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TCA cycle cross products (also known as “nothing is simple” My textbook of choice has been Biochemistry,by Abeles, Frey, and Jencks (Jones and Bartlett, 1992), a text that has a more mechanistic slant (from Jencks) Before we get to the actual cycle, pyruvate (from glycolysis) is first converted into acetyl-CoA by the pyruvate dehydrogenase complex: pyruvate + NAD + CoASH == Acetyl-COA + CO2+ NADH This is multistep reaction carried out by a large complex; Reactome breaks this down into 5 steps. (a) (b) (c) (d) (e) pyruvate + TPP => 2-(alpha-hydroxyethyl)-TPP + CO2 REACT_466.2 2-(alpha-hydroxyethyl)-TPP + lipoamide => S-acetyldihydrolipoamide + TPP REACT_1449.1 S-acetyldihydrolipoamide + CoA => acetyl-CoA + dihydrolipoamide REACT_1323.1 dihydrolipoamide + FAD => lipoamide + FADH2 [pyruvate dehydrogenase] REACT_601.1 FADH2 + NAD+ => FAD + NADH + H+ [pyruvate dehydrogenase] REACT_1397.1 This is multistep reaction carried out by a large complex; Reactome breaks this down into several steps. GO:0050243 has NADP+ I have at least 4 textbooks in front of me indicating that this reaction uses NAD, not NADP. But, I see a lot of papers indicating NADP; So, I suggest the def be altered to pyruvate + NAD/NADP + CoASH==Acetyl-CoA +CO2+NADPH GO:0004738 has no reaction:appears to be a place holder Anyways, GO term: tricarboxylic acid cycle Synonym: citric acid cycle Synonym: Krebs cycle Synonym: TCA cycle GO id: GO:0006099 Definition: A nearly universal metabolic pathway in which the acetyl group of acetyl coenzyme A is effectively oxidized to two C02 and four pairs of electrons are transferred to coenzymes. The acetyl group combines with oxaloacetate to form citrate, which undergoes successive transformations to isocitrate, 2-oxoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate again, thus completing the cycle. In eukaryotes the tricarboxylic acid is confined to the mitochondria. See also glyoxylate cycle. ATTENTION! This term has child, O term: reductive tricarboxylic acid cycle Synonym: reductive carboxylate cycle Synonym: reductive carboxylic acid cycle Synonym: reductive citric acid pathway Synonym: reductive Kreb's cycle Synonym: reductive TCA cycle GO id: GO:0019643 Definition: A pathway leading to the fixation of two molecules of CO2 and the production of one molecule of acetyl-CoA; essentially the oxidative TCA cycle running in reverse. Acetyl-CoA is reductively carboxylated to pyruvate, from which all other central metabolites can be formed. Most of the enzymes of reductive and oxidative TCA cycle are shared, with the exception of three key enzymes that allow the cycle to run in reverse: ATP citrate lyase, 2-oxoglutarate:ferredoxin oxidoreductase, and fumarate reductase. 2-oxoglutarate:ferredoxin oxidoreductase catalyzes the carboxylation of succinyl-CoA to 2-oxoglutarate, ATP citrate lyase the ATP-dependent cleavage of citrate to acetyl-CoA and oxaloacetate, and fumarate reductase the reduction of fumarate forming succinate. Because this uses different enzymes for certain steps, I do not think this should be a child of TCA, but a sib of THE TCA cycle. It's strictly not a reverse of THE TCA cycle. I only consider the “forward” TCA cycle in what follows. The cycle has 8 or 9 steps (depending on textbook), but 14 reactions. Step 1.5 consists of 5 carried out by a large alpha-ketoglutaric acid dehydrogenase complex, analogous to the pyruvate dehydrogenase complex above. 1. TCA cycle part1:CO2 production 1. condensation of oxaloaceate + acetyl-CoA to give citric acid (citrate); GO:0004108, citrate (Si)-synthase activity, REACT_1282.2 , Acetyl-CoA + H2O + Oxaloacetate => Citrate + CoA 2. change citrate to isocitrate using GO:0003994, aconitate hydratase activity (water off, water on), REACT_1898.2 Citrate <=> cis-Aconitate + H2O; REACT_1898.2,cis-Aconitate + H2O <=> Isocitrate 3. oxidize isocitrate to oxalosuccinate (NAD) GO:0004449, isocitrate dehydrogenase (NAD+) activity1 REACT_1068.2 Isocitrate + NAD+ => alpha-ketoglutarate + CO2 + NADH + H+ 4. decarboxylate oxalosuccinate to make alpha-ketoglutaric acid (glutarate)2 5. 3 decarboxylate alpha ketoglutarate (and condense acetyl-CoA) to give succinyl- CoA,REACT_140.2 . This is very complex; catalyzed by an entire complex: 1. 4 alpha-ketoglutarate + TPP => 3-carboxy-1-hydroxypropyl-TPP + CO2 ;REACT_1137.1; 2. 3-carboxy-1-hydroxypropyl-TPP + lipoamide => S-succinyldihydrolipoamide + TPP REACT_1085.1; 3. S-succinyldihydrolipoamide + CoA => succinyl-CoA + dihydrolipoamide REACT_248.1 1 There is also GO:0004450, isocitrate dehydrogenase (NADP+) activity 2 Isocitrate dehydrogenase catalyzes both 1.3 and1.4 Reactome combines 1.3 and1.4 into one reaction, with oxalosuccinate as in intermediate. 3 From Reactome:The conversion of alpha-ketoglutarate (2-oxoglutarate) to succinyl-CoA exactly parallels that for the oxidative decarboxylation of pyruvate to acetyl CoA. The pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes are structurally homologous, containing homologous E1 and E2 proteins, and identical E3 proteins and cofactors. 4 GO:0004591, oxoglutarate dehydrogenase (succinyl-transferring) activity,appear to include step 1.5.1 and 1.5.2 4. dihydrolipoamide + FAD => lipoamide + FADH2 [alpha-ketoglutarate dehydrogenase] REACT_2087.2; GO:0004148 dihydrolipoyl dehydrogenase activity 5. FADH2 + NAD+ => FAD + NADH + H+ [alpha-ketoglutarate dehydrogenase]R REACT_140.2, GO:0004148, dihydrolipoyl dehydrogenase activity 2. TCA cycle part2: Regeneration of Oxaloacetate 1. Get rid of the CoA to give succinate (succinic acid) + GTP5; GO:0004776, succinate-CoA ligase (GDP-forming) activity REACT_337.1 GDP + Orthophosphate + Succinyl-CoA <=> GTP + Succinate + CoA 2. Oxidize succinate to fumarate (using FAD); Succinate <=> Fumarate (with FAD redox reaction on enzyme); REACT_1667.3; GO:0000104, succinate dehydrogenase activity 3. Add water to fumarate to give L-malate; REACT_1656.2; Fumarate + H2O <=> (S)-Malate; GO:0004333, fumarate hydratase activity 4. oxididize malate to oxaloacetate (NAD). ; REACT_2172.2; (S)-Malate + NAD+ <=> Oxaloacetate + NADH + H+; Go to Part 1.1; GO:0030060, activity (has several sibs, all children of L-malate dehydrogenase GO:0016615.malate dehydrogenase activity. however, GO:0030060 is the one for TCA cycle 5 There is also GO:0004775, succinate-CoA ligase (ADP-forming) activity; ADP + Orthophosphate + Succinyl-CoA <=> ATP + Succinate + CoA; REACT_629.1 both can contribute; Both are children of GO:0004774, succinate-CoA ligase activity