A kinetic study on the phenothiazine dependent oxidation of NADH by bovine ceruloplasmin.
Tranquillizing drugs of the phenothiazine class form charge-transfer complexes with a ceruloplasmin-Cu(II) ion [De Mol NJ. 1985 Biochim Pharmacol 34, 2605-2609], the interaction resulting in a stimulatory effect on the ceruloplasmin catalyzed oxidation of catecholamines and NADH; the latter used as substrate in the present study. A good correlation between stability of the enzyme-drug complex and electron donor ability of the phenothiazine molecule was obtained for drugs with an aliphatic propyl side chain in 10-position (promazine > chlorpromazine > triflupromazine). The hydrofobic methyl group in the side chain of levomepromazine appeared to reduce the stability. A simple correlation between specific efficiency of the enzyme-drug complex and electron donor ability was not obtained (chlorpromazine > promazine = levomepromazine > triflupromazine). The Km-values, characterizing the reaction between NADH and the different enzyme-drug complexes, were estimated. The data suggest that the enzyme-chlorpromazine complex has the best affinity for NADH. The stimulatory effect of levomepromazine closely followed that of promazine.
Løvstad
Rolf A
RA
Department of Medical Biochemistry, Institute Group of Basic Medical Sciences, University of Oslo, PO Box 1112, Blindern, N-0317, Oslo, Norway. rolf.lovstad@basalmed.uio.no
D000818:Animals; D002384:Catalysis; D002395:Catecholamines / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D002570:Ceruloplasmin / Q000737:chemistry*; D003300:Copper / Q000737:chemistry; D007700:Kinetics; D009243:NAD / Q000737:chemistry*; D010084:Oxidation-Reduction; D010640:Phenothiazines / Q000737:chemistry*; D013329:Structure-Activity Relationship
D002395:Catecholamines; D010640:Phenothiazines; D009243:NAD; D003300:Copper; D002570:Ceruloplasmin