

Glycolysis sequence: Glucose → Glucose-6-P Fructose-6-P → Fructose-1,6-diP Dihydroxyacetone-P → Glyceraldehyde-P 1,3-Biphosphoglycerate → 3-Phosphoglycerate 2-Phosphoglycerate (to) Phosphoenolpyruvate [PEP] Pyruvate • mnemonic:"Goodness Gracious, Father Franklin Did Go By Picking Pumpkins (to) Prepare Pies"

Glycolysis Enzymes : Hexokinase, Phosphohexo isomerase, Phosphofructokinase-1 (6-phosphofructo-1 kinase), Aldolase, Triose phosphate isomerase, Glyceraldehyde 3-phosphate dehydrogenase, Phosphoglycerate kinase, Phosphoglycerate mutase, Enolase, Pyruvate kinase • mnemonic: “Hungry Peter Pan And The Growling Pink Panther Eat Pies.”

glyoxylate cycle

2006-12-24T12:00:00.000-05:00

Bacteria and some species of higher plants are able to obtain a net increase in malate or oxaloacetate through expression of enzymes of the glyoxylate cycle or glyoxylate shunt. The enzymes of the TCA cycle and the glyoxylate cycle are physically segragated, with the glyoxylate cycle enzymes of some plants localized in a specialized organelle called the glyoxysome. The two additional enzymes that permit the glyoxylate shunt are isocitrate lyase and malate synthase, which convert isocitrate to succinate or to malate via glyoxylate (reaction).

Glyoxysomes import fatty acids and aspartate, which provide acetyl-CoA to the shunt. The glyoxysome lacks means for reoxidizing NADH, so has none of the dehydrogenases of the TCA cycle. Aspartate transaminase (aspartate aminotransferase) converts aspartate into oxaloacetate, permitting incorporation of acetyl CoA into citrate via citrate synthase. Glyoxysomal aconitase is present, but isocitrate lyase is found in the glyoxysome instead of isocitrate dehydrogenase. The succinate generated by the lyase is then exported back to the mitochondria since there is no glyoxysomal succinate dehydrogenase. (diagram) Mitochondria oxidize succinate to oxaloacetate, and aspartate transminase converts it back to aspartate, maintaining the cycle. Meanwhile, the glyoxysomes incorporate a second acetyl CoA to produce malate, which is exported to the cytoplasm for gluconeogenesis.

Two acetyl CoA are input per glyoxylate cycle with no loss of CO2, making possible net synthesis of a 4-carbon product. (diagram) The glyoxylate cycle bypasses reactions of TCA cycle in which CO2 is released, conserving 4 carbon compounds for biosynthesis. The glyoxylate cycle is also called the glyoxylate bypass or glyoxylate shunt. The anaplerotic glyoxylate pathway is active when growth on 2 carbon compounds requires conservation of 4 carbon TCA intermediates. Two molecules of acetylCoA are taken up per turn of the glyoxylate cycle, and acetylCoA is generated by acetate thiokinase in the reaction:

acetate + CoA + ATP = acetyl-CoA + AMP + Pi

Alternatively, acetylCoA is generated by β oxidation of fatty acids. The glyoxylate cycle is repressed during growth on glucose, and induced by growth on acetate.

The the net reaction is
2 acetyl-CoA + NAD⁺ → succinate + 2 CoA + NADH + H⁺

Superpathways: superpathway of glyoxylate bypass and TCA , superpathway of glycolysis, pyruvate dehydrogenase, TCA, and glyoxylate bypass : Variants: TCA cycle , pyruvate oxidation pathway , pyruvate dehydrogenase complex :

HMG-CoA-reductase pathway

2006-12-23T23:27:00.000-05:00

The HMG-CoA reductase pathway is also called the mevalonate pathway or the mevalonate-dependent (MAD) route. The HMG-CoA reductase pathway is an important cellular metabolic pathway present in almost all organisms. The pathway generates hydrophobic molecules for diverse tasks such as maintenance of cell membranes, production of hormones, anchoring of proteins, and for N-glycosylation.

Plants can generate isoprenoids by way of the HMG-CoA reductase pathway and the methylerythritol phosphate or MEP pathway, which is also called the MVA independent pathway, in plastids. Isoprenoid biosynthesis pathways in the plant cell. HMG-CoA, Hydroxymethylglutaryl CoA - small image + legend, 242 k image.

Several key enzymes of the pathway can be activated through DNA transcriptional regulation on the activation of SREBP (Sterol Regulatory Element-Binding Protein-1 and -2). This intracellular sensor detects low levels of cholesterol and stimulates endogenous production by the HMG-CoA reductase pathway, in addition to increasing lipoprotein uptake by up-regulating the LDL receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation. Because cholesterol is a product of the HMG-CoA reductase pathway, several drugs target the pathway. These include Statins, which are used to treat elevated cholesterol levels, and Bisphosphonates, which are used to treat osteoporosis.

3-hydroxypropionate cycle

2006-12-23T01:40:00.000-05:00

In addition to RuBP, rTCA, and rACA, a fourth pathway has been discovered for CO2 assimilation in bacteria, the 3-hydroxypropionate cycle. In this cycle, CO2 is fixed by acetyl-CoA and propionyl-CoA carboxylases ultimately forming malyl-CoA, which is then split into acetyl-CoA (to replenish the cycle) and into glyoxylate, for use in cell carbon. Past research had demonstrated this pathway only in Chloroflexus, a nonsulfur photosynthetic bacterium, but recent work has detected the pathway in several autotrophic archaea, so it seems the pathway is more widespread than previously thought.

Table ~ comparison of C-3, C-4, CAM plants : Microtextbook Carbon Assimilation : Table ~ Comparison Photosynthesis Respiration : Table ~ Comparison Plant Bacterial Photosynthesis : Table ~ Photosynthesis Overview :: image_Calvin cycle : image_reductive tricarboxylic acid cycle : image_reductive CoEnzymeA cycle : image_3-hydroxypropionate cycle :: Saccharomyces cerevisiae carbon monoxide dehydrogenase pathway : Arabidopsis thaliana carbon monoxide dehydrogenase pathway : MetaCyc reductive acetyl coenzyme A pathway :

Genomics Sheds Light on Metabolism of Cryptic Marine Microbes
To search for genetic clues to carbon and energy metabolism in Crenarchaeota, the researchers extracted C. symbiosum DNA from its host sponge and constructed a DNA library for sequencing the symbiont’s genome. Hallam et al. then searched for representative genes linked to pathways associated with autotrophic carbon assimilation. They found many components of two pathways: the 3-hydroxypropionate cycle and the reductive tricarboxylic acid (citric acid) pathway (TCA). Both cycles involve a multistep series of chemical reactions that convert inorganic compounds—in this case, carbon dioxide—into organic carbon molecules. Though some components of the 3-hydroxypropionate cycle were missing in C. symbiosum, enough elements (including core proteins) were found to support a modified version of this pathway for carbon assimilation, using carbon dioxide.
Liza Gross, Genomics Sheds Light on Metabolism of Cryptic Marine Microbes, PLoS Biology Volume 4 Issue 4 APRIL 2006

G Strauss and G Fuch, Enzymes of a novel autotrophic CO2 fixation pathway in the phototrophic bacterium Chloroflexus aurantiacus, the 3-hydroxypropionate cycle. European Journal of Biochemistry, Vol 215, 633-643

Presence of Acetyl Coenzyme A (CoA) Carboxylase and Propionyl-CoA Carboxylase in Autotrophic Crenarchaeota and Indication for Operation of a 3-Hydroxypropionate Cycle in Autotrophic Carbon Fixation.
The pathway of autotrophic CO2 fixation was studied in the phototrophic bacterium Chloroflexus aurantiacus and in the aerobic thermoacidophilic archaeon Metallosphaera sedula. In both organisms, none of the key enzymes of the reductive pentose phosphate cycle, the reductive citric acid cycle, and the reductive acetyl coenzyme A (acetyl-CoA) pathway were detectable. However, cells contained the biotin-dependent acetyl-CoA carboxylase and propionyl-CoA carboxylase as well as phosphoenolpyruvate carboxylase. The specific enzyme activities of the carboxylases were high enough to explain the autotrophic growth rate via the 3-hydroxypropionate cycle. Extracts catalyzed the CO2-, MgATP-, and NADPH-dependent conversion of acetyl-CoA to 3-hydroxypropionate via malonyl-CoA and the conversion of this intermediate to succinate via propionyl-CoA. The labelled intermediates were detected in vitro with either 14CO2 or [14C]acetyl-CoA as precursor. These reactions are part of the 3-hydroxypropionate cycle, the autotrophic pathway proposed for C. aurantiacus. The investigation was extended to the autotrophic archaea Sulfolobus metallicus and Acidianus infernus, which showed acetyl-CoA and propionyl-CoA carboxylase activities in extracts of autotrophically grown cells. Acetyl-CoA carboxylase activity is unexpected in archaea since they do not contain fatty acids in their membranes. These aerobic archaea, as well as C. aurantiacus, were screened for biotin-containing proteins by the avidin-peroxidase test. They contained large amounts of a small biotin-carrying protein, which is most likely part of the acetyl-CoA and propionyl-CoA carboxylases. Other archaea reported to use one of the other known autotrophic pathways lacked such small biotin-containing proteins. These findings suggest that the aerobic autotrophic archaea M. sedula, S. metallicus, and A. infernus use a yet-to-be-defined 3-hydroxypropionate cycle for their autotrophic growth. Acetyl-CoA carboxylase and propionyl-CoA carboxylase are proposed to be the main CO2 fixation enzymes, and phosphoenolpyruvate carboxylase may have an anaplerotic function. The results also provide further support for the occurrence of the 3-hydroxypropionate cycle in C. aurantiacus.
Castor Menendez, Zsuzsa Bauer, Harald Huber, Nasser Gad'on, Karl-Otto Stetter, and Georg Fuchs, Presence of Acetyl Coenzyme A (CoA) Carboxylase and Propionyl-CoA Carboxylase in Autotrophic Crenarchaeota and Indication for Operation of a 3-Hydroxypropionate Cycle in Autotrophic Carbon Fixation. Journal of Bacteriology, February 1999, p. 1088-1098, Vol. 181, No. 4

Occurrence, biochemistry and possible biotechnological application of the 3-hydroxypropionate cycle.
The 3-hydroxypropionate cycle, a pathway for autotrophic carbon dioxide fixation, is reviewed with special emphasis on the biochemistry of CO2 fixing enzymes in Acidianus brierleyi, a thermophilic and acidophilic archeon. In the 3-hydroxypropionate cycle, two enzymes, acetyl-CoA carboxylase and propionyl-CoA carboxylase, catalyze CO2 fixation. It has been shown in A. brierleyi, and subsequently in Metallosphaera sedula, that acetyl-CoA carboxylase is promiscuous, acting equally well on acetyl-CoA and propionyl-CoA. The subunit structure of the acyl-CoA carboxylase was shown to be alpha4beta4gamma4. Gene cloning revealed that the genes encoding the three subunits are adjacent to each other. accC encodes the beta-subunit (59 kDa subunit, biotin carboxylase subunit), accB encodes the gamma-subunit (20 kDa subunit, biotin carboxyl carrier protein), and pccB encodes the alpha-subunit (62 kDa subunit, carboxyltransferase subunit). Sequence analyses showed that accC and accB are co-transcribed and that pccB is transcribed separately. Potential biotechnological applications for the 3-hydroxypropionate cycle are also presented.
Ishii M, Chuakrut S, Arai H, Igarashi Y. Occurrence, biochemistry and possible biotechnological application of the 3-hydroxypropionate cycle. Appl Microbiol Biotechnol. 2004 Jun;64(5):605-10. Epub 2004 Feb 28.

Krebs cycle

2006-12-20T23:15:00.000-05:00

Above, the TCA cycle – click to enlarge to a legible size. The Krebs, or citric acid cycle is important in aerobic organisms as part of cellular respiration by which carbohydrates, fats, and proteins yield energy, H2O and CO2. Each cycle produces 3 CO2, 4 NADH, 1 FADH2, and 1 ATP from a molecule of pyruvate. Those reactions that converge on the citric acid cycle to 'fill up' intermediates are called anaplerotic reactions.

Following glycolysis, in which glucose is converted to two molecules of the intermediate pyruvate, the TCA cycle is the second of three metabolic pathways involved in catabolism of fuel molecules and ATP production. The third pathway is oxidative phosporylation. Four reactions are classed as anaplerotic, although the production of oxaloacetate from pyruvate is probably the most important physiologically.

The eponymous Krebs cycle is also named the tricarboxylic acid cycle, the TCA cycle, or the citric acid cycle. It is a non catalytic cycle, which signifies that one mole of acetyl CoA requires one mole of oxaloacetate making one mole of citrate which is converted back to one mole of oxaloacetate. Thus, the pathway merely replaces the oxaloacetate initially used, and no matter how much acetyl CoA is fed into the tricarboxylic acid cycle, it is impossible to produce more oxaloacetate, and the ability to oxidize acetyl CoA depends on the availability of oxaloacetate. animation~Krebs :

Bacteria and some species of higher plants are able to obtain a net increase in malate or oxaloacetate through expression of enzymes of the glyoxylate cycle or glyoxylate shunt. Two acetyl CoA are input per glyoxylate cycle with no loss of CO2, making possible net synthesis of a 4-carbon product. The two additional enzymes that permit the glyoxylate shunt are isocitrate lyase and malate synthase.

Table Enzymes Cofactors of Krebs Cycle Enzymes Functions Krebs cycle :

The enzyme pyruvate carboxylase stimulates the TCA cycle by replenishing or increasing the overall available oxaloacetate supply. Because pyruvate dehydrogenase is irreversible, oxaloacetate cannot be synthesized from acetyl CoA. The two enzymes, pyruvate carboxylase and pyruvate dehydrogenase, control the supply of pyruvate, and are themselves reciprocally regulated.

Acetyl CoA activates pyruvate carboxylase and the conversion of pyruvate to oxaloacetate, and inhibits pyruvate dehydrogenase. In addition, pyruvate dehydrogenase is inactivated by a specific protein kinase, and activated by a phosphatase. The phosphatase is sensitive to levels of Ca2+ such that elevated Ca2+ levels increase pyruvate dehydrogenase activity. (Divalent cation concentrations rise in mitochondria when ATP is depleted and is replaced by ADP, since the metal binding affinity of the diphosphate is significantly less than that of the triphosphate.)

NADH and acetyl CoA are activators of the pyruvate dehydrogenase (protein) kinase, which in turn reduces the pyruvate dehydrogenase activity by phosphorylating key serine residues. High energy states favor pyruvate carboxylase by shifting the equilibrium toward CO2 activation, but inhibit pyruvate dehydrogenase, reducing levels of acetyl CoA. Conversely, low energy states favor pyruvate dehydrogenase and increase conversion of pyruvate to acetyl CoA.

Citric acid cycle compounds: Citrate, Isocitrate, alpha-ketoglutarate, succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate: mnemonic: “Citrate is a key substrate for mitochondrial oxidation”

Citrate Cycle Enzymes: Citrate synthatase, aconitase, Isocitrate dehydrogenase, Alpha ketogluturate dehydrogenase, Succinyl CoA synthetase, Succinate dehydrogenase, Fumarase, Malate Dehydrogenase: mnemonic: "Corrupt Anti Intelligence Agent Spoke Slander For Money."

Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants
A case study of endosymbiotic gene transfer. modified: The citric acid or tricarboxylic acid cycle is a central element of higher-plant carbon metabolism which provides, among other things, electrons for oxidative phosporylation in the inner mitochondrial membrane, intermediates for amino-acid biosynthesis, and oxaloacetate for gluconeogenesis from succinate derived from fatty acids via the glyoxylate cycle in glyoxysomes. The tricarboxylic acid cycle is a typical mitochondrial pathway and is widespread among alpha-proteobacteria, the group of eubacteria as defined under rRNA systematics from which mitochondria arose. Most of the enzymes of the tricarboxylic acid cycle are encoded in the nucleus in higher eukaryotes, and several have been previously shown to branch with their homologues from alpha-proteobacteria, indicating that the eukaryotic nuclear genes were acquired from the mitochondrial genome during the course of evolution. Here, we investigate the individual evolutionary histories of all of the enzymes of the tricarboxylic acid cycle and the glyoxylate cycle using protein maximum likelihood phylogenies, focusing on the evolutionary origin of the nuclear-encoded proteins in higher plants. The results indicate that about half of the proteins involved in this eukaryotic pathway are most similar to their alpha-proteobacterial homologues, whereas the remainder are most similar to eubacterial, but not specifically alpha-proteobacterial, homologues. A consideration of (a) the process of lateral gene transfer among free-living prokaryotes and (b) the mechanistics of endosymbiotic (symbiont-to-host) gene transfer reveals that it is unrealistic to expect all nuclear genes that were acquired from the alpha-proteobacterial ancestor of mitochondria to branch specifically with their homologues encoded in the genomes of contemporary alpha-proteobacteria. Rather, even if molecular phylogenetics were to work perfectly (which it does not), then some nuclear-encoded proteins that were acquired from the alpha-proteobacterial ancestor of mitochondria should, in phylogenetic trees, branch with homologues that are no longer found in most alpha-proteobacterial genomes, and some should reside on long branches that reveal affinity to eubacterial rather than archaebacterial homologues, but no particular affinity for any specific eubacterial donor. Schnarrenberger C, Martin W. Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants A case study of endosymbiotic gene transfer. (Free Full Text Article) Eur J Biochem. 2002 Feb;269(3):868-83. FEBS.

methylerythritol phosphate pathway

2006-12-18T19:04:00.000-05:00

The methylerythritol phosphate pathway provides a route to isoprenoid biosynthesis in the plastids of plants, in protozoa, and in prokaryotes. Plants also employ the HMG-CoA-reductase pathway to manufacture isoprenoids - small image, 128 k image.

Isopentenyl diphosphate (IPP) is the fundamental unit in isoprenoid biosynthesis. E. coli utilizes a mevalonate-independent pathway for synthesis of IPP. In the initial step 1-deoxy-D-xylulose 5-phosphate (DXP) is formed by condensation of pyruvate and glyceraldehyde 3-phosphate. In the second step DXP is rearranged and reduced in a single reaction yielding 2-C-methyl-D-erythritol 4-phosphate (MEP). In the third reaction MEP is converted into 4-diphosphocytidyl-2-C-methylerythritol, which is subsequently phosphorylated at the 2 position hydroxy group yielding 4-diphosphocytidyl-2C-methylerythritol 2-phosphate. This product is then converted into 2-C-methyl-D-erythritol 2,4-cyclodiphosphate. [ Takahashi98 , Sprenger97 , Lois98 , Lange98 , Rohmer93 , Luttgen00 , Rohdich99 , Herz00 ] The final two steps are catalyzed by the IspG and IspH proteins, respectively [ Hecht01 , Rohdich02 ] . [source]

In the bacterium Bacillus subtilis, isoprene is not formed by the mevalonate pathway or from catabolism of leucine, but, as in plant systems, it is a product of the methylerythritol phosphate pathway of isoprenoid synthesis.

Two genes encoding the enzymes 1-deoxy-D-xylulose-5-phosphate synthase and 1-deoxy-D-xylulose-5-phosphate reductoisomerase have been recently identified, suggesting that isoprenoid biosynthesis in Plasmodium falciparum depends on the methylerythritol phosphate (MEP) pathway, and that fosmidomycin could inhibit the activity of 1-deoxy-D-xylulose-5-phosphate reductoisomerase. The metabolite 1-deoxy-D-xylulose-5-phosphate is not only an intermediate of the MEP pathway for the biosynthesis of isopentenyl diphosphate but is also involved in the biosynthesis of thiamin (vitamin B1) and pyridoxal (vitamin B6) in plants and many microorganisms. The MEP pathway is functionally active in all intraerythrocytic forms of P. falciparum, demonstrating de novo biosynthesis of pyridoxal in a protozoan. The absence of the MEP pathway and isoprenoid biosynthesis in the human host makes both pathways very attractive as potential new targets for antimalarial drug development.[a]

The MEP pathway is not present in humans and it is involved in the production of phosphate-containing antigens recognized by γ-δ T lymphocytes.

Biosynthetic Routes to the Building Blocks of Isoprenoids pdf : Mycorrhiza Literature Exchange : Plant Biol : Elucidation of the Methylerythritol Phosphate Pathway for Isoprenoid Biosynthesis in Bacteria and Plastids. A ... :

Synonyms: methylerythritol phosphate pathway, nonmevalonate isopentenyl diphosphate biosynthesis, methylerythritol phosphate degradation, MEP degradation, deoxyxylulose phosphate pathway, DXP pathway, Rohmer pathway, isopentenyl diphosphate biosynthesis – mevalonate-independent

Arabidopsis thaliana col , Escherichia coli K-12 , Lycopersicon esculentum

nitrogen assimilation

2006-12-17T23:36:00.000-05:00

oxidative phosporylation

2006-12-16T16:42:00.000-05:00

Oxidative phosphorylation is the ultimate metabolic pathway of cellular respiration, and follows glycolysis and the Krebs cycle. The enzymes of oxidative phosphorylation are membrane-bound – at the plasma membrane of prokaryotes, and the analogous inner mitochondrial membrane of eukaryotes.

Energy sources such as glucose are initially metabolized (glycolysis) in the cytoplasm and the products are imported into mitochondria, which continue catabolic metabolism employing metabolic pathways that include the Krebs cycle (citric acid cycle), beta-oxidation of fatty acids, and oxidation of amino acids.

Tables Enzymes Functions Krebs cycle Enzymes Cofactors of Krebs Cycle Electron Transport vs Oxidative Phosphorylation :

In oxidative phosphorylation, the energy carrier molecules generated by the citric acid cycle (NADH & FADH2) enter an electron transfer chain that generates a proton gradient by pumping protons (H⁺) across the membrane.

Electrons from the donors are passed through an electron transport chain to O2, which is reduced to H2O. This multi-step redox process occurs at the mitochondrial inner membrane. The enzymes that catalyze these reactions simultaneously create a proton gradient across the membrane, producing a thermodynamic high-energy state with the potential to do work. Although electron transport occurs with great efficiency, a small percentage of electrons are prematurely leaked to oxygen, resulting in the formation of the toxic free radical, superoxide.

Intracellular mitochondria are remarkably similar to free-living bacteria. The known structural, functional and DNA similarities between mitochondria and bacteria provide strong evidence that mitochondria evolved from intracellular prokaryotic symbionts that took up residence in primitive eukaryotic cells.

Table Enzymes Functions Krebs cycle Electron Transport Chain vs Oxidative Phosphorylation :

Oxidative phosphorylation metabolic pathway: diagram : Brooks-Cole animation oxidative phosphorylation : Boyer animation oxidative phosphorylation : quick animation ~ electron transport chain in mitochondria : quick animation ~ ATP synthesis in mitochondria : quick animation ~ proton gradient in mitochondria : diagram pseudorotation ATP : animation pseudorotation ATP :

In more detail:
1. Complex I (NADH:ubiquinone oxidoreductase) comprising NADH dehydrogenase and ubiquinone transfers two electrons from NADH to the lipid-soluble carrier, ubiquinone (Q). The reduced product of this redox reaction is ubiquinol (QH2), which is free to diffuse within the membrane. Simultaneous with the reduction of ubiquinone, Complex I moves four protons (H+) across the membrane, generating a proton gradient. Complex I is one of the main sites of production of superoxide free radicals, in which premature electron leakage to oxygen occurs.

The pathway of electrons:
NADH is oxidized to NAD+, reducing FMN to FMNH2 in a single two-electron step. The subsequent electron carrier is a Fe-S cluster, which accepts a single electron to reduce the ferric ion into a ferrous ion. FMNH2 can only be oxidized in two one-electron steps, through a semiquinone intermediate. The electron thus travels from the FMNH2 to the Fe-S cluster, and then from the Fe-S cluster to the oxidized Q to generate the free-radical (semiquinone) form of Q. This reduces the semiquinone form to the ubiquinol form, QH2. Simultaneously, four protons are translocated from the matrix across the inner mitochondrial membrane to the intermembrane space. This generates the proton gradient that will be subsequently used to generate ATP through oxidative phosphorylation.

2. Complex II comprises succinate dehydrogenase, which is not a proton pump. It functions to funnel additional electrons into the quinone pool (Q) by removing electrons from succinate and transferring them (via FAD) to Q. Other electron donors such as fatty acids and glycerol 3-phosphate also funnel electrons into Q (via FAD).

3. Complex III comprises cytochrome bc1 complex and removes two electrons from QH2 and stepwise transfers them to two molecules of cytochrome c, which is a water-soluble electron carrier located on the outer surface of the membrane. Simultaneously, Complex III pumps four protons across the membrane, generating a proton gradient. When electron transfer is hindered (by a high membrane potential, point mutations, or by respiratory inhibitors such as antimycin A), Complex III may leak electrons to O2 resulting in the formation of a superoxide.

4. Complex IV comprises cytochrome c oxidase, which removes four electrons from four molecules of cytochrome c and transfers them to molecular oxygen (O2), producing two molecules of water (H2O). Simultaneously, it pumps four protons across the membrane, generating a proton gradient.

Thus, the electron transport chain comprises four complexes, of which three complexes (I, III, IV) pump protons across the inne mitochondrial membrane to generate a proton gradient that supplies energy to ATP synthase, which generates ATP in oxidative phosphorylation. ATP synthase is sometimes regarded as complex V of the electron transport chain, though strictly it merely follows the chain.

ATP synthase enzymes have been considerably conserved through evolution. The enzymes in bacteria are essentially the same in structure and function as those in the mitochondria of animals, plants and fungi, and the chloroplasts of plants. There are minor differences between bacteria, mitochondria and chloroplasts in some of the smaller subunits, leading to a confusing nomenclature. The simplest ATP sunthase system is that in E. coli.

The early ancestory of the enzyme is observable in the fact that Archaea have an enzyme that is clearly closely related, yet exhibits significant differences from the Eubacterial branch. The H+-ATP-ase found in vacuoles in the cell cytoplasm of eukaryotes is similar to the archaeal enzyme, and this is thought to reflect its origin from an archaeal ancestor.

In most systems, the ATP synthase is embedded in the membrane (the "coupling" membrane), and catalyses the synthesis of ATP from ADP and phosphate, which is driven by a flux of protons across the membrane and down the proton gradient generated by electron transfer. The flux flows from the protochemically positive (P) side with a high proton electrochemical potential to the protochemically negative (N) side. The reaction catalyzed by ATP synthase is fully reversible, so ATP hydrolysis generates a proton gradient by a reversal of this flux. In some bacteria, the chief function of ATP synthase moves in the direction of ATP hydrolysis, employing ATP generated by fermentative metabolism to provide a proton gradient that drives substrate accumulation, and maintains ionic balance.
ADP + Pi + nH+P <=> ATP + nH+N

View ATP Synthase Animation : Animation movies of ATP synthase : Yoshida Hisabori movies : Nature animation ATP synthase : Pictures & Movies : ATP synthesis ~ animation : animation of ATP synthesis :

Table Electron Transport Chain vs Oxidative Phosphorylation Enzymes Functions Krebs cycle :

The reactions catalyzed by Complex I and Complex III operate close to equilibrium, such that the steady-state concentrations of the reactants and products are approximately equal. Thus, these reactions are readily reversible by increasing the concentration of the products relative to the concentration of the reactants (for example, by increasing the proton gradient).
ATP synthase is also readily reversible.

Thus, ATP can be used to generate a proton gradient, which in turn can be employed to generate NADH, which is the reverse of the eukaryotic mechanism that employs NADH as the chief electron donor for the ultimate generation of ATP by oxidative phosphorylation. This process of reverse electron transport is important in many prokaryotic electron transport chains, in which there exist a variety of electron donors and electron acceptors – a variety of dehydrogenases, of oxidases, of reductases, and of electron acceptors:

pentose-phosphate pathway

2006-12-15T23:47:00.000-05:00

The pentose phosphate pathway is primarily a cytoplasmic anabolic pathway that converts the 6 carbons of glucose to 5 carbon (pentose) sugars and reducing equivalents. (diagram) This pathway oxidizes glucose and its products can be completely oxidized to CO2 and water.

The pentose phosphate pathway regenerates NADPH from NADP+ through an oxidation/ reduction reaction that is coupled to the formation of ribose 5-phosphate from glucose 6-phosphate. The pentose phosphate pathway has both oxidative and non-oxidative arms.

Oxidation steps (diagram), utilizing glucose-6-phosphate (G6P) as the substrate, occur at the beginning of the pathway and generate NADPH. These reactions, catalyzed by glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, generate one mole of NADPH each for every mole of glucose-6-phosphate (G6P) that enters the pentose phosphate pathway (PPP).

The non-oxidative reactions (diagram) of the pentose phosphate pathway primarily generate ribose 5-phosphate (R5P). The pentose phosphate pathway also converts dietary 5 carbon sugars into both 6 (fructose-6-phosphate) and 3 (glyceraldehyde-3-phosphate) carbon sugars which can then be utilized by the pathways of glycolysis. The primary enzymes involved in the non-oxidative steps of the PPP are transaldolase and transketolase.

In summary, the pentose phosphate pathway primarily generates NADPH, ribose 5-phosphate, fructose 6-phosphate, and glyceraldehyde 3-phosphate (diagram, diagram). Glyceraldehyde-3-phosphate can be shunted to glycolysis and oxidized to pyruvate. Alternatively, glyceraldehyde-3-phosphate can be utilized by the gluconeogenic enzymes to generate more 6 carbon sugars (fructose-6-phosphate or glucose-6-phosphate).

NADPH is employed in reductive reactions in anabolism, particularly in the synthesis of fatty acids. In red blood cells (erythrocytes), the major role of NADPH is to reduce the disulfide form of glutathione to the sulfhydryl form. Reduced glutathione is important for maintenance of the normal structure of eythrocytes and for maintaining hemoglobin in the ferrous state [Fe(II)]. Deficiency of the oxidative pathway enzyme glucose-6-phosphate dehydrogenase causes hematologic problems because the inability to maintain reduced glutathione results in accumulation of damaging peroxides (H2O2). G6PD-deficiency is associated, however, with resistance to the malarial parasite Plasmodium falciparum because the weakened RBC membrane (erythrocytic host cell) cannot sustain the parasitic life cycle long enough for productive growth.

photorespiration

2006-12-15T23:39:00.000-05:00

phosphorylation

2006-12-15T16:09:00.000-05:00

Phosphorylation involves the addition of a phosphate group (PO4) to a protein or other molecule. Addition of PO4 renders the molecule more polar, and hence hydrophilic, and increases the Gibbs free energy potential of the recipient molecule. Phosphorylation is a very important reaction in cellular regulation, signaling and energy management. ATP synthase is the ultimate enzyme in oxidative phosporylation (table).

Specific protein kinases transfer a phosphate group from a donor such as ATP to amino acid acceptors in proteins, while protein phosphatases remove the phosphate groups that have been attached by protein kinases. Examples are receptor tyrosine kinases (RTKs), cytoplasmic protein tyrosine kinases (PTKs), and serine-threonine kinases.

Autophosphorylation is a property of most protein kinases, in which either serine and/or threonine or tyrosine serves as the phosphoacceptor for phosphorylation of self by a serine-threonine kinases or receptor tyrosine kinase. Several sites on the same kinase subunit are usually autophosphorylated in a manner that affects the functional properties of most protein kinases.[r]

Tables Phosphate-handling Enzymes Cell signaling RTKs

Not to be confused with phosphatases or kinases, phosphorylases are allosteric enzymes that catalyze the transfer of phosphate groups from an inorganic phosphate to an acceptor. Phosporylases are classified according to the acceptor molecule, and all phosphorylases share catalytic and structural properties. For example, glycogen phosphorylase attacks 1,4 glycosidic linkages in linear glycogens to generate glucose-1-phosphate, which is subsequently converted, by phosphoglucomutase (rev. isomutase) , into glucose-6-phosphate for glycolysis or the pentose-phosphate pathway. Debranching enzymes are required to attack 1,6 glycosidic branching points. Several enzymes possess separate phosphorylation sites for the activation or inhibition of functional regulation. For example, a subclass of serine/threonine protein kinases, CDKs can be either activated or deactivated depending upon the specific amino acid residue that is undergoing phosphorylated. Cyclin-dependent kinases (CDKs) play a role in regulation of transcription and in mRNA processing, and in regulation of the cell cycle. Studies with yeast and embryonic cells suggest that mitosis is triggered by the periodic activation of cdc2 kinase (cdk1). This enzyme is a member of the Ser/Thr protein kinase family, and is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins form stable associations with cdk1 (cdc2), and function as regulatory subunits. The kinase activity of cdk1 is controlled by cyclin accumulation and destruction through the cell cycle. The phosphorylation and dephosphorylation of cdk1 play important regulatory roles in cell cycle control.

Adenylyl (adenylate) cyclases are enzymes, which cross the membrane twelve times (right) and which convert ATP to the second-messenger cAMP (3',5' cyclic AMP) and pyrophosphate (below left). Likewise, guanylate cyclases convert GTP to the second messenger, cGMP. Adenylyl cyclases are coincidence detectors, meaning that they are only activated by several different signals occurring together – they are modulated by G-proteins, forskolin, Ca2+/calmodulin, and other class-specific substrates.

Phospholipases are enzymes that hydrolyze specific ester bonds in phosphoglycerides or glycerophosphatidates, converting the phospholipids into fatty acids and other lipophilic substances. Phospholipases are involved in signaling cascades. Phospholipase A1 hydrolyzes the acyl group attached to the 1-position, while phospholipase A2 hydrolyzes the acyl group attached to the 2-position to form fatty acid and lysophospholipid products. Phospholipase A2 is responsible for the release of arachidonic acid from membranes (flow diagram PLA2 pathway). Arachidonic acid is a signalling molecule and is the precursor for eicosanoid signaling molecules, which include leukotrienes and prostaglandins. Some eicosanoids are synthesized from diacylglycerol, and are released from the lipid bilayer by phospholipase C.

Members of the five subtypes of phosphodiesterase enzymes degrade the cyclic nucleotide, second messengers, cAMP and cGDP by hydrolyzing phosphodiester bonds, so they are important in regulation of signal transduction. Phospodiesterase inhibitors, such as caffeine, aminophylline, theophylline and Viagra, prolong or amplify the physiological processes that are mediated by cAMP or cGDP. The phospodiester bond form the linkage between 3'-C of nucleotides and 5'-C of pentose sugars in the backbones of DNA & RNA, rendering phosphodiester bonds particularly important. 3'-phospodiesterase is important in repair of oxidative DNA damage.

Tables Phosphate-handling enzymes Cell signaling RTKs Second Messengers .

Examples of use of phosphorylation/dephosphorylation:
1. signaling networks and signal transduction (two-component system)
2. control of cell cycle
3. regulation of amino acids within Ser > Thr >>>>> Tyr
5. bacterial phosphorylation of the amino acids His and Asp in two-component signaling
6. p53 tumor suppressor gene
7. control of chemotaxis in prokaryotes (two-component system)

Examples of phosphorylation reaction
1. ADP + Pi →ATP synthase→ ATP : during oxidative phosporylation, substrate-level phosphorylation during glycolysis, and PSII light-reactions during noncyclic photophosphorylation (diagram Z-scheme)
2. NADH + Pi→NADPH in catabolic reactions such as photophosphorylation

Examples of dephosphorylation reaction
1. ATP - Pi → ADP in anabolic reactions
2. NADPH -Pi →NADH in anabolic reactions

Examples of signaling phosphorylation/dephosphorylation enzymes: two-component systems :
1. receptor tyrosine kinases (RTKs)
2. protein tyrosine phosphatases (PTPs) - transmembrane and intracellular - (CD45),
3. serine/threonine kinases (activins, inhibins, bone morphogenetic proteins (BMPs), MAP kinases, PKCs, TGF-beta receptors),
4. cAMP dependent protein kinase (Phospholipases (PLD, PLA2), Phosphatidylinositol-3-Kinase,
6. Phosphatases.

The spatio-temporal activation of protein kinases and phosphatases is an important factor in controlling where and when phosphorylation events occur. Anchoring proteins provide a molecular framework that orients these enzymes towards selected substrates. A-kinase anchoring proteins (AKAPs) are signal-organizing molecules that compartmentalize the cAMP dependent protein kinase, phosphodiesterases, and a variety of enzymes that are regulated by second messengers[s].

Phospholipases and phospholipids participate in transmission of ligand-receptor induced signals from the plasma membrane to intracellular proteins, primarily PKC, which is maximally active in the presence of calcium ion and diacylglycerol. PKC activity is mediated by receptors that are coupled to activation of phospholipase C-gamma (PLC-gamma), which contains SH2 domains that enable it to interact with tyrosine phosphorylated RTKs. PI-3K is tyrosine phosphorylated and activated by various RTKs and receptor-associated PTKs. PI-3K is activated by the PDGF, EGF, insulin, IGF-1, HGF and NGF receptors. The p85 subunit of PI-3K is activated by tyrosine phosphorylation, but only the 110 kDa subunit is enzymatically active.

Phospholipases D and A2 (PLD, PLA2) sustain the activation of PKC through their hydrolysis of membrane phosphatidylcholine (PC). Activation of PLC-gamma results in hydrolysis of membrane phosphatidylinositol bisphosphate (PIP2), which leads to an elevation of intracellular second messengers, diacylglycerol (DAG) and inositol trisphosphate (IP3), which interact with intracellular membrane receptors to effect release of stored calcium ions (PKC is maximally active in the presence of calcium ion and diacylglycerol).

Chemotaxis • hormones • neurotransmission • Nitric Oxide • neuronal interconnections • phosphotransfer-mediated signaling pathways • Protein Kinase Signaling Networks • protein tyrosine kinases, PTKs • receptor tyrosine kinases • Receptor Tyrosine Kinases (RTKs) • serine/threonine kinases • signaling gradients • signal transduction • two-component systems • animation MAPK signal transduction :

Signaling pathways:
Pathways ABC transporters : Phosphotransferase system (PTS) : Two-component system : MAPK signaling pathway : Wnt signaling pathway : Notch signaling pathway : Hedgehog signaling pathway : TGF-beta signaling pathway : VEGF signaling pathway : Jak-STAT signaling pathway : Calcium signaling pathway : Phosphatidylinositol signaling system : mTOR signaling pathway : Neuroactive ligand-receptor interaction : Cytokine-cytokine receptor interaction : ECM-receptor interaction : Cell adhesion molecules (CAMs) : Orthologies Transporters (+diseases) : Two-component system : Receptors and channels (+diseases) : Cytokines : Cell adhesion molecules (CAMs) : CAM ligands : CD molecules : GTP-binding proteins :

pyruvate dehydrogenase reaction

2006-12-15T01:06:00.000-05:00

The pyruvate dehydrogenase reaction brings about conversion of pyruvate into acetyl-CoA . The reaction is catalyzed by an enzyme-complex incorporating the allosteric enzyme pyruvate dehydrogenase (PDC).

PDC constitution
The components of PDC are species dependent. The E.coli complex comprises 60 subunits: 24 of pyruvate dehydrogenase, 24 of dihydrolipoyl transacetylase, and 12 of dihydrolipoyl dehydrogenase (often denoted E1, E2, and E3).

E1: 24 molecules of pyruvate dehydrogenase incorporates the coenzyme TPP (thiamin pyrophosphate).
E2: 24 dihydrolipoyl transacetylase incorporates lipoate and coenzyme A.
E3: 12 dihydrolipoyl dehydrogenase incorporates the coenzymes FAD and NAD+.

In contrast to E.coli, eukaryotes and gram-positive bacteria such as Bacillus stearothermophilus have a central PDC core that contains 60 E2 molecules arranged into an icosahedron. Eukaryotes also contain 12 copies of an additional core protein, E3 binding protein (E3BP). (more detail)

Cofactors
The PDC comples utilizes 5 different cofactors, of which multiple copies may be required:
1. TPP (Thiamine pyrophosphate) - Hydroxyethyl Carrier
2. CoA (Coenzyme A) - Substituted onto the Acetyl group to form Acetyl-CoA
3. R-Lipoic acid - Utilized as a Lysine Tether to transport Acetyl group to acitve site for CoA addition
4. FAD (Flavin Adenine Dinucleotide) - Oxidizing agent to oxidize the lipoyllysine sulfaring to repeat process.
5. NAD (Nicotinamide adenine dinucleotide)- Oxidizes FADH2 in order to repeat process. NADH is then used for oxidative phosphorylation or may be used somewhere else in the cytosol.

Reaction of PDC
Pyruvate is decarboxylated in a complex reaction and converted into acetaldehyde, then attached to coenzyme A while NAD+ is subsequently reduced to NADH and H+:

Pyruvate + Coenzyme A + NAD⁺ ⇒ acetyl-CoA + NADH + H⁺ + CO2

Regulation of PDC
Pyruvate dehydrogenase is inhibited by increase in any of the ratios : ATP/ADP, NADH/NAD+ and acetyl-CoA/CoASH.

In eukaryotes, PDC is tightly regulated by its own specific PDC kinase (PDK) and a by specific phosphatase (PDP). PDK phosphorylates three specific lysine residues with different affinities on E1. Phosphorylation of any one of the Lys residues inactivates E1 (and in consequence the entire complex). Dephosphorylation of E1 by the phosphatase (PDP) reinstates activity of the PDC complex.

reductive acetyl CoA pathway

2006-12-13T19:42:00.000-05:00

Unlike the reverse tricarboxyclic acid cycle (rTCA), the 3-hydroxypropionate cycle, and the Calvin cycle (RuBP), the reductive acetyl CoA pathway (rACA) is a noncyclic pathway.

The path has both a methyl and carbonyl component. One CO2 is captured on a special tetrahydrofolate cofactor and reduced to a methyl group. The other CO2 is reduced to a carbonyl group (C=O) by carbon monoxide dehydrogenase, and this enzyme-bound carbonyl group is combined with the methyl group to form acetyl CoA by a collection of enzymes termed the acetyl CoA synthase complex. The pathway seems to require hydrogen gas as the electron donor and it is very efficient, requiring only 4H2 per acetate formed.

Organisms that employ rACA include acetogens, which are microbes that generate acetic acid from hydrogen (Clostridium thermoaceticum, Acetobacterium woodii), methanogens (Methanobacterium thermoautotrophicum) and most autotrophic sulfate reducers (Defulfobacterium autotrophicum).

Table ~ Comparison Photosynthesis Respiration : Table ~ Comparison Plant Bacterial Photosynthesis : Table ~ comparison of C-3, C-4, CAM plants : Table ~ Photosynthesis Overview : Microtextbook Carbon Assimilation ::: image_Calvin cycle : image_reductive tricarboxylic acid cycle : image_reductive CoEnzymeA cycle : image_3-hydroxypropionate cycle :: Saccharomyces cerevisiae carbon monoxide dehydrogenase pathway : Arabidopsis thaliana carbon monoxide dehydrogenase pathway : MetaCyc reductive acetyl coenzyme A pathway :

respiratory burst

2006-12-13T19:40:00.000-05:00

During phagocytosis the phagocytic cell undergoes an increase in glucose and oxygen consumption termed the respiratory burst. The respiratory burst generates several oxygen-containing compounds that kill the bacteria uncergoing phagocytosis – oxygen-dependent intracellular killing. Bacteria can also be killed by pre-formed substances released from granules or lysosomes upon bacterial fusion with the phagosome – oxygen-independent intracellular killing.

1. Oxygen-dependent myeloperoxidase-independent intracellular killing.
During phagocytosis, glucose is metabolized via the pentose monophosphate shunt, with formation of NADPH. Cytochrome B from the granulocyte-specific granule combines with and activates plasma membrane NADPH oxidase. The activated NADPH oxidase then employs oxygen to oxidize the formed NADPH with resultant production of superoxide anion. A portion of the superoxide anion is converted to H2O2 plus singlet oxygen by superoxide dismutase. Additionally, superoxide anion can react with H2O2, resulting in the formation of hydroxyl radical plus more singlet oxygen. Together these reactions produce the toxic oxygen compounds superoxide anion (O2-), H2O2, singlet oxygen (1O2) and hydroxyl radical (OH•).

2. Oxygen-dependent myeloperoxidase-dependent intracellular killing
Fusion of azurophilic granules with the phagosome causes release of myeloperoxidase into the phagolysosome. Myeloperoxidase utilizes H2O2 and halide ions (usually Cl-) to produce highly toxic hypochlorite. Some hypochlorite spontaneously breaks down to yield singlet oxygen. Together these reactions produce toxic hypochlorite (OCl-) and singlet oxygen (1O2).

3. Detoxification reactions

Neutrophils and macrophages are able to protect themselves by detoxifying the toxic oxygen intermediates that they generate. Granulocyte self-protection is achieved in reactions employing the dismutation of superoxide anion to hydrogen peroxide by superoxide dismutase and the conversion of hydrogen peroxide to water by catalase.

reverse tricarboxyclic acid cycle

2006-12-13T19:03:00.000-05:00

The reductive tricarboxylic acid cycle provides an alternative strategy to the Calvin cycle for fixing CO2 by reversing the TCA cycle. Rather than breaking down acetyl CoA with the release of 2 CO2 and the generation of energy, acetyl CoA is synthesized by the incorporation of 2 CO2 and the input of 8 H (in the form of NADH and/or FADH), plus 2 ATP.

Some of the enzymes in the pathway are identical to the TCA cycle, but many of the energy requiring reactions are catalyzed by different enzymes. ATP citrate lyase is a key enzyme that cleaves citrate (6 carbons) into oxaloacetate (4 carbons) and acetyl CoA (2 carbons).

Green photosynthetic bacteria (Chlorobium limicola), some thermophillic bacteria that grow on hydrogen, (Hydrogenobacter thermophilus) and certain bacteria that grow by reducing sulfate (Desulfobacter hydrogenophilus ) have been shown to use rTCA.

Table ~ Comparison Photosynthesis Respiration : Table ~ Comparison Plant Bacterial Photosynthesis : Table ~ comparison of C-3, C-4, CAM plants : Table ~ Photosynthesis Overview : Microtextbook Carbon Assimilation ::: image_Calvin cycle : image_reductive tricarboxylic acid cycle : image_reductive CoEnzymeA cycle : image_3-hydroxypropionate cycle :: Saccharomyces cerevisiae carbon monoxide dehydrogenase pathway : Arabidopsis thaliana carbon monoxide dehydrogenase pathway : MetaCyc reductive acetyl coenzyme A pathway :

"The reverse tricarboxylic acid (rTCA) cycle is an alternative CO2 fixation pathway that generates a stable isotopic signature more closely resembling "primary consumers from a number of hydrothermal vent sites" (37, 44). To date, the rTCA cycle has been found in only a few microorganisms, including Chlorobium species, a few members of the delta subdivision of Proteobacteria (i.e., Desulfobacter hydrogenophilus), and some members of the thermophilic Aquificales order and archaeal Thermoproteaceae family (5, 13, 15, 19, 27, 42, 43). A reversal of the entire TCA cycle for carbon dioxide fixation uses four or five ATP molecules and generates one molecule of oxaloacetate from four molecules of CO2 (18). Key enzymes of the rTCA cycle include ATP citrate lyase (encoded by the aclBA gene) and two of the four carbon dioxide-fixing enzymes, 2-oxoglutarate:ferredoxin oxidoreductase (encoded by the oorDABC gene), and pyruvate:ferredoxin oxidoreductase (encoded by the porCDAB or nifJ gene). These enzymes catalyze the reversal of the TCA cycle by making the energetically unfavorable reverse reactions possible. For example, ATP citrate lyase catalyzes the cleavage of citrate into acetyl coenzyme A (acetyl-CoA) and oxaloacetate in a CoA- and ATP-dependent matter (2). Reversal of the TCA cycle requires the combined use of all three enzymes for reductive carboxylation to occur.

Recent molecular and isotopic data indicate that the epsilon proteobacterial community associated with Alvinella pompejana, which thrives on the sides of the hotter black smoker chimneys at deep-sea hydrothermal vents, may utilize the rTCA cycle for autotrophic growth. Two of the key genes were present and expressed in the episymbiont community, which is dominated by members of the epsilon subdivision of Proteobacteria (7). In addition, there is genetic evidence of the rTCA cycle in at least two cultured autotrophic members of the epsilon subdivision of Proteobacteria from hydrothermal vents and one autotrophic member of the epsilon subdivision of Proteobacteria isolated from marine sediments (6, 56). Interestingly, molecular studies indicate that members of the epsilon subdivision of Proteobacteria dominate all free-living deep-sea hydrothermal vent microbial environments studied so far (10, 23, 35, 39). Enrichment of a diverse array of chemoautotrophic members of the epsilon subdivision of Proteobacteria from hydrothermal vents further supports the results of these molecular studies (1, 6, 33, 46). These chemoautotrophs utilized H2 or reduced sulfur compounds as electron donors and O2, nitrate, or elemental sulfur as electron acceptors." from:

Abundance of Reverse Tricarboxylic Acid Cycle Genes in Free-Living Microorganisms at Deep-Sea Hydrothermal Vents.
Since the discovery of hydrothermal vents more than 25 years ago, the Calvin-Bassham-Benson (Calvin) cycle has been considered the principal carbon fixation pathway in this microbe-based ecosystem. However, on the basis of recent molecular data of cultured free-living and noncultured episymbiotic members of the epsilon subdivision of Proteobacteria and earlier carbon isotope data of primary consumers, an alternative autotrophic pathway may predominate. Here, genetic and culture-based approaches demonstrated the abundance of reverse tricarboxylic acid cycle genes compared to the abundance of Calvin cycle genes in microbial communities from two geographically distinct deep-sea hydrothermal vents. PCR with degenerate primers for three key genes in the reverse tricarboxylic acid cycle and form I and form II of ribulose 1,5-bisphosphate carboxylase/oxygenase (Calvin cycle marker gene) were utilized to demonstrate the abundance of the reverse tricarboxylic acid cycle genes in diverse vent samples. These genes were also expressed in at least one chimney sample. Diversity, similarity matrix, and phylogenetic analyses of cloned samples and amplified gene products from autotrophic enrichment cultures suggest that the majority of autotrophs that utilize the reverse tricarboxylic acid cycle are members of the epsilon subdivision of Proteobacteria. These results parallel the results of previously published molecular surveys of 16S rRNA genes, demonstrating the dominance of members of the epsilon subdivision of Proteobacteria in free-living hydrothermal vent communities. Members of the epsilon subdivision of Proteobacteria are also ubiquitous in many other microaerophilic to anaerobic sulfidic environments, such as the deep subsurface. Therefore, the reverse tricarboxylic acid cycle may be a major autotrophic pathway in these environments and significantly contribute to global autotrophic processes.
Barbara J. Campbell, and S. Craig Cary, Abundance of Reverse Tricarboxylic Acid Cycle Genes in Free-Living Microorganisms at Deep-Sea Hydrothermal Vents (Free Full Text Article). Appl Environ Microbiol. 2004 October; 70(10): 6282–6289.

lipid synthesis

2006-12-13T15:08:00.000-05:00

: biosynthesis of membrane components :

sulfur metabolism

2006-12-12T23:07:00.000-05:00

urea cycle

2006-12-10T23:15:00.000-05:00

chloroplast

2006-11-22T16:12:00.000-05:00

The chloroplast is the site of photosynthesis in eukaryotic cells, and is the site of the Calvin cycle just as the mitochondrion is the site of oxidative phosphorylation.

The thylakoid membrane, with its embedded photosystems, is the structural unit of photosynthesis. Both photosynthetic prokaryotes and eukaryotes possess membranes with embedded photosynthetic pigments. Only eukaryotes, which have a nuclear membrane and membrane-bound organelles, possess chloroplasts with an encapsulating membrane. The chloroplast has three compartments, while the mitochondrion has only two. Compartments within a chloroplast are the intermembranous space [3], the stroma [6], and the thylakoid lumen (8) within stromal and granal thylokoids [4,5].

1. outer membrane
2. inner membrane
3. intermembranous space
4. stromal thylakoid
5. granal thylakoid
6. stroma (cytosol)
7. granum (a stack of thylakoids)
8. internal lumen of granal and stromal thylakoids
(click to enlarge image)

The typical higher plant chloroplast is lenticular and approximately 5 microns at its largest dimension. Plant cells contain from 1 to 100 chloroplasts, depending on the type of cell. The mature chloroplast is typically bounded by outer (1) and inner (2) membranes that possess significantly different chemical constituents. In addition to enzymes that function in photosynthesis, chloroplasts also contain a circular DNA molecule and the protein-synthetic machinery characteristic of prokaryotes.

Each chloroplast contains about 40 to 80 grana (7), and each grana comprises about 5 to 30 thylakoids. The thylakoids are membranous disks about .25 to .8 microns in diameter, which contain protein complexes, pigments, and other accessory components. The phospholipid bilayer of the thylakoid is folded repeatedly into stacks of grana. (details) These stacks are connect by channels to form a single functional compartment.

The smooth outer membrane (1) is freely permeable to molecules, and resembles the chemical constitution of the eukaryotic plasma membrane. The smooth inner membrane (2) contains many integral transporter proteins that regulate the passage of small molecules like sugars, and proteins (synthesized in the cytoplasm of the cell, but utilized within the chloroplast). The inner membrane chemically resembles prokaryotic cell membranes.

The thylakoid is the site of oxygenic photosynthesis in eukaryotic plants and algae, and in prokaryotic Cyanobacteria. Cyanobacteria possess thylakoid membranes, but as prokaryotes they do not contain chloroplasts. Chlorophyll, accessory pigments, and other integral membrane proteins transduce light energy to provide excited electrons (excitons) to electron transport chains, powering the formation of NADPH and ATP during photophosphorylation.

The folded thylakoid membranes perform the light reactions of photosynthesis utilizing Photosystems I and II, both of which include chlorophyll and carotenoid molecules (bsim - chlorophyll, spfim - chlorophyll, bsim - carotenoid). The reaction center chlorophyll molecule within the antenna of photosystem I responds most strongly to 700 nm light, and is therefore termed P700. The reaction center within the antenna of photosystem II responds most to 680 nm light, and is accordingly called P680.

Photosystem I evolved very early, and it is found in nonoxygenic phototrophs; photosystem II evolved later. Because the PSII photosystem is most sensitive to shorter wavelength 680 nm light, it absorbs slightly more energy than the P700-PSI system.

The electron transport system of each photosystem is embedded within the thylakoid membrane and functions in the production of ATP. The system comprises membrane-bound electron carriers that pass electrons from one molecule to the next. The purple bacteria utilize only one photosystem (PSI), while oxygenic phototrophs utilize two photosystems (PSI and PSII). The photosynthetic machinery of nonoxygenic photosynthetic purple bacteria is often located in intracytoplasmic membranes. It is not yet known whether or not these membranes are similar to the thylakoid membrane of oxygenic phototrophs, or whether these intracytoplasmic membranes of nonoxygenic phototrophs are merely an extension of the plasma membrane.

As intracellular plant organelles, chloroplasts are classified as plastids. Chloroplasts originate within the eukaryotic photosynthetic cell either by division of pre-existing plastids or from protoplastids (proplastid). These proplastids are organelles with little internal structure, enclosed within two dissimilar membranes. It is assumed that thylakoid membranes formed during the chloroplast maturation process and are derived from the inner membrane of the proplastid and chloroplast. diag - chloroplast development

The current consensus is that chloroplasts originated from Cyanobacteria that have become endosymbionts. This is an origin analogous to the endosymbiotic origin of mitochondria, which are believed derived from "purple bacteria", alpha-proteobacteria most closely related to Rickettsiales.

ghrelin, leptin, melanocortin, obestatin

2005-11-13T13:42:00.000-05:00

STANFORD SCIENTISTS' DISCOVERY OF HORMONE OFFERS HOPE FOR OBESITY DRUG - Office of Communications & Public Affairs - Stanford University School of Medicine: "There are several known pathways that regulate body weight: ghrelin, leptin and melanocortin"

internal

2004-10-10T18:52:00.000-04:00

• beta-oxidation • Calvin cycle • choline-folate-methionine • glycolysis • HMG-CoA-reductase pathway • Krebs cycle • nitrogen assimilation • oxidative phosporylation • pentose-phosphate pathway • photorespiration • sulfur metabolism • urea cycle • chloroplast • ghrelin, leptin, melanocortin, obestatin

http://krebbing.blogspot.com/2006/12/sulfur-metabolism.html

o

1990-01-01T01:00:00.001-05:00

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