Age-Dependent Sensitivity and Specific Isoenzyme Inhibition of Glucose-6-Phosphate Dehydrogenase by Dehydroepiandrosterone
Glucose-6-phosphate dehydrogenase (EC 220.127.116.11) is the rate-limiting enzyme in the hexosemonophosphate pathway and plays an important role in lipogenesis and steroid biosynthesis. The enzyme is inhibited by steroid hormones, as was first reported by Marks and Banks /1/ and by McKerns et al /2/. Levy /3/ found that dehydroepi-androsterone inhibited the NADP — but not the NAD — linked G-6-PDH isolated from mammary glands of lactating rats. Urea, glycerol, high pH and increased temperature were found to reverse the inhibition by dehydroepiandrosterone, suggesting alterations in the three-dimensional structure of the enzyme and the removal of the steroid- binding site from the proximity of the active centre. Human testicular /4/, ovarian /5/ an-d placental /6/ G-6-PDH are also inhibited by different steroid hormones as well as by their derivatives, analogues and conjugates, dehydroepiandrosterone (DHEA) being the most potent inhibitor in vitro. With rat liver G-6-PDH, Lopez and Rene /9/ have shown that at 5.10 -5 M dehydroepiandro sterone uniformly inhibits all four isoenzymes with complete disappearance of band D at the higher concentration of 10 -4 M.
KeywordsIsoenzyme Pattern Endogenous Steroid Hydrophobic Bond Heart Homogenate Inhibitory Steroid
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