Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis

Abstract

Triacylglycerol (TAG) synthesis and storage in tissues such as adipose tissue and liver have important roles in metabolic homeostasis. The molecular identification of genes encoding enzymes that catalyze steps in TAG biosynthesis from glycerol 3-phosphate has revealed an unexpected number of protein isoforms of the glycerol phosphate acyltransferase (GPAT), acylglycerolphosphate acyltransferase (AGPAT), and lipin (phosphatidate phosphatase) families that appear to catalyze similar biochemical reactions. However, on the basis of available data for a few members in which genetic deficiencies in mouse and/or human have been studied, we postulate that each GPAT, AGPAT, and lipin family member likely has a specialized role that may be uncovered through careful biochemical and physiological analyses.

Fig. 1.

Glycerol phosphate pathway for de novo triacylglycerol (TAG) and glycerophospholipid synthesis. GPAT, glycerol-3-phosphate acyltransferase; LPA, lysophosphatidic acid; AGPAT, 1-acylglycerol-3-phosphate acyltransferase; PI, phosphatidylinositol; PG, phosphatidylglycerol; CL, cardiolipin; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PS, phosphatidylserine; DAG, diacylglycerol; DGAT, diacylglycerol acyltransferase.

Fig. 2.

Domain structure of GPAT, AGPAT, and lipin proteins. Small bars above or below the peptide diagrams indicate the position of predicted transmembrane (TM) domains in GPAT and AGPAT proteins. N-LIP, amino-terminal lipin domain; C-LIP, carboxyl-terminal lipin domain; NLS, nuclear localization signal; PAP, phosphatidate phosphatase motif.