Rat Aminolevulinate Delta Synthase 1 (ALAS1) Protein

Background

5-Aminolevulinate Synthase 1 (ALAS1) is the ubiquitously expressed, non-specific isoform of the enzyme catalyzing the first and rate-limiting step of heme biosynthesis. ALAS1 converts glycine and succinyl-CoA into 5-aminolevulinic acid (ALA) within mitochondria, a critical precursor in the heme production pathway. Its expression and activity are tightly regulated by intracellular heme levels, reflecting its central role in maintaining heme homeostasis. ALAS1 is induced in response to increased demand for cytochromes in liver cells, particularly during drug metabolism and detoxification processes mediated by cytochrome P450 enzymes. Dysregulation of ALAS1 can lead to disorders such as acute intermittent porphyria (AIP), characterized by the accumulation of toxic heme precursors, resulting in neurovisceral symptoms. Therapeutic modulation of ALAS1 activity, including heme supplementation or small-molecule inhibitors, is a key strategy in managing porphyric crises and related metabolic dysfunctions.