Studies of the in vitro oxidation of 1-methyl-4-(1-methylpyrrol-2-yl)-4-piperidinol and its dehydration product 1,2,3,6-tetrahydro-1-methyl-4-(methylpyrrol-2-yl) pyridine by human monoamine oxidases A and B.

Abstract

The ability of highly purified preparations of human monoamine oxidase A and B (MAO A and B) to utilize 1-methyl-4-(1-methylpyrrol-2-yl)-4-piperidinol (MMPP) and its dehydration product 1,2,3,6-tetrahydro-1-methyl-4-(methylpyrrol-2-yl) pyridine (TMMP) as substrates was investigated. The results showed that TMMP was a substrate for both forms of MAO with Km,app values of approximately 60 microM. However, MAO B had a Vmax,app for TMMP about 30-fold greater than MAO A. Additional studies revealed that MMPP was a poor substrate of only MAO B (Km,app = 9.5 mM) and that acid treatment of MMPP led to the formation of a product that could be readily oxidized by both MAO A and B. Similar acid pretreatment of TMMP yielded a product that was a much poorer substrate for MAO B than the parent compound. These results may partially explain why orally administered MMPP produces neurotoxicity in monkeys and TMMP fails to induce chemical parkinsonism.

• Authors: M E Bembenek
• Journal: Life sciences (Life Sci) Vol. 46 Issue 25 Pg. 1873-7 ( 1990) ISSN: 0024-3205 [Print] Netherlands
• PMID: 2362546 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Piperidines
• Pyridines
• 1-methyl-4-(methylpyrrol-2-yl)-1,2,3,6-tetrahydropyridine
• 1-methyl-4-(1-methylpyrrol-2-yl)-4-piperidinol
• Monoamine Oxidase

Topics

• Female
• Humans
• Kinetics
• Liver (enzymology)
• Molecular Structure
• Monoamine Oxidase (metabolism)
• Oxidation-Reduction
• Piperidines (metabolism)
• Placenta (enzymology)
• Pregnancy
• Pyridines (metabolism)
• Spectrophotometry, Ultraviolet
• Substrate Specificity