Dehydrogenases hydroxysteroid dehydrogenase

Cortisol-Cortisone Conversion. Under normal conditions, this equilibrium slightly favors the oxidized compound. Similarly, the conversion of corticosterone to 11-deoxycorticosterone is also mediated by the liP-hydroxysteroid dehydrogenase enzyme system and requites NAD(P) /NAD(P)H. This conversion is especially important both in the protection of the human fetus from excessive glucocorticoid exposure, and in the protection of distal nephron mineral ocorticoid receptors from glucocorticoid exposure (14). The impairment of this conversion is thought to result in hypertension associated with renal insufficiency (15). 

A.- ng deduction. This is an irreversible reaction which is a foremost determinant of the secretion rate of cortisol (double bonds and C-3 carbonyl). Catalyzed predominantiy by cortisone P-reductase and 3a-hydroxysteroid dehydrogenases, SP sterols result, although 5a sterols are more prevalent in the case of other glucocorticoids. Urocortisol and urocortisone result from the metabohsm of cortisol and cortisone, respectively. Compounds can be complexed to glucuronic acid at this point. 

C-20 deduction. Two stereoisomers can result from this transformation, although cortisol is thought to act primarily with (R)20P-hydroxysteroid dehydrogenase. This is a first step in the metabohsm of corticosterone. 

Testosterone, the principal male sex steroid hormone, is synthesized in five steps from cholesterol, as shown below. In the last step, five isozymes catalyze the 17/3-hydroxysteroid dehydrogenase reactions that interconvert 4-androstenedione and testosterone. Defects in the synthesis or action of testosterone can impair the development of the male phenotype during embryogenesis and cause the disorders of human sexuality termed male pseudohermaphroditism. Specifically, mutations in isozyme 3 of the 17/3-hydroxysteroid dehydrogenase in the fetal testis impair the for-... 

An impressive indication of the high regioselectivity of hydroxysteroid dehydrogenases (HSHDs) was reported for the oxidation of various hydroxyl groups at the steroid core ofbile acids [26] (Scheme 9.1). The hydroxy-substituents at positions 3, 7, and 12 could be selectively addressed depending on the hydroxysteroid... 

CLIP Corticotropin-hke intermediate lobe peptide OHSD Hydroxysteroid dehydrogenase PNMT Phenylethanolamine-W-methyltransferase ... 

Buur A, N Mprk. (1992). Metabolism of testosterone during in vitro transport across Caco-2 cell monolayers Evidence for beta-hydroxysteroid dehydrogenase activity in differentiated Caco-2 cells. Pharm Res 9 1290-1294. 

Recently, Voogt et al. [91] have reported on the d5-pathway in steroid metabolism of Asterias rubens. These workers established the existence of the d5-pathway (Scheme 20), analogous to the pathway found in mammals this conclusion was based on the observation that radiolabeled cholesterol (1) was converted to pregnenolone (112), 17a-hydroxypregnenolone (141), and androstenediol (142). Labeled pregnenolone was converted additionally to progesterone (129). Androstenediol (142) was the main metabolite of de-hydroepiandrosterone (143), a reaction catalyzed by 17/i-hydroxysteroid dehydrogenase (17/1-HSD). The metabolic conversion of androstenedione (131) to testosterone (132) is also mediated by 17/J-HSD and is related to... 

An IMER immobilizing 3 a-hydroxysteroid dehydrogenase was employed for HPLC determination of cholic acid and a detection limit of 2 pmol was achieved [44], This approach has the advantage of permitting a repeatable use of the enzyme. 

Figure 2 Effect of enzyme immobilization on luminescent image spatial resolution evaluated using coupled enzymatic reactions on nylon net as a model system, (a) Immobilized 3a-hydroxysteroid dehydrogenase (b) immobilized 3a-hydroxysteroid dehydrogenase and FMN-NADH oxidoreductase (c) immobilized 3a-hydroxysteroid dehydrogenase, FMN-NADH oxidoreductase, and bacterial luciferase. (From Ref. 47. Copyright John Wiley Sons Ltd. Reproduced with permission.)...

Seckl,J.R.andWalker,B.R.Minireview liP-Hydroxysteroid dehydrogenase type 1 — A tissue-specific amplifier of glucocorticoid action. Endocrinology 142 1371-1376, 2001. 

Burton, PJ. and Waddell, B.J., Dual function of 1 lP-hydroxysteroid dehydrogenase in placenta Modulating placental glucocorticoid passage and local steroid action, Biol. Reprod., 60, 234, 1999. 

The ALDs are a subset of the superfamily of medium-chain dehydrogenases/reductases (MDR). They are widely distributed, cytosolic, zinc-containing enzymes that utilize the pyridine nucleotide [NAD(P)+] as the catalytic cofactor to reversibly catalyze the oxidation of alcohols to aldehydes in a variety of substrates. Both endobiotic and xenobiotic alcohols can serve as substrates. Examples include (72) ethanol, retinol, other aliphatic alcohols, lipid peroxidation products, and hydroxysteroids (73). 

Davani B, Khan A, Hult M, et al. Type 1 1 lbeta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets. J Biol Chem 2000 275(45) 34841-34844. 

Betz, G., Warren, J. C. Reaction mechanism and stereospecificity of 20 jS-hydroxysteroid dehydrogenase. Arch. Biochem, Biophys. 128, 745—752 (1968). 

Gibb, W., Jeffery, J. Steric, chiral and conformational aspects of the 3-hydroxy- and 20-hydroxysteroid dehydrogenase activities of cortisone reductase preparations. Biochim. Biophys. Acta 268, 13—20 (1972). 

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