Mercury inhibition of avian fatty acid synthetase complex

Abstract

( 1) Subcutaneous or intra-abdominal injections of 8 mg of HgCl 2/100 g body weight markedly depressed hepatic fatty acid synthetase activity of chicks at l h postinjection. The depression occurred despite the fact that the chicks continued to eat up until the time they were killed. Under these same conditions, the hepatic activity of acetyl-CoA car☐ylase (EC 6.4.1.2) was not affected by HgCl 2, while the activity of the mitochondrial system of fatty acid elongation was stimulated. ( 2) When 2-mercaptoethanol was included in the incubation medium for a highly purified preparation of fatty acid synthetase, 500 μ M HgCl 2 was required to show definite inhibition of the enzyme. When 2-mercaptoethanol was omitted, 50 μ M HgCl 2 was inhibitory and 100 μ M HgCl 2 abolished enzyme activity. ( 3) 2 m M dithiothreitol completely protected the purified fatty acid synthetase preparation from inhibition by 100 μ M HgCl 2. When dithiothreitol was added after the addition of enzyme to the mercury-containing medium, protection of the enzyme was not complete. ( 4) Dialysis of cytosol fractions from chicks injected with HgCl 2 against 500 vol. of 0.2 M potassium phosphate buffer (pH 7.0) containing 1 m M EDTA and 10 m M dithiothreitol for 4 h at 4° stimulated the fatty acid synthetase activity of the fractions. Dialysis of cytosol fractions from noninjected chicks under the same conditions was without effect on fatty acid synthetase activity. ( 5) These data support the nypothesis that the inhibitory effect of HgCl 2 administered in vivo on hepatic fatty acid synthetase activity in chicks is mediated through the interaction of mercury with the sulfhydryl groups of the enzyme.