ALAS-1 is a nuclear-encoded mitochondrial matrix enzyme which catalyzes the condensation of glycine with succinyl-CoA to form delta-amino levulinate, CO2 and CoA. It regulates the first and rate-limiting step of heme biosynthetic pathway. It is one of the two isoforms of ALAS and is a pyridoxal-5 and quote; phosphate dependant housekeeping enzyme. It is ubiquitously expressed and is responsible of providing heme for cytochromes and other hemoproteins. ALAS1 in liver undergoes negative feedback regulation by heme. Transcription of ALAS1 gene is stimulated by cAMP and respiratory uncoupling whereas Phorbol esters and insulin repress ALAS1 gene expression. ALAS1 is suggested to be involved in reciprocal regulation of Heme biosynthesis and circadian clock suggesting a potential target for treatment of circadian disorders. ALAS1 gene expression is down regulated in Acute Liver failure resulting in altered heme metabolism and liver function.
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