Kinetics of Cu2+ inhibition of Na+/K+-ATPase

被引:64
作者
Li, J
Lock, RAC
Klaren, PHM
Swarts, HGP
Stekhoven, FMAHS
Bonga, SEW
Flik, G
机构
[1] CATHOLIC UNIV NIJMEGEN, FAC SCI, DEPT ANIM PHYSIOL, NL-6525 ED NIJMEGEN, NETHERLANDS
[2] CATHOLIC UNIV NIJMEGEN, FAC MED, DEPT BIOCHEM, NL-6525 ED NIJMEGEN, NETHERLANDS
关键词
copper; Na+/K+-ATPase (EC 3.6.1.3); K+-pNPPase; kinetics;
D O I
10.1016/0378-4274(96)03696-X
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The interaction of Cu2+ With enzymatic activity of rabbit kidney Na+/K+-ATPase was studied in media with buffered, defined free Cu2+ levels. The IC50-values are 0.1 mu mol/l for Na+/K-ATPase and 1 mu mol/l for K+-pNPPase. Dithiothreitol (DTT) reverses the inhibitory effect of Cu2+ in vitro. Cu2+ exerts non-competitive effects on the enzyme with respect to Na+, K+, ATP or pNPP, but has a mixed-type inhibitory effect with respect to Mg2+. It is concluded that the appreciation of the inhibitory effect of CU2+ on this enzyme requires carefully composed assay media that include a buffer for Cu2+, and that the IC50-values calculated according to this model indicate that CU2+ may be more toxic than previously anticipated.
引用
收藏
页码:31 / 38
页数:8
相关论文
共 30 条
[1]   PROTECTION AGAINST CADMIUM TOXICITY AND ENZYME-INHIBITION BY DITHIOTHREITOL [J].
AHAMMADSAHIB, KI ;
JINNA, RR ;
DESAIAH, D .
CELL BIOCHEMISTRY AND FUNCTION, 1989, 7 (03) :185-192
[2]  
[Anonymous], 1964, SPECIAL PUBLICATION
[3]   NA+,K+-ATPASE - LIGAND-INDUCED CONFORMATIONAL TRANSITIONS AND ALTERATIONS IN SUBUNIT INTERACTIONS EVIDENCED BY CROSS-LINKING STUDIES [J].
ASKARI, A ;
HUANG, W ;
ANTIEAU, JM .
BIOCHEMISTRY, 1980, 19 (06) :1132-1140
[4]   COPPER TOXICITY IN CULTURED HUMAN SKELETAL-MUSCLE CELLS - THE INVOLVEMENT OF NA+/K+-ATPASE AND THE NA+/CA2+-EXCHANGER [J].
BENDERS, AAGM ;
LI, J ;
LOCK, RAC ;
BINDELS, RJM ;
BONGA, SEW ;
VEERKAMP, JH .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1994, 428 (5-6) :461-467
[5]   STUDIES ON SODIUM-POTASSIUM-ACTIVATED ADENOSINE TRIPHOSPHATASE .1. QUANTITATIVE DISTRIBUTION IN SEVERAL TISSUES OF CAT [J].
BONTING, SL ;
HAWKINS, NM ;
SIMON, KA .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1961, 95 (03) :416-&
[6]   EFFECT OF COPPER ON MEMBRANE ENZYMES [J].
BOWLER, K ;
DUNCAN, CJ .
BIOCHIMICA ET BIOPHYSICA ACTA, 1970, 196 (01) :116-&
[7]  
BUTK, 1982, BIOCHIM BIOPHYS ACTA, V685, P203
[8]   INHIBITION OF RAT-BRAIN MICROSOMAL NA+/K+-ATPASE AND OUABAIN BINDING BY MERCURIC-CHLORIDE [J].
CHETTY, CS ;
RAJANNA, B ;
RAJANNA, S .
TOXICOLOGY LETTERS, 1990, 51 (01) :109-116
[9]  
JORGENSEN PL, 1974, BIOCHIM BIOPHYS ACTA, V356, P815
[10]   SULFHYDRYL-REACTIVE HEAVY-METALS INCREASE CELL-MEMBRANE K+ AND CA-2+ TRANSPORT IN RENAL PROXIMAL TUBULE [J].
KONE, BC ;
BRENNER, RM ;
GULLANS, SR .
JOURNAL OF MEMBRANE BIOLOGY, 1990, 113 (01) :1-12