Reactome | CS acetylates OA to citrate

CS acetylates OA to citrate

Stable Identifier

R-HSA-70975

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

Synonyms

acetyl-CoA + H2O + oxaloacetate => citrate + CoA + H(+)

ReviewStatus

5/5

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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