Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Aug;82(15):4979–4982. doi: 10.1073/pnas.82.15.4979

Human class I alcohol dehydrogenases catalyze the oxidation of glycols in the metabolism of norepinephrine.

G Mårdh, C A Luehr, B L Vallee
PMCID: PMC390481  PMID: 3161078

Abstract

Investigations of the function of human liver alcohol dehydrogenase (ADH) in norepinephrine metabolism have revealed that class I ADH catalyzes the oxidation of the intermediary alcohols 4-hydroxy-3-methoxyphenyl glycol (HMPG) and 3,4-dihydroxyphenyl glycol (DHPG) in vitro. The kcat/Km values for the individual homogeneous class I isozymes are generally in the range from 2.0 to 10 mM-1 X min-1, slightly lower than those obtained for ethanol oxidation, 16-66 mM-1 X min-1, but considerably higher than those obtained for ethylene glycol oxidation, 0.23-1.5 mM-1 X min-1. Importantly, HMPG and DHPG are not substrates for the class II or class III ADHs. 4-Methylpyrazole and 1,10-phenanthroline inhibit the class I ADH-catalyzed oxidation of HMPG, DHPG, and ethanol with inhibition constants of 75-90 nM and 19-22 microM, respectively, indicating that these substrates interact at the same catalytic site of ADH. Moreover, ethanol inhibits the oxidation of HMPG. The competition of ethanol with HMPG for ADH provides a basis for the in vivo changes observed in norepinephrine metabolism after acute ethanol intake. Any assessment of norepinephrine function through the study of metabolites in peripheral body fluid must include monitoring the oxidation of HMPG by ADH.

Full text

PDF
4979

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blair A. H., Vallee B. L. Some catalytic properties of human liver alcohol dehydrogenase. Biochemistry. 1966 Jun;5(6):2026–2034. doi: 10.1021/bi00870a034. [DOI] [PubMed] [Google Scholar]
  2. Blombery P. A., Kopin I. J., Gordon E. K., Markey S. P., Ebert M. H. Conversion of MHPG to vanillylmandelic acid. Implications for the importance of urinary MHPG. Arch Gen Psychiatry. 1980 Oct;37(10):1095–1098. doi: 10.1001/archpsyc.1980.01780230013001. [DOI] [PubMed] [Google Scholar]
  3. Bosron W. F., Li T. K., Dafeldecker W. P., Vallee B. L. Human liver pi-alcohol dehydrogenase: kinetic and molecular properties. Biochemistry. 1979 Mar 20;18(6):1101–1105. doi: 10.1021/bi00573a026. [DOI] [PubMed] [Google Scholar]
  4. Bühler R., Hempel J., Kaiser R., von Wartburg J. P., Vallee B. L., Jörnvall H. Human alcohol dehydrogenase: structural differences between the beta and gamma subunits suggest parallel duplications in isoenzyme evolution and predominant expression of separate gene descendants in livers of different mammals. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6320–6324. doi: 10.1073/pnas.81.20.6320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davis V. E., Brown H., Huff J. A., Cashaw J. L. Ethanol-induced alterations of norepinephrine metabolism in man. J Lab Clin Med. 1967 May;69(5):787–799. [PubMed] [Google Scholar]
  6. Ditlow C. C., Holmquist B., Morelock M. M., Vallee B. L. Physical and enzymatic properties of a class II alcohol dehydrogenase isozyme of human liver: pi-ADH. Biochemistry. 1984 Dec 18;23(26):6363–6368. doi: 10.1021/bi00321a012. [DOI] [PubMed] [Google Scholar]
  7. Frey W. A., Vallee B. L. Digitalis metabolism and human liver alcohol dehydrogenase. Proc Natl Acad Sci U S A. 1980 Feb;77(2):924–927. doi: 10.1073/pnas.77.2.924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jörnvall H., Hempel J., Vallee B. L., Bosron W. F., Li T. K. Human liver alcohol dehydrogenase: amino acid substitution in the beta 2 beta 2 Oriental isozyme explains functional properties, establishes an active site structure, and parallels mutational exchanges in the yeast enzyme. Proc Natl Acad Sci U S A. 1984 May;81(10):3024–3028. doi: 10.1073/pnas.81.10.3024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lange L. G., Sytkowski A. J., Vallee B. L. Human liver alcohol dehydrogenase: purification, composition, and catalytic features. Biochemistry. 1976 Oct 19;15(21):4687–4693. doi: 10.1021/bi00666a023. [DOI] [PubMed] [Google Scholar]
  10. Lange L. G., Vallee B. L. Double-ternary complex affinity chromatography: preparation of alcohol dehydrogenases. Biochemistry. 1976 Oct 19;15(21):4681–4686. doi: 10.1021/bi00666a022. [DOI] [PubMed] [Google Scholar]
  11. Li T. K., Magnes L. J. Identification of a distinctive molecular form of alcohol dehydrogenase in human livers with high activity. Biochem Biophys Res Commun. 1975 Mar 3;63(1):202–208. doi: 10.1016/s0006-291x(75)80030-1. [DOI] [PubMed] [Google Scholar]
  12. Mårdh G., Anggård E. Norepinephrine metabolism in man using deuterium labelling: origin of 4-hydroxy-3-methoxymandelic acid. J Neurochem. 1984 Jan;42(1):43–46. doi: 10.1111/j.1471-4159.1984.tb09695.x. [DOI] [PubMed] [Google Scholar]
  13. Mårdh G., Sjöquist B., Anggård E. Norepinephrine metabolism in man using deuterium labelling: the conversion of 4-hydroxy-3-methoxyphenylglycol to 4-hydroxy-3-methoxymandelic acid. J Neurochem. 1981 Mar;36(3):1181–1185. doi: 10.1111/j.1471-4159.1981.tb01716.x. [DOI] [PubMed] [Google Scholar]
  14. Parés X., Vallee B. L. New human liver alcohol dehydrogenase forms with unique kinetic characteristics. Biochem Biophys Res Commun. 1981 Jan 15;98(1):122–130. doi: 10.1016/0006-291x(81)91878-7. [DOI] [PubMed] [Google Scholar]
  15. Sjöquist B. Mass fragmentographic determination of 4-hydroxy-3-methoxymandelic acid in human urine, cerebrospinal fluid, brain and serum using a deuterium-labelled internal standard. J Neurochem. 1975 Jan;24(1):199–201. doi: 10.1111/j.1471-4159.1975.tb07652.x. [DOI] [PubMed] [Google Scholar]
  16. Strydom D. J., Vallee B. L. Characterization of human alcohol dehydrogenase isoenzymes by high-performance liquid chromatographic peptide mapping. Anal Biochem. 1982 Jul 1;123(2):422–429. doi: 10.1016/0003-2697(82)90467-5. [DOI] [PubMed] [Google Scholar]
  17. VONWARTBURG J. P., BETHUNE J. L., VALLEE B. L. HUMAN LIVER--ALCOHOL DEHYDROGENASE. KINETIC AND PHYSICOCHEMICAL PROPERTIES. Biochemistry. 1964 Nov;3:1775–1782. doi: 10.1021/bi00899a033. [DOI] [PubMed] [Google Scholar]
  18. Wagner F. W., Burger A. R., Vallee B. L. Kinetic properties of human liver alcohol dehydrogenase: oxidation of alcohols by class I isoenzymes. Biochemistry. 1983 Apr 12;22(8):1857–1863. doi: 10.1021/bi00277a018. [DOI] [PubMed] [Google Scholar]
  19. Wagner F. W., Parés X., Holmquist B., Vallee B. L. Physical and enzymatic properties of a class III isozyme of human liver alcohol dehydrogenase: chi-ADH. Biochemistry. 1984 May 8;23(10):2193–2199. doi: 10.1021/bi00305a014. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES