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Hepatic monoacylglycerol acyltransferase is regulated by sn-1,2-diacylglycerol and by specific lipids in Triton X-100/phospholipid-mixed micelles.

Authors
  • Bhat, B G
  • Wang, P
  • Coleman, R A
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry & Molecular Biology (ASBMB)
Publication Date
May 06, 1994
Volume
269
Issue
18
Pages
13172–13178
Identifiers
PMID: 8175745
Source
Medline
License
Unknown

Abstract

The lipid cofactor requirement of hepatic monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22) was studied in Triton X-100/lipid-mixed micelles. Anionic phospholipids and anionic lysophospholipids stimulated MGAT activity, whereas fatty acids and sphingosine inhibited enzyme activity. Phosphatidic acid was a potent activator, stimulating MGAT 11-fold at 4.2 mol %. Kinetic studies revealed that phosphatidic acid, with an apparent Ka of 0.26 mol %, was a better activator than phosphatidylserine, phosphatidylinositol, or cardiolipin. Of the anionic lysophospholipids, lysophosphatidic acid was a better activator than lysophosphatidylserine, stimulating maximally at less than 3 mol %. Oleate was a more potent inhibitor (Ki, 2.4 mol %) than sphingosine (Ki, 18.3 mol %). The dependence of MGAT on sn-2-monoacylglycerol was not cooperative in the absence or presence of anionic phospholipids, oleic acid, or sphingosine. The apparent Km for sn-2-monoC18:1-glycerol was 1.24 mol % in the presence of maximally activating phospholipid and 0.19 mol % when phospholipid was omitted. MGAT's product sn-1,2-diacylglycerol was a weaker activator than the anionic phospholipids, but the effects of diacylglycerol and phospholipid were additive. Activation by sn-1,2-diC18:1-glycerol was highly cooperative with a Hill coefficient of 3.6. Activation was specific for the sn-1,2-stereoisomer; neither 1,3-diacylglycerol nor the ether analogs of sn-1,2- or 1,3-diacylglycerol were activators. Since several of the lipid modulators of MGAT activity are intracellular second messengers, these data suggest the possibility that regulatory links exist between signal transduction and the synthesis of complex lipids via the monoacylglycerol pathway.

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