HLCS biotinylates 6xMCCC1:6xMCCC2

Biotin (Btn) acts as a coenzyme to 4 carboxylases which exist in their inactive apo forms. In the cytosol, these apo carboxylases are biotinylated to their active halo forms by the activity of biotin-protein ligase (HCLS) (Ingaramo & Beckett 2012, Hiratsuka et al. 1998, Bailey et al. 2010). HCLS is localised to the cytosol and mitochondrion so can perform this activity in either of these locations. Defects in HLCS causes holocarboxylase synthetase deficiency (HLCS deficiency aka biotin-responsive multiple carboxylase deficiency; MIM:253270). HLCS deficiency is an autosomal recessive disorder whereby deficient HLCS activity results in reduced activity of multiple carboxylases. Symptoms include metabolic acidosis, organic aciduria, lethargy, hypotonia, convulsions and dermatitis (Suzuki et al. 2005). Methylcrotonoyl-CoA carboxylase is most likely functional as a dodecamer, composed of 6 Btn-containing alpha subunits (MCCC1) and six beta subunits (MCCC2). The exact order in which this complex is constructed is unknown.

生物素（Btn）作为一种辅酶，与存在于其非活性前体形式中的4种羧化酶相互作用。在细胞质中，这些前体羧化酶通过生物素-蛋白连接酶（HCLS）的活性被生物素化，转变为活性卤素形式（Ingaramo & Beckett 2012，Hiratsuka 等人 1998，Bailey 等人 2010）。HCLS定位于细胞质和线粒体，因此能够在这些位置的任一位置执行此活性。HCLS缺陷会导致全羧化酶合成酶缺乏症（HLCS缺乏症，又称生物素响应性多羧化酶缺乏症；MIM:253270）。HLCS缺乏症是一种常染色体隐性遗传性疾病，其中HCLS活性不足导致多种羧化酶活性降低。症状包括代谢性酸中毒、有机酸尿、嗜睡、肌张力低下、惊厥和皮炎（Suzuki 等人 2005）。甲基丙二酰辅酶A羧化酶很可能作为十二聚体发挥作用，由6个含有生物素（Btn）的α亚基（MCCC1）和6个β亚基（MCCC2）组成。构建此复合体的确切顺序尚不清楚。