Characterization of brain beta-carboline-2-N-methyltransferase, an enzyme that may play a role in idiopathic Parkinson's disease

被引:24
作者
Gearhart, DA
Neafsey, EJ
Collins, MA
机构
[1] LOYOLA UNIV, MED CTR, DEPT MOL & CELLULAR BIOCHEM, MAYWOOD, IL 60153 USA
[2] LOYOLA UNIV, MED CTR, GRAD PROGRAM NEUROSCI, MAYWOOD, IL 60153 USA
[3] LOYOLA UNIV, MED CTR, DEPT CELL BIOL NEUROBIOL & ANAT, MAYWOOD, IL 60153 USA
关键词
Parkinson's disease; beta-carbolines; S-adenosyl-L-methionine; N-methyltransferase; N-methylation; bovine brain;
D O I
10.1023/A:1027351120616
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The activity of beta-carboline-2-N-methyltransferase results in the formation of neurotoxic N-methylated beta-carbolinium compounds. We have hypothesized that these N-methylated beta-carbolinium cations may contribute to the development of idiopathic Parkinson's disease. This report describes experiments undertaken to optimize assay conditions for bovine brain beta-carboline-2-N-methyltransferase activity. The activity of beta-carboline-2-N-methyltransferase is primarily localized in the cytosol, has a pH optimum of 8.5-9, and obeys Michaelis-Menten kinetics with respect to its substrates, 9-methylnorharman (9-MeNH) and S-adenosyl-L-methionine (SAM). Kinetic constants, K-M and V-max, with respect to 9-MeNH, are 75 mu M and 48 pmol/h/mg protein, respectively. The K-M for SAM is 81 mu M and the V-max is 53 pmol/h/mg protein. In addition, enzyme activity is inhibited by S-adenosyl-L-homocysteine (SAH) or zinc, and is increased 2-fold in the presence of iron or manganese. Enzyme characterization is a prerequisite to the purification of this N-methyltransferase from bovine brain as well as comparison of its activity in human brain from control and Parkinson's disease individuals.
引用
收藏
页码:113 / 121
页数:9
相关论文
共 55 条
[1]   DETERMINATION OF BETA-CARBOLINES IN FOODSTUFFS BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY [J].
ADACHI, J ;
MIZOI, Y ;
NAITO, T ;
YAMAMOTO, K ;
FUJIWARA, S ;
NINOMIYA, I .
JOURNAL OF CHROMATOGRAPHY, 1991, 538 (02) :331-339
[2]  
AIRAKSINEN MM, 1981, MED BIOL, V59, P21
[3]   MITOCHONDRIAL RESPIRATORY INHIBITION BY N-METHYLATED BETA-CARBOLINE DERIVATIVES STRUCTURALLY RESEMBLING N-METHYL-4-PHENYLPYRIDINE [J].
ALBORES, R ;
NEAFSEY, EJ ;
DRUCKER, G ;
FIELDS, JZ ;
COLLINS, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (23) :9368-9372
[4]  
ANSHER SS, 1987, METHOD ENZYMOL, V142, P660
[5]   ROLE OF N-METHYLTRANSFERASES IN THE NEUROTOXICITY ASSOCIATED WITH THE METABOLITES OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) AND OTHER 4-SUBSTITUTED PYRIDINES PRESENT IN THE ENVIRONMENT [J].
ANSHER, SS ;
CADET, JL ;
JAKOBY, WB ;
BAKER, JK .
BIOCHEMICAL PHARMACOLOGY, 1986, 35 (19) :3359-3363
[6]  
ANSHER SS, 1986, J BIOL CHEM, V261, P3996
[7]   HARMAN IN RAT-BRAIN, LUNG AND HUMAN CSF - EFFECT OF ALCOHOL-CONSUMPTION [J].
BOSIN, TR ;
BORG, S ;
FAULL, KF .
ALCOHOL, 1988, 5 (06) :505-511
[8]   HARMAN IN ALCOHOLIC BEVERAGES - PHARMACOLOGICAL AND TOXICOLOGICAL IMPLICATIONS [J].
BOSIN, TR ;
FAULL, KF .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1988, 12 (05) :679-682
[9]   A PRIMATE MODEL OF PARKINSONISM - SELECTIVE DESTRUCTION OF DOPAMINERGIC-NEURONS IN THE PARS COMPACTA OF THE SUBSTANTIA NIGRA BY N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE [J].
BURNS, RS ;
CHIUEH, CC ;
MARKEY, SP ;
EBERT, MH ;
JACOBOWITZ, DM ;
KOPIN, IJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (14) :4546-4550
[10]  
BURNS RS, 1984, CAN J NEUROL SCI, V11, P166