Testosterone oxidation

Gemzik, B., Halvorson, M.R. and Parkinson, A. (1990) Pronounced and differential effects of ionic strength and pH on testosterone oxidation by membrane-bound and purified forms of rat liver microsomal cytochrome P-450. Journal of Steroid Biochemistry, 35 (3-4), 429-440. 

Pearce R, Greenway D, Parkinson A (1992) Species differences and interindividual variahon in liver microsomal cytochrome P450 2A enzymes effects on coumarin, dicumarol, and testosterone oxidation. Arch Biochem Biophys 298 211-225 Pelkonen O, Sotaniemi EA, Ahokas JT (1985) Coumarin 7-hydroxylase activity in human hver microsomes. Properties of the enzyme and interspedes comparisons. Br J Clin Pharmacol 19 59-66... 

Silica gel and aluminium oxide layers are highly active stationary phases with large surface areas which can, for example, — on heating — directly dehydrate, degrade and, in the presence of oxygen, oxidize substances in the layer This effect is brought about by acidic silanol groups [93] or is based on the adsorption forces (proton acceptor or donor effects, dipole interactions etc) The traces of iron in the adsorbent can also catalyze some reactions In the case of testosterone and other d -3-ketosteroids stable and quantifiable fluorescent products are formed on layers of basic aluminium oxide [176,195]... 

The ethyl acetate solution is then washed with water, dried and evaporated. To remove any selenium still present, the residue is dissolved in 200 cc of methanol and mixed with 100 g of iron powder and 2 g of active carbon. The mixture is heated for 30 minutes with stirring under reflux, then filtered with suction, washed with methanol and the solution evaporated in vacuo. The residue is then chromatographed on 900 g of aluminum oxide. The residues of the evaporated benzene and ether fractions are treated with active carbon in methanol or acetone, evaporated again, and the residue recrystallized from a mixture of acetone and ether. There are obtained 17.5 g of pure 1-dehydro-17a-methyl-testosterone which melts at 163° to 164°C. 

Hydroxy-5-oxo-3,5-seco-4-norandrostane-3-carboxylic acid has been prepared by ozonolysis of testosterone2-4 or of testosterone acetate, followed by alkaline hydrolysis,5 and by the oxidation of testosterone acetate with ruthenium tetroxide.9... 

Testosterone is metaboHzed by two pathways. One involves oxidation at the 17 position, and the other involves reduction of the A ring double bond and the 3-ketone. Metabohsm by the first pathway occurs in many tissues, including liver, and produces 17-ketosteroids that... 

Mooradian (1993) has studied the antioxidant properties of 14 steroids in a non-membranous system in which the fluorescence of the protein phycoerythrin was measured in the presence of a lipid peroxyl radical generator (ABAP). Oxidation of the protein produces a fluorescent species. Quenching of fluorescence by a test compound indicates antioxidant activity. Oestrone, testosterone, progesterone, androstenedione, dehydroepian-drosterone, cortisol, tetrahydrocortisone, deoxycorti-... 

Testosterone also plays a significant albeit complex role in erectile function. Testosterone is responsible for much of a man s libido. With low serum concentrations, libido declines. Additionally, testosterone helps with stabilization of intracavernosal levels of nitric oxide synthase, the enzyme responsible for triggering the nitric oxide cascade. Interestingly, some patients with low or borderline low serum concentrations of testosterone will have normal erectile function, while some with normal levels will have dysfunction. 

A somewhat related sequence leads to trilostane (111), a compound that inhibits the adrenal gland more specifically the agent blocks some of the metabolic responses elicited by the adrenal hormone ACTH in experimental animals. Reaction of the hydroxy-methylene derivative 108, obtained from testosterone, with hydroxylamine gives the corresponding isoxazole (109). Oxidation of the C-4,5 double bond by means... 

MgCl2 (10 mM) increased the apparent Km (83 to 173 /am) and reduced the Vjnax (3.4 to 2.4 min-1) of triazolam 4-hydroxylation by expressed CYP3A4 [21]. However, both MgCl2 (30 mM) and CaCl2 (30 mM) significantly increased reaction rates of testosterone 6/3-hydroxylation (approximately threefold) and nifedipine oxidation (three- to six-fold) by human liver microsomes (HLMs) or recombinant CYP3A4 (reconstituted with b5 and GSH) [15]. It was suggested that divalent cation stimulation on the activity was related to involvement of b5 in CYP 3A4 reaction. 

FIGURE 4.69 Cytochrome P450-catalyzed oxidation of testosterone. 

The reactions presented here must not be confused with oxidative reactions that increase bond order and are catalyzed by oxidoreductases, as discussed elsewhere. Examples of the latter reactions include the cytochrome P450 mediated oxidation of testosterone to 6,7-dehydrotestosterone, and the oxidation of l,2,3,6-tetrahydro-l-methyl-4-phenylpyridine to 2,3-dihydro-1-methy 1-4-phenylpyridinium catalyzed by monoamine oxidase (Chapt. 4 and 9 in [50]). 

Ethanol oxidation, via alcohol dehydrogenase, reduces testosterone secretion, due to a high NADH/NAD ratio is the Leydig cells in the testes. 

An exactly analogous enzymic transformation is encountered during the formation of oestrogen and androgen sex hormones, e.g. estradiol and testosterone respectively, where dehydroepiandrosterone is oxidized to androstenedione. 

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