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

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

Stable Identifier

R-HSA-8876889

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, mitochondrial outer membrane

Synonyms

acetyl-CoA + ATP + hydrogencarbonate => ADP + H(+) + malonyl-CoA + phosphate

ReviewStatus

5/5

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

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Mitochondrial acetyl-CoA carboxylase 2 (ACACB, ACC2) (Kim et al. 2007) catalyses the reaction of bicarbonate, ATP, and acetyl-CoA to form malonyl-CoA, ADP, and orthophosphate. The reaction is positively regulated by citrate. ACACB 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). ACACB is located on the outer mitochondrial membrane and is involved in the regulation of mitochondrial fatty acid oxidation through the inhibition of carnitine palmitoyltransferase 1 by its product malonyl-CoA (Abu-Elheiga et al. 2000).

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 polymerize acetyl-CoA carboxylases 1 and 2 (ACACA and B), the first committed enzymes in fatty acid (FA) synthesis. Polymerization enhances ACACA and ACACB enzyme activities (Kim et al. 2010).

Literature References

PubMed ID	Title	Journal	Year
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
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
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
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
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
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
22123817	Selectivity in post-translational biotin addition to five human carboxylases Ingaramo, M, Beckett, D	J. Biol. Chem.	2012