Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By using cell-free preparations of rat liver it was shown that the removal of the 14alpha-methyl group (C-32) of steroids containing either a delta7(8) or a delta8(9) double bond is attended exclusively by the formation of the corresponding 7,14- and 8,14-dienes respectively (structures of types III and VIII). Cumulative evidence from a variety of experimental approaches had led to the deduction that delta8(14)-steroids are not involved as intermediates on the major pathway of cholesterol biosynthesis. The metabolism of [32-3H]lanost-7-ene-3beta,32-diol (structure of type I) results in the formation of radioactive formic acid, no labelled formaldehyde being formed. By using appropriately labelled species of the compound (I) it was found that the release of formic acid and the formation of 4,4-dimethylcholesta-7,14-dien-3beta-ol (strurcture of type III) were closely linked processes, and that in the conversion of compound (I) into compound (III), 3-beta-hydroxylanost-7-en-32-al (II) is an obligatory intermediate. Both the conversion of lanost-7-ene-3beta,32-diol (I) into 3beta-hydroxylanost-7-en-32-al (II) and the further metabolism of the latter (II) to 4,4-dimethylcholesta-7,14-dien-3beta-ol (III) exhibited a requirement for NADPH and O2. This suggests that the oxidation of the 32-hydroxy group of compound (I) to the aldehyde group of compound (II) does not occur by the conventional alcohol dehydrogenase type of reaction, but may proceed by a novel mechanism involving the intermediacy of a gem-diol. A detailed overall pathway for the 14alpha-demethylation in cholesterol biosynthesis is considered, and proposals about the mechanism of individual steps in the pathway are made.
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PMID:Chemical and enzymic studies on the characterization of intermediates during the removal of the 14alpha-methyl group in cholesterol biosynthesis. The use of 32-functionalized lanostane derivatives. 2 46

Six alkylnitrosamino ethanols (R-N(NO)-CH2CH2OH; R = Me, nBu, sBu, iBu, tBu, HOCH2CH2-), including the potent carcinogen N-nitrosodiethanolamine, have been shown to undergo efficient liver alcohol dehydrogenase catalyzed oxidation to their corresponding alpha-nitrosamino aldehydes. Five structurally representative nitrosamino-ethanals (R-N(NO)CH2CHO, R = 4-ClC6H4-, CH3-, nBu-, tBu-, HOCH2CH2-) have been synthesized. Each of these compounds demonstrates the unusual property of facile transnitrosation to a secondary amine. Transnitrosation to dimethylamine, pyrrolidine, morpholine and N-methylaniline has been shown. This reaction occurs rapidly at room temperature in organic solvents but is somewhat slower in aqueous buffer due to extensive equilibrium formation of gem diols by hydration of the aldehyde group. In aqueous media the transnitrosation rate increases with increasing pH from 7 to 9 and does not occur at pH 4. Transnitrosation to primary amines results in deamination (benzylamine----benzyl alcohol). The transnitrosation reaction is accompanied by the formation of imines of glyoxal (R - N = CH - CH = N - R) which appear as primary amines and glyoxal in aqueous solution. Other products have also been characterized as well. These chemical and biochemical data, taken together with results in other laboratories, provide strong support for our hypothesis that certain beta-oxidized nitrosamines can be activated to proximate or ultimate carcinogens by biochemical oxidation to produce highly reactive nitrosamines.
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PMID:Nitroso transfer from alpha-nitrosamino aldehydes: implications for carcinogenesis. 359 27