A novel pathway for lipid biosynthesis: the direct acylation of glycerol.
The acylation of glycerol-3-phosphate by acyl-CoA is regarded as the first committed step for the synthesis of the lipoidal moiety in glycerolipids. The direct acylation of glycerol in mammalian tissues has not been demonstrated. In this study, lipid biosynthesis in myoblasts and hepatocytes was reassessed by conducting pulse-chase experiments with [1,3-(3)H]glycerol. The results demonstrated that a portion of labeled glycerol was directly acylated to form monoacylglycerol and, subsequently, diacylglycerol and triacylglycerol. The direct acylation of glycerol became more prominent when the glycerol-3-phosphate pathway was attenuated or when exogenous glycerol levels became elevated. Glycerol:acyl-CoA acyltransferase activity, which is responsible for the direct acylation of glycerol, was detected in the microsomal fraction of heart, liver, kidney, skeletal muscle, and brain tissues. The enzyme from pig heart microsomes displayed optimal activity at pH 6.0 and the preference for arachidonyl-CoA as the acyl donor. The apparent K(m) values for glycerol and arachidonyl-CoA were 1.1 mM and 0.17 mM, respectively. The present study demonstrates the existence of a novel lipid biosynthetic pathway that may be important during hyperglycerolemia produced in diabetes or other pathological conditions.
Lee
D P
DP
Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, 770 Bannatyne Ave., Winnipeg, Manitoba, Canada R3E 0W3.
Deonarine
A S
AS
Kienetz
M
M
Zhu
Q
Q
Skrzypczak
M
M
Chan
M
M
Choy
P C
PC
D000214:Acyl Coenzyme A / Q000378:metabolism; D000215:Acylation / Q000187:drug effects; D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005989:Glycerides / Q000096:biosynthesis; D005990:Glycerol / Q000378:metabolism* / Q000494:pharmacology; D005991:Glycerol Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005994:Glycerophosphates / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis*; D051381:Rats; D015398:Signal Transduction; D013552:Swine
D000214:Acyl Coenzyme A; D005989:Glycerides; D005994:Glycerophosphates; D008055:Lipids; C026563:arachidonyl-coenzyme A; C029620:alpha-glycerophosphoric acid; D000217:Acyltransferases; D005991:Glycerol Kinase; D005990:Glycerol