Inhibition of glycerol-3-phosphate acyltransferase by analogs of glycerol-3-phosphate.
Analogs of glycerol-3-phosphate were tested as substrates or inhibitors of the glycerol-3-phosphate acyltransferases of mitochondria and microsomes. (rac)-3,4-Dihydroxybutyl-1-phosphonate, (rac)-glyceraldehyde 3-phosphate, (rac)-3-hydroxy-4-oxobutyl-1-phosphonate, (1S,3S)-1,3,4-trihydroxybutyl-1-phosphonate, and (1R,3S)-1,3,4 trihydroxybutyl-1-phosphonate were competitive inhibitors of both mitochondrial and microsomal sn-glycerol-3-phosphate acyltransferase activity. An isosteric analog of dihydroxyacetone phosphate, 4-hydroxy-3-oxobutyl-1-phosphonate, was a much stronger competitive inhibitor of the microsomal than the mitochondrial enzyme. Phenethyl alcohol was a noncompetitive inhibitor of both the microsomal and the mitochondrial acyltransferases. The product of the mitochondrial acyltransferase reaction with (rac)-3,4-dihydroxybutyl-1- phosphonate was almost exclusively (rac)-4-palmitoyloxy-3-hydroxybutyl-1-phosphonate. The microsomal acylation reaction generated both the monoacyl product and (S)-3,4-dipalmitoyloxybutyl-1-phosphonate. The apparent Km for (S)-3,4-dihydroxybutyl-1-phosphonate was 2.50 and 1.38 mM for the mitochondrial and microsomal enzymes, respectively.
Stein
T A
TA
Department of Surgery, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY 11042.
Engel
R R
RR
Tropp
B E
BE
D000215:Acylation; D000818:Animals; D002072:Butylene Glycols / Q000378:metabolism / Q000494:pharmacology; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005994:Glycerophosphates / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D063065:Organophosphonates; D051381:Rats
D002072:Butylene Glycols; D005994:Glycerophosphates; D063065:Organophosphonates; C013493:3,4-dihydroxybutyl-1-phosphonic acid; D005992:Glycerol-3-Phosphate O-Acyltransferase