SUCLG1/G2 cleaves succinyl-CoA

Mitochondrial succinate CoA ligase (GDP-forming) catalyzes the reversible conversion of succinyl CoA to succinate plus Coenzyme A, coupled to the conversion of GDP and orthophosphate to GTP. The enzyme is a heterodimer containing SUCLG1 and SUCLG2 monomers.<p>The enzyme catalyzing the reaction in vertebrates is a heterodimer that occurs in two isoforms. The enzymes have been purified from pigeon and rat tissue and characterized in detail. Both isoforms, an alpha:betaA heterodimer and an alpha:betaG heterodimer, catalyze the reversible conversion of succinyl CoA to succinate plus Coenzyme A. The alpha:betaA heterodimer couples this conversion to the synthesis of ATP from ADP and orthophosphate, while the alpha:betaG heterodimer couples it to the synthesis of GTP from GDP and orthophosphate (Johnson et al. 1998a,b; Lambeth et al. 2004). Consistent with these results in model systems, patients homozygous for a mutant allele of the gene encoding the ADP enzyme beta subunit, SUCLA2, are deficient in succinyl CoA ligase activity (Elpeleg et al. 2005).<p>Both isoforms are found in vivo, and appear to be expressed at different levels in various tissues. Their relative contributions to the flux of carbon atoms through the TCA cycle are unknown. Genetic and biochemical data suggest that the alpha:betaA isoform may be required to catalyze the reverse reaction, conversion of succinate, Coenzyme A, and ATP to succinyl CoA, ADP, and orthophosphate for heme biosynthesis (Furuyama and Sassa 2000).<p>Mutations in SUCLG1 are the cause of the infantile metabolic disease named mitochondrial DNA depletion syndrome 9 (MTDPS9; MIM:245400; reviewed by Molaei Ramsheh et al., 2020).

线粒体琥珀酰辅酶A合酶（GDP形成型）催化琥珀酰辅酶A可逆转化为琥珀酸及辅酶A，此过程与鸟苷二磷酸（GDP）及正磷酸盐转化为鸟苷三磷酸（GTP）相偶联。该酶为异源二聚体，由SUCLG1和SUCLG2单体组成。<p>催化脊椎动物中该反应的酶亦为异源二聚体，存在两种同工酶形式。该酶已从鸽和鼠组织中纯化并进行了详细表征。两种同工酶，即α:βA异源二聚体和α:βG异源二聚体，均催化琥珀酰辅酶A的可逆转化为琥珀酸及辅酶A。α:βA异源二聚体将此转化与ADP和正磷酸盐合成ATP的过程相偶联，而α:βG异源二聚体则与GDP和正磷酸盐合成GTP的过程相偶联（Johnson等，1998a,b；Lambeth等，2004）。与模型系统中的这些结果一致，对于编码ADP酶β亚基的基因SUCLA2的突变纯合子患者，琥珀酰辅酶A合酶活性存在缺陷（Elpeleg等，2005）。<p>两种同工酶均存在于体内，并在不同组织中表现出不同的表达水平。它们对三羧酸循环中碳原子流量的相对贡献尚不清楚。遗传学和生化数据表明，α:βA同工酶可能催化逆向反应，即将琥珀酸、辅酶A和ATP转化为琥珀酰辅酶A、ADP和正磷酸盐，以供血红素生物合成（Furuyama和Sassa，2000）。<p>SUCLG1基因突变是婴儿代谢性疾病线粒体DNA耗竭综合征9（MTDPS9；MIM：245400；由Molaei Ramsheh等，2020年综述）的病因。