AGPAT

AGPAT, or acylglycerol-3-phosphate acyltransferase, refers to a family of enzymes that catalyze the acylation of lysophosphatidic acid (LPA) to form phosphatidic acid (PA) in glycerolipid biosynthesis. These membrane-bound enzymes are primarily localized to the endoplasmic reticulum and, in some cases, other intracellular membranes. In humans, the AGPAT family comprises six known isoforms encoded by AGPAT1 through AGPAT6 genes, also referred to as LPAAT1–LPAAT6. The enzymes share conserved acyltransferase domains and typically contain multiple transmembrane segments that anchor them in membranes.

Biochemical activity involves converting LPA and an acyl-CoA donor into PA and CoA. Isoforms display varying substrate preferences for acyl-CoA species and LPA isomers, contributing to tissue-specific lipid composition and metabolic regulation.

Biological role centers on PA as a central intermediate in glycerolipid metabolism. By producing PA, AGPAT enzymes influence the synthesis of phospholipids and triglycerides, impacting membrane biogenesis, lipid storage, and adipocyte differentiation. Through regulation of lipid pools, AGPAT activity helps shape cellular lipid homeostasis and membrane properties in multiple tissues.

Clinical significance is highlighted by mutations in AGPAT2, which cause congenital generalized lipodystrophy type 1, a disorder characterized by loss of adipose tissue and metabolic complications. Other AGPAT family members have been investigated for associations with lipid traits and metabolic phenotypes, and animal models with disrupted AGPAT genes show altered adiposity and glycerolipid metabolism.

See also: lysophosphatidic acid acyltransferase; glycerolipid metabolism; lipodystrophy.