5-aminolevulinate synthase 1 (ALAS1)

5-aminolevulinate synthase 1 (ALAS1) is a PLP-dependent mitochondrial enzyme that catalyzes the condensation of glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), as the first and rate-limiting step in the heme biosynthesis pathway[1][3][4][5][6]. ALAS1 is ubiquitously expressed across tissues (housekeeping isozyme), whereas ALAS2 is erythroid-specific. Heme acts as a feedback regulator of ALAS1 activity through multiple mechanisms, including inhibition of transcription, translation, and protein transport/degradation[2]. Mutations in ALAS1 are associated with diseases such as X-linked sideroblastic anemia and can result in embryonic lethality if the gene is knocked out[1][4]. ALAS1 activity is essential for the synthesis of hemoproteins and overall cellular metabolism in mammals.

Other names

Delta-aminolevulinate synthase 1Aminolevulinic acid synthase 15-ALA synthase 1

Inhibition or regulation of enzyme activity influences heme biosynthesis; heme acts as a feedback inhibitor of ALAS1 at multiple levels, including mRNA synthesis, translation, and protein degradation[2].