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TCA cycle VIII (metazoan)

General Background The TCA tricarboxylic acid cycle is a pathway of aerobic respiration that generates both energy and reducing power. It can also generate precursors for various biosynthetic pathways. The pathway is common, and a variation of it exists in all aerobic organisms |CITS: [16746397][16746585][16747930]|. The TCA cycle is so named because the first step in the pathway is the condensation of acetyl-coA to |FRAME: CIT citrate|, an acid with three carboxylate groups. The cycle is also known as the citric acid cycle, the Szent-Gyorgyi-Krebs cycle and the Krebs cycle, named after the scientists who first described it. The input to the cycle is |FRAME: ACETYL-COA acetyl-CoA|, an activated form of |FRAME: ACET acetate| that is generated by the degradation of carbohydrates, fats and proteins. A common source of acetyl-coA is |FRAME: PYRUVATE pyruvate|, which is generated by |FRAME: PWY66-400 glycolysis| and converted to acetyl-CoA by the |FRAME: PYRUVDEHYD-PWY "pyruvate dehydrogenase complex"|. One turn of the cycle in eukaryotes produces 3 molecules of |FRAME: NADH NADH|, one molecule of |FRAME: Reduced-Quinones quinol| and 2 molecules of |FRAME: CARBON-DIOXIDE CO2|. The reduced molecules of NADH and quinol serve as electron donors for oxidative phosphorylation. As electrons flow throught the electron transport chain to a terminal acceptor, protons are pumped across the inner mitochondrial membrane generating a proton motive force (PMF). When the protons return to the mitochondrial matrix, they power ATP synthase which phosphorylates ADP to ATP. The total energy gained from the catabolism of one molecule of glucose by glycolysis, the TCA cycle, and oxidative phosphorylation is about 30 ATP molecules in eukaryotes. About This Pathway There are several differences between the mammalian TCA cycle, which is described here, and the TCA cycles that occur in prokaryotes (the most common of which is described in |FRAME:TCA TCA cycle I (prokaryotic)|. While the prokaryotic pathway utilizes only one, ATP-dependent enzyme to catalyze the interconversion of |FRAME: SUC-COA succinyl-CoA| with |FRAME: SUC succinate|, the mammalian TCA cycle utilizes two isoforms, |FRAME: CPLX66-14 (GDP-forming) succinate-CoA ligase| and |FRAME: CPLX-7862 (ADP-forming) succinyl-CoA ligase|. The level of utilization of each isoform is tissue dependent |CITS: [15234968]|. Another difference concerns isocitrate dehydrogenase. The mammalian |FRAME: CPLX66-11 "isocitrate dehydrogenase"| (|FRAME: EC- "EC"|) uses NAD+ as a cofactor, as opposed to the prokaryotic NADP+-dependent enzyme (|FRAME: EC- "EC"|). Mammals do possess an NADP+-dependent isozyme, but it is used in glutamate biosynthesis and does not participate in the TCA cycle |CITS: [2198251]|. The conversion of |FRAME: MAL (S)-malate| to |FRAME: OXALACETIC_ACID oxaloacetate| is catalyzed in mammals by an NAD+-dependent |FRAME: HS07366-MONOMER "malate dehydrogenase"| (|FRAME: EC- "EC"|). In some prokaryotic organisms this step of the cycle is catalyzed by an NADP+-dependent |FRAME: EG12069-MONOMER malate:quinone oxidoreductase| (|FRAME: EC- "EC"|). Flux through the cycle is regulated on many different levels. Although |FRAME: CPLX66-272 pyruvate dehydrogenase complex| is not a component of the cycle, it plays a pivotal role in determining TCA cycle flux |CITS: [Salway]|. |FRAME: CPLX-7863 "Citrate synthase"|, |FRAME: CPLX66-11 isocitrate dehydrogenase (NAD)| and |FRAME: CPLX66-42 2-ketoglutarate dehydrogenase complex| are other major regulators of the cycle. At the protein modification level, lysine acetylation of enzymes controls cycle activity |CITS: [20167786]|.

from BIOCYC source record: META_PWY66-398
Type: pathway
Taxonomic scope
conserved biosystem

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