16/3-Hydroxysteroid , oxidation

This heme-thiolate-dependent enzyme [EC 1.14.15.4], also known as steroid 11/3-monooxygenase, catalyzes the reaction of a steroid with reduced adrenal ferredoxin and dioxygen to produce an 11/3-hydroxysteroid, oxidized adrenal ferredoxin, and water. The enzyme also catalyzes the hydroxylation of steroids at the 18-position and can catalyze the conversion of 18-hydroxycorticosterone into aldosterone. 

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). 

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... 

Dinitrobenzenesulfenyl chloride is a versatile analytical reagent for the characterization of a wide variety of organic compounds, including alcohols, mercaptans, ketones, olefins, amines, aromatic compounds, olefin oxides, and hydroxysteroids. Review articles summarize these applications.9 10... 

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). 

The enzyme 3a-hydroxysteroid dehydrogenase plays a key role in this transport across the hepatocyte. A particularly elegant experiment demonstrated the role of the 3a-hydroxysteroid dehydrogenase, by using [ H] at the 3p hydrogen to show cyclical oxidation-reduction of the 3a-hydroxyl with no accumulation of 3-keto bile acids. Confirmation was obtained by use of indo-methacin, an inhibitor of 3a-hydroxysteroid dehydrogenase, which decreased... 

Acetyl-17-hydroxysteroids on oxidation with IBD lead to the formation of spiro-oxetan-3-ones. The reaction proceeds through an intermediate of the type 31, which undergoes intramolecular cyclization involving participation of the C17-OH group (85S1129) (Scheme 12). 

Reactions catalyzed by 11 (3-hydroxysteroid and 17(3-hydroxysteroid dehydrogenases, (a) 11 (3-hydroxysteroid dehydrogenase type 1, an NADPH-dependent enzyme, catalyzes the conversion of the inactive steroid, cortisone, to cortisol, which is the biologically active glucocorticoid. 11 (3-hydroxysteroid dehydrogenase type 2, an NAD+-dependent enzyme, catalyzes the reverse direction, (b) 17(3-hydroxysteroid dehy-drogenase type 1, an NADPH-dependent enzyme, catalyzes the reduction of estrone to estradiol. Type 2, an NAD+-dependent enzyme, catalyzes the oxidation of estradiol to estrone. Type 3, an NADPH-dependent enzyme, catalyzes the reduction of androstene dione to testosterone. Type 4, an NAD+-dependent enzyme, catalyzes the oxidation of estradiol to estrone, and androstenediol to dehydroepiandrosterone. 

In 3/i-hydroxysteroid-A5-oxidoreductase deficiency, 7a-hydroxycholesterol undergoes side-chain oxidation, producing 3/l,7a-dihydroxy-5-cholenoic acid and... 

An enzyme reactor with immobilized 3 -hydroxysteroid dehydrogenase has been successfully used for the analysis of residues of 17 -methyltestosterone in trout by high-performance liquid chromatography (HPLC) (269). Following their separation by reversed-phase chromatography, the major tissue metabolites of 17 -methyltestosterone, namely 5 -androstane-17 -methyl-3, 17 -diol, and 5 -androstane-17 -methyl-3, 17 -diol, were enzymatically modified in the presence of a coreactant, nicotinamide-adenine dinucleotide (NAD), to the corresponding ketone. The position at 3 was enzymatically oxidized, and NADH, the reduced form of NAD, was produced as a coproduct and subjected to fluorescence detection. Reoxidation of NADH to NAD provides the possibility for electrochemical detection. 

A microsomal retinol dehydrogenase catalyzes the oxidation of CRBP-hound all-trans-retinol to retinaldehyde it also acts as a 3a-hydroxysteroid dehydrogenase. A similar enzyme catalyzes the oxidation of 9-cis- and 11-ds-retinol, but not all-trans-retinol again, it has 3a-hydroxysteroid dehydrogenase activity. In the eye, the major product of this enzyme is 11-cts-retinaldehyde, whereas in other tissues it is 9-cts-retinaldehyde, which is then oxidized to 9-cis-retinoic acid (Section 2.3.2.1 Chen et al., 2000 Duester, 2000, 2001 Gamble et al., 2000 NapoU, 2001). Although there is known to be an isomerase in the eye for the formation of 11-cts-retinaldehyde as a... 

The saxl (hypersensitive to abscisic acid and auxin) mutant probably has a defect in the oxidation and isomerization of 3p-hydroxy-A precursors to 3-oxo-A steroids (Ephritikhine et ah, 1999). AtHSDl (At5g50600) encodes a protein with homology to animal ll- 3-hydroxysteroid dehydrogenase (Li et ah, 2007) however, no obvious sequence similarities exist with the 3P-HSD involved in cardenolide bios)mthesis (see Section 6.3.1.2). 

Oxidation of alcohols. Grob and Schmid used /-butyl hypochlorite in carbon tetrachloride or ether in the presence of pyridine for oxidation of cyclohexanol to cyclohexanone and of /i-butanol to //-butyl butyrate. Ginsburg et aU oxidized 3-hydroxysteroids by dropwise addition of /-butyl hypochlorite in CCli to a solution of the steroid in CCl, at room temperature. When the ketone was to be chlorinated as formed, the reaction was done in acetic acid at followed by heating on the steam bath. Levin et al. obtained 3-ketosteroids in high yield by oxidation of the 3-atcohols with /-butyl hypochloride in dry /-butanol. 

Steroid 649-oxides. Akhtar and Barton found that when a mixture of the reagent and a 5o -bromo-6/3-hydroxysteroid is irradiated with a high-pressure mercury arc lamp a 6,19-oxide can be obtained in 60-80% yield. Light is required. Thus, in the... 

Mercuric oxide-iodine. This combination has been used as a possibly superior alternative to the lead tetraacetate-iodine reagent for oxidative attack of angular methyl groups. Thus a 6j8-hydroxysteroid (1) reacts with mercuric oxide and iodine in a light-induced reaction to give the 6,19-oxide (2) through an intermediate hypoiodite. ... 

Baeyer-VilUger Oxidation. An example is the oxidation of a 20-ketosteroid and hydrolysis of the product to produce the corresponding 17 -hydroxysteroid. ... 

Sondheimer, Amendolla, and Rosenkranz found that cholesterol and other homoallylic A -3-hydroxysteroids are oxidized by active MnOj in refluxing benzene for 8 hrs. to A - -3-ketosteroids, but the yields are too low for preparative purposes. CH.I... 

The degradation of cholesterol leads to the production of bile acids which are structurally closely related to various steroid hormones. (3-Hydroxysteroid dehydrogenase (EC 1.1.1.51) catalyzes the NAD+-de-pendent oxidation of 3(3-, 17(3- and some l6(3-hydroxysteroids to the respective ketosteroids. The enzyme has been adsorbed on a carbon electrode modified by NMP+TCNQ and the NADH liberated in the reaction oxidized anodically (Albery et al., 1987a). Campanella et al. (1984) employed an enzyme sequence electrode composed of NAD+-de-pendent steroid dehydrogenase and horseradish peroxidase for assay of 7a-hydroxysteroids. 

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