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

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

Stable Identifier

R-HSA-75851

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

Formation of Malonyl-CoA from Acetyl-CoA

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Btn-ACACA:2Mn2+ polymer carboxylates Ac-CoA to form Mal-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 polymerisation (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 polymerise acetyl-CoA carboxylases 1 and 2 (ACACA and B), the first committed enzymes in fatty acid (FA) synthesis. Polymerisation 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