CS acetylates OA to citrate

Stable Identifier
Reaction [transition]
Homo sapiens
acetyl-CoA + H2O + oxaloacetate => citrate + CoA + H(+)
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Mitochondrial citrate synthase (CS) dimer catalyzes the irreversible reaction of acetyl-CoA, water, and oxaloacetate to form citrate and coenzyme A. This reaction is the entry point of two-carbon units into the citric acid cycle. The reaction is subject to allosteric regulation. Most of the time, CS is trimethylated on Lys-395 which attenuates its enzymatic activity (Malecki et al. 2017). The gene encoding the human enzyme has been cloned (Goldenthal et al. 1998), but the enzyme has not been characterized in detail. Its properties are inferred from those of the well-studied homologous pig enzyme (e.g., Morgunov and Srere 1998).

CS dimer, malate dehydrogenase MDH2, and aconitase ACO2 form a multienzyme complex ("metabolon") that optimally channels the substrate flow between them (Fahien & Kmiotek, 1983; Wu & Minteer, 2014; Omini et al., 2021).
Literature References
PubMed ID Title Journal Year
9809442 Cloning and molecular analysis of the human citrate synthase gene

Marin-Garcia, J, Ananthakrishnan, R, Goldenthal, MJ

Genome 1998
6824331 Complexes between mitochondrial enzymes and either citrate synthase or glutamate dehydrogenase

Kmiotek, E, Fahien, LA

Arch Biochem Biophys 1983
34548590 Association of the malate dehydrogenase-citrate synthase metabolon is modulated by intermediates of the Krebs tricarboxylic acid cycle

Obata, T, Skirycz, A, Omini, J, Wojciechowska, I, Moriyama, H

Sci Rep 2021
9792662 Interaction between citrate synthase and malate dehydrogenase. Substrate channeling of oxaloacetate

Morgunov, I, Srere, PA

J Biol Chem 1998
28887308 Uncovering human METTL12 as a mitochondrial methyltransferase that modulates citrate synthase activity through metabolite-sensitive lysine methylation

Jakobsson, ME, Falnes, PØ, Małecki, J, Rustan, AC, Moen, A, Ho, AYY

J Biol Chem 2017
25537779 Krebs cycle metabolon: structural evidence of substrate channeling revealed by cross-linking and mass spectrometry

Minteer, S, Wu, F

Angew Chem Int Ed Engl 2015
Catalyst Activity

citrate (Si)-synthase activity of N6,N6,N6-trimethyl-K395-CS dimer [mitochondrial matrix]

Orthologous Events
Cross References
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