Studies on the mechanism of MPTP oxidation by human liver monoamine oxidase B

FEBS Letters

Brossi, Arnold²  Bembenek, Michael E.¹  Fritz, Richard R.¹  Gessner, Wieslaw²  Abell, Creed W.¹ 

[1] Division of Biochemistry, Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77550, USA;Medicinal Chemistry Section, Laboratory of Chemistry, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20205, USA

关键词: 1-Methyl-4-phenyl-1;    2;    3;    6-tetrahydropyridine;    Neurotoxin;    Monoamine oxidase;    (Human liver);    Deuteration;    Oxidation mechanism;   

DOI  :  10.1016/0014-5793(86)81232-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its deuterated analogues were oxidized to their corresponding dihydropyridinium species (MPDP⁺) by preparations of pure human liver MAO B : monoclonal antibody complex to investigate the mechanism of MPTP activation. Lineweaver-Burk plots of initial reaction rates revealed that the K _m,app values for the various deuterated MPTP analogues were similar to those of MPTP. In contrast, V _max,app values were substantially decreased by substitution of deuterium for hydrogen on the tetrahydropyridinium ring, especially at C-6. Deuterium substitution on the N-methyl group alone did not significantly reduce V _max,app. These studies support the interpretation that oxidation of MPTP at the C-6 position on the tetrahydropyridine ring is a major rate-determining step in its biotransformation by MAO B.

【 授权许可】

Unknown