Glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) (GPAM)

Glycerol-3-phosphate acyltransferase, mitochondrial (GPAM), also known as GPAT1, is a rate-limiting enzyme located on the outer mitochondrial membrane that catalyzes the initial step in the de novo synthesis of triglycerides and glycerophospholipids (UniProt Q9HCL3). By converting glycerol-3-phosphate and long-chain fatty acyl-CoAs into lysophosphatidic acid, GPAM plays a pivotal role in partitioning fatty acids toward storage as triacylglycerol rather than toward oxidation (PubMed: 21835944). Overexpression or increased activity of GPAM in the liver is strongly linked to the development of hepatic steatosis, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) (PubMed: 31413166). Consequently, GPAM mRNA has emerged as a therapeutic target, with antisense oligonucleotides (ASOs) like IONIS-GPAM-LRx designed to selectively reduce its expression (Ionis Pharmaceuticals). By lowering GPAM protein levels, these therapies aim to decrease hepatic lipid accumulation and improve metabolic profiles in patients with NASH or related metabolic disorders.

Other names

GPAT1GPATMitochondrial glycerol-3-phosphate acyltransferase 1Glycerol-3-phosphate acyltransferase 1

Antisense oligonucleotide-mediated degradation of GPAM mRNA to reduce protein expression and inhibit hepatic triglyceride synthesis (Ionis Pharmaceuticals).