MODULATION OF HMG-COA REDUCTASE-ACTIVITY BY PANTETHEINE PANTETHINE

The ability of pantetheine/pantethine to modulate the aptivity of HMG-CoA reductase (EC 1.1.1.3) was determined in vitro with rat liver microsomes. The decay of the activity was obtained with pantethine in the 10(ex-5)-10(ex-4) M range, whereas stimulation by panlgtheine occurred at 10(ex-3)-10(ex-2) M, as previously reported for GSSG and GSH, respectively. Inhibition of HMG-CoA by pantethine in isolated liver cells was also investigated by measuring the enzyme activity in microsomes isolated from hepatocytes incubated without or with 1 mM pantethine under conditions previously shown by us to induce inhibition of cholesterol synthesis from acetate. The enzyme amount was not modified by pantethine, but in cells treated with the disulphide, the relative amounts of the thiolic active forms of the enzyme, both phosphorylated and dephosphorylated, were decreased to about half compared to controls.