Regulation of acetyl-CoA carboxylase by ADP-ribosylation.
Because of certain similarities between acetyl-CoA carboxylase (ACC) and tubulin, and the recent demonstration of the ADP-ribosylation of tubulin by cholera toxin, we have investigated a potential role for ADP-ribosylation in the regulation of ACC activity. Incubation of purified rat liver ACC with cholera toxin in the presence of millimolar concentrations of [adenylate-32P]NAD results in a time-dependent incorporation of ADP-ribose into ACC of greater than 2 mol/mol of enzyme subunit, accompanied by a marked inactivation of enzyme activity. This effect is not mimicked by pertussis toxin, ADP-ribose, or ribose 5-phosphate. Incubation of labeled ACC with snake venom phosphodiesterase and alkaline hydrolysis release 32P-products tentatively identified by high-performance liquid chromatography as 5'-[32P]AMP and [32P]ADP-ribose, respectively. These data are consistent with a mono-ADP-ribosylation of ACC catalyzed by cholera toxin. Phosphodiesterase treatment of inactivated ACC partially restores enzyme activity. The effects of ADP-ribosylation of ACC are expressed both as a decrease in the enzyme Vmax and as an increase in the apparent Ka for citrate. These results suggest that ACC might be a substrate for endogenous ADP-ribosyltransferases and that this covalent modification could be an important regulatory mechanism for the modulation of fatty acid synthesis in vivo.
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D007700:Kinetics; D008025:Ligases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D010761:Phosphorus Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D012267:Ribosemonophosphates / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D010761:Phosphorus Radioisotopes; D012267:Ribosemonophosphates; D014404:Tubulin; D000246:Adenosine Diphosphate Ribose; C031626:ribose-5-phosphate; D002772:Cholera Toxin; D008025:Ligases; D000103:Acetyl-CoA Carboxylase