Meta-Biol

• Pathways

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).