Glucose-6-phosphate dehydrogenase from Neisseria gonorrhoeae: partical characterization of the enzyme and inhibition by long-chain fatty acid acyl-coenzyme A derivatives.
The glucose-6-phosphate dehydrogenase from Neisseria gonorrhoeae was inhibited by long-chain fatty acid acyl-coenzyme A derivatives. The inhibition was increased at low concentrations of flucose 6-phosphate and was greater with the NAD-linked activity (ca. 0.05 mM inhibitor required for 50% inhibition) than with the NADP-linked activity (ca. 0.2 mM required for 50% inhibition). Bovine serum albumin and spermine could prevent the inhibition by the acyl coenzyme A derivatives, but neither of these compounds nor high concentrations of cofactors or substrate could reverse the effect. Dilution of enzyme-inhibitor preincubation mixtures appeared to reverse the inhibition. The inhibition by steroyl-coenzyme A was of the mixed type, and the inhibitor appeared to have a greater affinity for the free enzyme (Ki = 0.016-0.05 mM) than for enzyme bound to cofactor or substrate (Kis = 0.07-0.08 mM). Glucose-6-phosphate dehydrogenase activity was also inhibited competitively by adenosine 5'-triphosphate and was strongly regulated by adenylate energy charges values between 0.9 and 1.0. Kinetic and other characteristics of the enzyme are presented, and the possible role of glucose-6-phosphate dehydrogenase as a target for fatty acid toxicity in gonococci, mediated in the form of the acyl-coenzyme A derivatives, is discussed.
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008970:Molecular Weight; D009243:NAD / Q000494:pharmacology; D009344:Neisseria gonorrhoeae / Q000201:enzymology*; D009829:Oleic Acids / Q000494:pharmacology; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D013229:Stearic Acids / Q000494:pharmacology
D000214:Acyl Coenzyme A; D009829:Oleic Acids; D013229:Stearic Acids; D009243:NAD; C017585:oleoyl-coenzyme A; D010171:Palmitoyl Coenzyme A; C017725:stearoyl-coenzyme A; D000255:Adenosine Triphosphate; D005954:Glucosephosphate Dehydrogenase