ALAS condenses SUCC-CoA and Gly to form dALA

The committed step for porphyrin synthesis is the formation of 5-aminolevulinate (ALA) by condensation of glycine (from the general amino acid pool) and succinyl-CoA (from the TCA cycle), in the mitochondrial matrix. The reaction is catalyzed by two different ALA synthases, one expressed ubiquitously (ALAS1) and the other only expressed in erythroid precursors (ALAS2). Both enzymes are expressed as homodimers and require pyridoxal 5-phosphate as a cofactor.<br>No disease-causing mutations of ALAS1 have been recognised in humans. Mutations in ALAS2 cause X-linked sideroblastic anaemia (XLSA), characterised by a microcytic hypochromic anaemia.

在卟啉合成的关键步骤中，通过甘氨酸（来源于通用氨基酸库）与琥珀酰辅酶A（来源于三羧酸循环）的缩合反应，在细胞线粒体基质中形成5-氨基卟啉酸（ALA）。此反应由两种不同的ALA合酶催化，其中一种在全身表达（ALAS1），另一种仅在红细胞前体细胞中表达（ALAS2）。两种酶均以同源二聚体的形式表达，并需要吡哆醛-5'-磷酸作为辅因子。在人类中，尚未识别出导致疾病产生的ALAS1突变。ALAS2的突变会导致X连锁的无效红细胞贫血（XLSA），其特征为小细胞性低色素性贫血。