5-aminolevulinate synthase

5-Aminolevulinate synthase (ALAS) is an enzyme that catalyzes the first step in the heme biosynthesis pathway. It is a pyridoxal phosphate (PLP)-dependent enzyme that condenses glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA). There are two forms of ALAS in the human body: ALAS1, which is expressed in all tissues, and ALAS2, which is expressed only in the erythroid lineage.

Function

The primary function of 5-aminolevulinate synthase is to catalyze the production of 5-aminolevulinic acid, the first compound in the heme biosynthesis pathway. Heme is an essential component of various proteins, including hemoglobin, myoglobin, and cytochromes. Therefore, ALAS plays a crucial role in the function of these proteins.

Structure

5-Aminolevulinate synthase is a homodimer, with each monomer consisting of a large domain and a small domain. The large domain contains the active site, which is where the reaction takes place. The small domain is involved in substrate binding.

Clinical significance

Mutations in the genes encoding 5-aminolevulinate synthase can lead to various disorders. For example, mutations in the ALAS2 gene can cause X-linked sideroblastic anemia, a condition characterized by an inability to produce sufficient amounts of heme. Similarly, mutations in the ALAS1 gene can lead to ALA dehydratase deficiency porphyria, a rare metabolic disorder.

See also

• Heme
• Enzyme
• Glycine
• Succinyl-CoA
• 5-Aminolevulinic acid
• X-linked sideroblastic anemia
• ALA dehydratase deficiency porphyria