Dehydrogenation of 3-phenoxybenzyl alcohol in isolated perfused rabbit skin, skin homogenate and purified dehydrogenases.
The formation of 3-phenoxybenzoic acid from 3-phenoxybenzyl alcohol was determined in (a) rabbit ears, single-pass perfused with a protein-free buffer, pH 7.4; (b) the microsomal fraction and its supernatant from homogenized rabbit skin; and (c) purified alcohol dehydrogenase from horse liver and baker's yeast. The inhibition of product formation in (a) was about 60% by various 4-methylpyrazole concentrations, but metyrapone had no effect. Following ultracentrifugation, only the supernatant of homogenized skin showed product formation (apparent Vmay: 32 pmol/min per cm2 skin; apparent Km: 64 microM). 3-Phenoxybenzyl alcohol and ethanol dehydrogenation was similar by alcohol dehydrogenase from horse liver (apparent Km: 0.7 vs. 0.4 mM; apparent Vmax: 0.3 vs. 0.2 U/ microg protein). In baker's yeast, the apparent Km of 3-phenoxybenzoic acid formation was several times larger than that for ethanol dehydrogenation. The KI of 4-methylpyrazole for alcohol dehydrogenase from horse liver was 0.6 (3-phenoxybenzyl alcohol) vs. 0.04 microM (ethanol). The KI for ethanol in baker's yeast was 470 microM. In conclusion dehydrogenation is an important metabolic pathway in the skin for xenobiotics with an aliphatic alcohol at a side chain.
Bast
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GE
Walther Straub Institute for Pharmacology and Toxicology, Faculty of Medicine, Ludwig Maximilians University, Munich, Germany.
Kampffmeyer
H G
HG
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000378:metabolism*; D001711:Biotransformation; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009243:NAD / Q000378:metabolism; D009824:Ointments; D010477:Perfusion; D011817:Rabbits; D012867:Skin / Q000201:enzymology* / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D001592:Benzyl Alcohols; D007202:Indicators and Reagents; D009824:Ointments; C064809:3-phenoxybenzylalcohol; D009243:NAD; D003577:Cytochrome P-450 Enzyme System; D000426:Alcohol Dehydrogenase