acetyl-CoA + bicarbonate + ATP => malonyl-CoA + H2O + ADP + orthophosphate

Stable Identifier
Reaction [transition]
Homo sapiens
Formation of Malonyl-CoA from Acetyl-CoA (liver)
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Cytosolic acetyl-CoA carboxylase 1 (ACACA) catalyzes the reaction of bicarbonate, ATP, and acetyl-CoA to form malonyl-CoA, ADP, and orthophosphate. The reaction is positively regulated by citrate. The human ACACA cDNA has been cloned (Abu-Elheiga et al. 1995) and the biochemical properties of the human enzyme have recently been described (Cheng et al. 2007; Locke et al. 2008). Four ACACA isoforms generated by alternative splicing have been identified as mRNAs - the protein product of the first has been characterized experimentally. ACACA uses biotin (Btn) and two Mn2+ ions per subunit as cofactors and its activity is increased by polymerization (Kim et al. 2010, Ingaramo & Beckett 2012). Cytosolic ACACA is thought to maintain regulation of fatty acid synthesis in all tissues but especially lipogenic tissues such as adipose tissue and lactating mammary glands.

Mid1-interacting protein 1 (MID1IP1, aka MIG12, SPOT14R, S14R) plays a role in the regulation of lipogenesis in the liver. It is rapidly upregulated by processes that induce lipogenesis (enhanced glucose metabolism, thyroid hormone administration) (Tsatsos et al. 2008). MID1IP1 forms a heterodimer with thyroid hormone-inducible hepatic protein (THRSP, aka SPOT14, S14), proposed to play the same role in lipogenesis as MID1IP1 (Aipoalani et al. 2010). This complex can polymerizes in fatty acid (FA) synthesis. Polymerization enhances ACACA and ACACB enzyme activities (Kim et al. 2010).

Literature References
PubMed ID Title Journal Year
16854592 Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes

Feder, JN, Chu, CH, Locke, GA, An, Y, Cheng, D, Tamura, JK, Wu, Y, Mintier, GA, Chen, L, Cook, JW, Harpel, MR

Protein Expr Purif 2007
7732023 Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms

Jayakumar, A, Wakil, SJ, Chirala, SS, Baldini, A, Abu-Elheiga, L

Proc Natl Acad Sci U S A 1995
18455495 Differential activation of recombinant human acetyl-CoA carboxylases 1 and 2 by citrate

Haque, T, Carney, RF, Locke, GA, Rendina, AR, Cheng, D, Tamura, JK, Marcinkeviciene, J, Witmer, MR

Arch Biochem Biophys 2008
Catalyst Activity

acetyl-CoA carboxylase activity of Btn-ACACA [cytosol]

This event is regulated
Positively by
Orthologous Events
Cross References
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