THE POLYMERIZATION OF ACETYL-COA CARBOXYLASE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 258  (21) , 3051-3055
Abstract
Citrate, an allosteric activator of [chicken liver] acetyl-CoA carboxylase, induces polymerization of an inactive protomeric form of the enzyme into an active filamentous form composed of 10-20 protomers. The light-scattering properties of the carboxylase were used to study the kinetics of its polymerization and depolymerization. Stopped flow kinetic studies established that polymerization is a 2nd order process, with a second order rate constant of 597,000 M-1 s-1. There appears to be 2 steps which limit polymerization of the inactive carboxylase protomer: a rapid citrate-induced conformational change which is independent of enzyme concentration and leads to an active protomeric form of the enzyme and the dimerization of the active protomer, which constitutes the 1st step of polymerization and is enzyme concentration-dependent. Dimerization is the rate-limiting step of acetyl-CoA carboxylase polymerization. Depolymerization of fully polymerized acetyl-CoA carboxylase is caused by malonyl-CoA, ATP .cntdot. Mg and Mg2+. Both malonyl-CoA and ATP .cntdot. Mg (and HCO3-) compete with citrate in the maintenance of a given state of the promoter-polymer equilibrium apparently by carboxylating the enzyme to form enzyme-biotin-CO2- which destabilizes the polymeric form. Free citrate is the species responsible for polymerizing the enzyme and Mg2+ causes depolymerization of the enzyme by lowering the concentration of free citrate.