Btn-ACACA:2Mn2+ polymer carboxylates Ac-CoA to form Mal-CoA

Stable Identifier
Reaction [transition]
Homo sapiens
Formation of Malonyl-CoA from Acetyl-CoA
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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
9099716 Human acetyl-CoA carboxylase 2. Molecular cloning, characterization, chromosomal mapping, and evidence for two isoforms.

Wakil, SJ, Baldini, A, Abu-Elheiga, L, Almarza-Ortega, DB

J Biol Chem 1997
22123817 Selectivity in post-translational biotin addition to five human carboxylases

Ingaramo, M, Beckett, D

J. Biol. Chem. 2012
20457939 Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 provides a tertiary level of regulation of fatty acid synthesis

Kim, CW, Cheng, D, Horton, JD, Kwon, HJ, Park, SW, Moon, YA

Proc. Natl. Acad. Sci. U.S.A. 2010
20233797 Overlapping roles of the glucose-responsive genes, S14 and S14R, in hepatic lipogenesis

Mariash, CN, Mashek, DG, Aipoalani, DL, Towle, HC, O'Callaghan, BL

Endocrinology 2010
24277613 Spot14/Mig12 heterocomplex sequesters polymerization and restrains catalytic function of human acetyl-CoA carboxylase 2

Hwang, IW, Makishima, Y, Niederländer, NJ, Terzic, A, Kato, T, Perales-Clemente, E, Park, S, Park, EY

J. Mol. Recognit. 2013
10677481 The subcellular localization of acetyl-CoA carboxylase 2

Wakil, SJ, Brinkley, WR, Woldegiorgis, G, Zhong, L

Proc Natl Acad Sci U S A 2000
18556348 Hepatic expression of the SPOT 14 (S14) paralog S14-related (Mid1 interacting protein) is regulated by dietary carbohydrate

Mariash, CN, Towle, HC, Anderson, GW, Augustin, LB, Tsatsos, NG

Endocrinology 2008
17223360 Expression, purification, and characterization of human acetyl-CoA carboxylase 2

Wang, M, Zondlo, J, Yamane, H, Busby, J, Kim, KW

Protein Expr Purif 2007
Catalyst Activity

acetyl-CoA carboxylase activity of Btn-ACACA:2Mn2+ polymer [cytosol]

This event is regulated
Positively by
Orthologous Events
Cross References
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