Inhibitory effects of sulfhydryl reagents on acetyl-CoA carboxylase from rat mammary gland.
Rat mammary gland acetyl-CoA carboxylase (acetyl-CoA:carbon dioxide ligase (ADP forming), EC 6.4.1.2) is rapidly and irreversibly inactivated by micromolar concentrations of S-(4-bromo-2,3-dioxobutyl)-CoA (BDB-CoA) or p-hydroxymercuribenzoate (PHMB). Inhibition of both half reactions (i.e., the biotin carboxylation and the carboxyltransferase) catalyzed by acetyl-CoA carboxylase closely parallels loss in overall activity (malonyl-CoA synthesis). The presence of a substrate or product (acetyl-CoA, ATP, ADP, Pi) or inhibitor (palmitoyl-CoA) does not protect the enzyme from inhibition caused by BDB-CoA or PHMB. On the other hand, citrate, an activator of acetyl-CoA carboxylase, affords substantial protection against inhibition by BDB-CoA and PHMB. Covalent modification by BDB-CoA or PHMB appears to lock acetyl-CoA carboxylase in an inactive conformation (15-30 S) that is unable to undergo citrate-induced self-association into the catalytically competent polymeric form.
D000105:Acetyl Coenzyme A / Q000494:pharmacology; D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002499:Centrifugation, Density Gradient; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D003065:Coenzyme A / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006902:Hydroxymercuribenzoates / Q000494:pharmacology*; D007774:Lactation; D008025:Ligases / Q000037:antagonists & inhibitors*; D008321:Mammary Glands, Animal / Q000201:enzymology*; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats
D002951:Citrates; D006902:Hydroxymercuribenzoates; C030601:4-hydroxymercuribenzoate; D010171:Palmitoyl Coenzyme A; D019343:Citric Acid; C017091:4-bromo-2,3-dioxobutyl-coenzyme A; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate; D008025:Ligases; D000103:Acetyl-CoA Carboxylase; D003065:Coenzyme A