3-Hydroxy-3-methylglutaryldithio-coenzyme A: a potent inhibitor of Pseudomonas mevalonii HMG-CoA reductase.
3-Hydroxy-3-methyl-1-thionoglutaryl-coenzyme A, a dithioester analog of 3-hydroxy-3-methylglutaryl-CoA, has been enzymatically synthesized using the HMG-CoA synthase catalyzed condensation of acetyl-CoA with 3-oxo-1-thionobutyryl-CoA. HMGdithio-CoA is a potent inhibitor of Pseudomonas mevalonii HMG-CoA reductase. Inhibition was mainly competitive with respect to HMG-CoA with a Kis of 0.086 +/- .01 microM and noncompetitive with respect to NADH with a Kis of 3.7 +/- 1.5 microM and a Kii of 0.65 +/- .05 microM in the presence of 110 microM (R.S)-HMG-CoA.
Wrensford
L V
LV
Department of Chemistry, Brown University, Providence, Rhode Island 02912.
Rodwell
V W
VW
Anderson
V E
VE
D000214:Acyl Coenzyme A / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D002645:Chickens; D002848:Chromatography, DEAE-Cellulose; D002852:Chromatography, Ion Exchange; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000302:isolation & purification / Q000378:metabolism; D007202:Indicators and Reagents; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D011485:Protein Binding; D011549:Pseudomonas / Q000201:enzymology*; D014462:Ultrafiltration
D000214:Acyl Coenzyme A; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007202:Indicators and Reagents; C070602:3-hydroxy-3-methylglutaryldithio-coenzyme A; D006904:Hydroxymethylglutaryl-CoA Synthase