Cytosolic Cofactors and Dihydrolipoamide Stimulate Hepatic Microsomal 5′-Deiodination*

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Abstract
The effect of rat hepatic cytosolic constituents on microsomal 5''-deiodinase (5''-DI) activity in the presence of the dihydrolipoamide-generating system or dihydrolipoamide itself has been studied. Reconstitution experiments have demonstrated for the 1st time the essential role of cytosol as well as lipoamide and NADH in the activation of 5''-iodothyronine DI to a level equivalent to that attained in the presence of 5 mM dithiothreitol. Omission of NADH, lipoamide or cytosol reduced the DI activity to 86%. By gel filtration chromatography of the cytosol, a fraction of intermediate MW (.apprx. 13,000) was highly stimulatory of microsomal DI in washed microsomes, provided either a dihydrolipoamide-generating system (lipoamide dehydrogenase, as well as NADH and lipoamide) or dihydrolipoamide alone was added. A possible role is suggested for a heretofore unreported reducing system influencing hepatic 5''-deiodination, wherein cytosolic cofactors appear to function as efficient intermediaries which enhance the action of a dihydrolipoamide in the activation of isolated hepatic microsomal 5''-DI.