INHIBITORS OF CATALYTIC ACTIVITY OF BOVINE ADRENAL GLUCOSE-6-PHOSPHATE DEHYDROGENASE

Purified cow adrenal glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADP+ oxidoreductase, EC 1.1.1.49) was examined for its reactivity with compounds that reduce its catalytic activity. Varying degrees of inhibition were observed with many steroids such as estrogens, androgens, progesterones, with long chain fatty acids and with thyronine compounds. Lineweaver-Burk plots of individual inhibitor experiments showed that estriol competes with NADP+ and glucose 6-phosphate. 11β-Hydroxyprogesterone and tetraiodothyronine compete with NADP+ but not with glucose 6-phosphate; 16α-hydroxyandrostenedione showed uncompetitive kinetics with both the nucleotide and substrate. Palmitic acid was noncompetitive with the nucleotide and substrate. Double inhibitor experiments indicated that estriol, 11β-hydroxyprogesterone, 16α-hydroxyandrostenedione and tetraiodothyronine bind to the same site(s) in the enzyme. The binding site(s) for palmitic acid is probably separate. Possible models are discussed. © 1969.