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).
Ingaramo, M, Beckett, D
Abu-Elheiga, L, Almarza-Ortega, DB, Baldini, A, Wakil, SJ
Kim, CW, Moon, YA, Park, SW, Cheng, D, Kwon, HJ, Horton, JD
Aipoalani, DL, O'Callaghan, BL, Mashek, DG, Mariash, CN, Towle, HC
Park, S, Hwang, IW, Makishima, Y, Perales-Clemente, E, Kato, T, Niederländer, NJ, Park, EY, Terzic, A
Brinkley, WR, Zhong, L, Woldegiorgis, G, Wakil, SJ
Tsatsos, NG, Augustin, LB, Anderson, GW, Towle, HC, Mariash, CN
Kim, KW, Yamane, H, Zondlo, J, Busby, J, Wang, M
acetyl-CoA carboxylase activity of Btn-ACACA:2Mn2+ polymer [cytosol]
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).
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