Effects of induction of rat liver cytosolic aldehyde dehydrogenase on the oxidation of biogenic aldehydes

Biochem Pharmacol. 1986 Dec 15;35(24):4563-9. doi: 10.1016/0006-2952(86)90779-3.

Abstract

Phenobarbital and tetrachlorodibenzo-p-dioxin (TCDD) induce two different forms of aldehyde dehydrogenase (EC 1.2.1.3, ALDH), designated phi and tau respectively, in the rat liver cytosol. The physiological substrates for these enzymes are as yet unknown. In this study we investigated whether the induction of these enzymes forms affected the metabolism of dopamine and norepinephrine in rat liver slices. A 10-fold increase in phi-ALDH produced by phenobarbital treatment resulted in small increases in the formation of 3,4-dihydroxyphenylacetic acid and 3,4-dihydroxymandelic acid from the biogenic amines. The 50- to 100-fold elevation of the tau-isozyme did not alter the rate of formation of the acids. When liver slices were incubated with 40 mM ethanol, the formation of the reduced products of dopamine and norepinephrine, 3,4-dihydroxyphenylethanol and 3,4-dihydroxyphenylglycol, respectively, was favored. Under these conditions, the induction of the phi-isoenzyme again produced only a small increase in the formation of the acid products, whereas the induction of the tau-isoenzyme had no effect on acid production from biogenic amine metabolism. The results suggest that neither the phi- nor the tau-forms of ALDH are involved in the hepatic metabolism of dopamine or norepinephrine and support the conclusion that the oxidation of the aldehyde derived from dopamine occurs in mitochondria [A. W. Tank, H. Weiner and J. Thurman, Biochem. Pharmac. 30, 3265 (1981)].

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / analogs & derivatives
  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Aldehyde Dehydrogenase / biosynthesis*
  • Aldehydes / metabolism*
  • Animals
  • Cytosol / enzymology
  • Dopamine / metabolism*
  • Enzyme Induction / drug effects
  • Ethanol / pharmacology
  • Isoenzymes / biosynthesis*
  • Liver / enzymology*
  • Norepinephrine / metabolism*
  • Phenobarbital / pharmacology
  • Phenylethyl Alcohol / analogs & derivatives
  • Phenylethyl Alcohol / metabolism
  • Polychlorinated Dibenzodioxins / pharmacology
  • Rats

Substances

  • Aldehydes
  • Isoenzymes
  • Polychlorinated Dibenzodioxins
  • 3,4-Dihydroxyphenylacetic Acid
  • 3,4-dihydroxyphenylethanol
  • Ethanol
  • 3,4-dihydroxyphenylacetaldehyde
  • Aldehyde Dehydrogenase
  • Phenylethyl Alcohol
  • Dopamine
  • Norepinephrine
  • Phenobarbital