Selenium inhibition of avian fatty acid synthetase complex

Injection of 0.48 or 0.72 mg of selenium/100 g body weight (as Na2SeO3) into 3-week-old chicks depressed hepatic activity of fatty acid synthetase compared with saline-injected controls. In in vitro experiments with fatty acid synthetase purified to homogeneity, Na2SeO3 was a competitive inhibitor (Ki = ca. 70 micronM). Dithiothreitol (DTT) at low concentrations increased the inhibition of the enzyme by Na2SeO3. At higher DTT concentrations the potentiating effect of DTT on selenium inhibition of the enzyme disappeared. At still higher DTT concentrations, selenium inhibition of fatty acid synthetase was partically relieved. If DTT and Na2SeO3 (2 : 1 molar ratio, respectively) in inhibitory concentrations, were reacted together prior to addition to enzyme and substrate, no inhibition was observed. Potentiation of selenium inhibition of fatty acid synthetase was observed with 2-mercaptoethanol but not with ascorbate. Several organic seleno-compounds were not inhibitory. The data suggest that selenium inhibits fatty acid synthetase by reversible bonding to the sulfhydryl (SH) groups (possibly at the active sites for acetyl-CoA and/or malonyl-CoA binding) of the enzyme. Selenotrisulfide formation involving selenium and the SH groups from the enzyme and thiol compounds is advanced as a possible explanation for the interaction among Se, DTT and enzyme observed in these experiments.