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• W1969497645 abstract "1 The liver DT-diaphorase activity of “warfarin-resistant” rats (rats resistant to anticoagulant drugs) has been investigated. 2 The soluble fraction of liver homogenates of homozygous resistant males exhibits a DT-diaphorase activity about 10 times lower, and that of females about 4 times lower, than normal controls, both on the protein and on the liver-weight basis. In heterozygotes the activity is intermediate between those of homozygous resistant and normal rats. No difference in liver DT-diaphorase activity is found between normal males and females. 3 The lowered DT-diaphorase activity found in liver supernatants of resistant rats is not due to the presence of an endogenous inhibitor, nor to an intracellular distribution of the enzyme different from that found in normal rats. Both the soluble-cytoplasmic and the mitochondrial DT-diaphorase activities are diminished. 4 The liver DT-diaphorase of resistant rats has unchanged Michaelis constants with respect to its substrates NADH and NADPH. Like in the case of the normal enzyme, dicoumarol and warfarin act as competitive inhibitors with respect to the reduced nicotinamide nucleotides, and the Ki values are virtually unaltered. Likewise Tween-20 modifies both enzymes in a similar manner. 5 The difference in DT-diaphorase activity between normal and resistant rats is not paralleled by a comparable difference in the activity of any other of a variety liver enzymes tested. 6 It is concluded that warfarin-resistant rats possess a quantitatively and/or qualitatively altered DT-diaphorase and that the lowered DT-diaphorase activity is responsible for the genetically determined anticoagulant-resistance of the animals. A hypothesis concerning the role of DT-diaphorase in the anticoagulant-sensitive, vitamin K-dependent biosynthesis or activation of certain blood-coagulation proteins is proposed." @default.
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• W1969497645 date "1972-01-01" @default.
• W1969497645 modified "2023-10-13" @default.
• W1969497645 title "A Study of the DT-Diaphorase Activity of Warfarin-Resistant Rats" @default.
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• W1969497645 doi "https://doi.org/10.1111/j.1432-1033.1972.tb01685.x" @default.
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