Hydroxysteroid dehydrogenase

About: Hydroxysteroid dehydrogenase is a research topic. Over the lifetime, 1087 publications have been published within this topic receiving 28468 citations. The topic is also known as: hydroxysteroid dehydrogenase.

New Aspects of Hexobarbital Metabolism: Stereoselective Metabolism, New Metabolic Pathway via GSH Conjugation, and 3‐Hydroxyhexobarbital Dehydrogenases

Abstract: Hexobarbital, a short-acting hypnotic, is metabolized to 3′-hydroxyhexobarbital by cytochrome P450, and then to 3′-oxohexobarbital by liver cytosolic dehydrogenase. New methods of separation for hexobarbital and its metabolites by TLC have been developed and applied to study the metabolism of hexobarbital enantiomers and stereoselective metabolism of hexobarbital. (+)-Hexobarbital preferentially was transformed into β-3′-hydroxyhexobarbital and the (−)-enantiomer preferentially transformed into α-3′-hydroxyhexobarbital by rat liver microsomes. Glucuronidation and dehydrogenation of 3′-hydroxyhexobarbital were also stereoselective and the S-configuration at the 3′-position was preferred. α-3′-Hydroxyhexobarbital from (−)-hexobarbital and the β-isomer from (+)-hexobarbital were shown to be preferentially conjugated with glucuronic acid in rabbit urine, and to be preferentially dehydrogenated to form 3′-oxohexobarbital by rabbit and guinea pig 3-hydroxyhexobarbital dehydrogenases. A new metabolic pathway of hexobarbital was found in which 3′-oxohexobarbital reacts with glutathione to form 1,5-dimethylbarbituric acid and a cyclohexenone-glutathione adduct, a novel metabolite. 1,5-Dimethylbarbituric acid was excreted into the urine and the cyclohexenone-glutathione adduct into the bile of rats dosed with hexobarbital. 3-Hydroxyhexobarbital dehydrogenases that dehydrogenate 3-hydroxyhexobarbital into 3′-oxohexobarbital were purified from the liver cytosol of rabbits, guinea pigs, goats, rats, mice, hamsters, and humans and characterized. These enzymes were monomeric proteins and had molecular weights of about 34500—42000, and used NAD+ and NADP+ as cofactors, except for the human enzyme that had a molecular weight of about 58000 and used NAD+ alone. Each enzyme exhibited its own characteristics. Substrate specificity demonstrated that 3-hydroxyhexobarbital dehydrogenases dehydrogenate not only α,β-unsaturated cyclic and acyclic secondary alcohols but also some 17β-, 3α-hydroxysteroids or both, except for the human enzyme. The amino acid sequence of the hamster enzyme indicated that it belongs to the aldo-keto reductase superfamily and hydroxysteroid dehydrogenase subfamily.

Changes in the Activities of Hydroxysteroid Dehydrogenases in Rabbit and Hamster Oocytes during Meiotic Maturation

Abstract: The activities of hydroxysteroid dehydrogenases (HSDs) were histochemically demonstrated in rabbit and hamster oocytes in the process of maturation, and the changes in steroid metabolism during meiotic maturation were examined. In rabbits, the percentages of oocytes showing the activities of Δ5-3β-HSD (with DHEA as the substrate), 17β-HSD (testosterone) and 20β-HSD (20β-hydroxyprogesterone) were always high and did not change during maturation, whereas those showing the activities of Δ5-3β-HSD (pregnenolone and 17α-hydroxy-pregnenolone), 17 β-HSD (estradiol-17β), 20α-HSD (20 α-hydroxyprogesterone) and 20β-HSD (17α-hydroxyprogesterone) decreased as the time after the hCG injection was prolonged. On the other hand, the activities of Δ5-3β-HSD, 17 β-HSD, 20α-HSD and 20β-HSD with eight substrates were almost always observed in hamster oocytes from 0 to 13 hrs after the hCG injection. The present findings suggested that the metabolic abilities of 20β-hydroxyprogesterone and androgen are constantly present in rabbit oocytes in the process of maturation, whereas those of progesterone, 17α-hydroxyprogesterone, 17α, 20β-dihydroxyprogesterone, 20α-hydroxyprogesterone and estrogen decrease during maturation. And it was also confirmed in hamster oocytes that the metabolic abilities of progesterone, 17α-hydroxyprogesterone, 17α, 20β-dihydroxyprogesterone, 20α-hydroxyprogesterone, 20β-hydroxyprogesterone, estrogen and androgen are always present and do not vary with maturation.

Supplementary Figure Legends 1-2 from 17β-Hydroxysteroid Dehydrogenase Type 12 in Human Breast Carcinoma: A Prognostic Factor via Potential Regulation of Fatty Acid Synthesis

Abstract: Supplementary Figure Legends 1-2 from 17β-Hydroxysteroid Dehydrogenase Type 12 in Human Breast Carcinoma: A Prognostic Factor via Potential Regulation of Fatty Acid Synthesis