TY - JOUR
T1 - Effect of the locus of the oxygen atom in amino ethers on the inactivation of monoamine oxidase B
AU - Yelekçi, Kemal
AU - Silverman, Richard B.
N1 - Funding Information:
We are grateful to NATO (Grant No.SA.5-2-05(CRG.960155)388/96/ JARC-501), to the National Institutes of Health (GM32634) (R.B.S.), and to the Marmara University Research Fund (K.Y.) for financial assistance.
PY - 1998
Y1 - 1998
N2 - Monoamine oxidase is a flavoenzyme that catalyzes the oxidation of a variety of primary, secondary, and tertiary amines. Although primary alkylamines, such as heptylamine, and primary arylalkyl amines, such as phenylethylamine, are excellent substrates for MAO, their analogues having an electron withdrawing group near the aminomethyl methylene group (1-8) are known to inactivate the enzyme. Inactivation has been attributed to the inductive effect of the electron-withdrawing group of these analogues. To determine the extent of the proposed inductive effect of a heteroatom on MAO B inactivation, a series of oxahrptyiamine analogues (9-12) were synthesized and tested as inactivators of MAO B. The analogues in which the oxygen atom is closest to the alpha-carbon (9 and 10) inactivate MAO B, but activity slowly returns with time. The analogues with the oxygen atom farther from the alpha-carbon inactivate the enzyme, but activity rapidly returns. These results support the inductive effect hypothesis for inactivation.
AB - Monoamine oxidase is a flavoenzyme that catalyzes the oxidation of a variety of primary, secondary, and tertiary amines. Although primary alkylamines, such as heptylamine, and primary arylalkyl amines, such as phenylethylamine, are excellent substrates for MAO, their analogues having an electron withdrawing group near the aminomethyl methylene group (1-8) are known to inactivate the enzyme. Inactivation has been attributed to the inductive effect of the electron-withdrawing group of these analogues. To determine the extent of the proposed inductive effect of a heteroatom on MAO B inactivation, a series of oxahrptyiamine analogues (9-12) were synthesized and tested as inactivators of MAO B. The analogues in which the oxygen atom is closest to the alpha-carbon (9 and 10) inactivate MAO B, but activity slowly returns with time. The analogues with the oxygen atom farther from the alpha-carbon inactivate the enzyme, but activity rapidly returns. These results support the inductive effect hypothesis for inactivation.
KW - Covalent enzyme adduct
KW - Inactivation
KW - Inductive effect
KW - Monoamine oxidase B
KW - Oxaheptylamines
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U2 - 10.3109/14756369809035825
DO - 10.3109/14756369809035825
M3 - Article
C2 - 9879512
AN - SCOPUS:0031958528
SN - 8755-5093
VL - 13
SP - 31
EP - 39
JO - Journal of Enzyme Inhibition
JF - Journal of Enzyme Inhibition
IS - 1
ER -