Alchemy vs. chemistry: the etymological origins of a historiographic mistake.

The parallel usage of the two terms "alchemy" and "chemistry" by seventeenth-century writers has engendered considerable confusion among historians of science. Many historians have succumbed to the temptation of assuming that the early modern term "chemistry" referred to something like the modern discipline, while supposing that "alchemy" pertained to a different set of practices and beliefs, predominantly the art of transmuting base metals into gold. This paper provides the first exhaustive analysis of the two terms and their interlinguistic cognates in the seventeenth century. It demonstrates that the intentional partition of the two terms with the restriction of alchemy to the sense of metallic transmutation was not widely accepted until the end of the seventeenth century, if even then. The major figure in the restriction of meaning, Nicholas Lemery, built on a spurious interpretation of the Arabic definite article al, which he inherited from earlier sources in the chemical textbook tradition. In order to curtail the tradition of anachronism and distortion engendered by the selective use of the terms "alchemy" and "chemistry" by historians, the authors conclude by suggesting a return to seventeenth-century terminology for discussing the different aspects of the early modern discipline "chymistry."

Identification of a warfarin-sensitive protein component in a 200S rat liver microsomal fraction catalyzing vitamin K and vitamin K 2,3-epoxide reduction.

A partially purified, 200S submicrosomal fraction exhibiting thiol-dependent vitamin K1 (vitamin K) and epoxide reductase activities has been isolated by partial solubilization of rat hepatic microsomes with sodium cholate and separation by centrifugation at 105 000 g into a discontinuous sucrose gradient. At pH 7.4, the rates of vitamin K and vitamin K 2,3-epoxide reduction per milligram of 200S fraction protein were equivalent and were 2.5-3.0 times faster than in microsomes. Reduction of vitamin K 2,3-epoxide occurred in a tightly coupled, two-step reaction initially to vitamin K and subsequently to vitamin K hydroquinone (vitamin KH2). Incorporation of glycerol or sucrose and of sodium cholate into reaction mixtures equivalently affected the rates of both vitamin K and vitamin K 2,3-epoxide reduction, but in the case of epoxide metabolism, the ratios of vitamin KH2/vitamin K were much lower, suggesting that the second reaction has been partially uncoupled from the first. A 14 000-17 000-dalton warfarin-sensitive protein (WSP) that participates in vitamin K and vitamin K 2,3-epoxide reduction in the 200S fraction was identified by incorporation of N-[3H]ethylmaleimide ([3H]NEM) into the catalytically active reduced form of one or more attached disulfides. Reduction of WSP with dithiothreitol was required for reaction with [3H]NEM, and the substrates vitamin K and vitamin K 2,3-epoxide and the inhibitor warfarin all effectively blocked the reaction. 2-Mercaptoethanol could not substitute for dithiothreitol.(ABSTRACT TRUNCATED AT 250 WORDS)

Warfarin inhibition of vitamin K 2,3-epoxide reductase in rat liver microsomes.

Warfarin is a potent inhibitor of vitamin K 2,3-epoxide reduction to vitamin K in vitro and in vivo. Dithiothreitol, an in vitro reductant for the vitamin K 2,3-epoxide reductase, antagonizes inhibition of the reductase by warfarin via mechanisms that have not been determined [Zimmermann, A., & Matschiner, J. T. (1974) Biochem. Pharmacol. 23, 1033-1040]. Experiments with rat hepatic microsomes were undertaken to characterize the interactions that exist between vitamin K 2,3-epoxide, warfarin, and dithiothreitol. Increasing concentrations of dithiothreitol decreased inhibition of the reductase by warfarin. When dithiothreitol was present prior to exposure of the reductase to warfarin, there was less inhibition than when the same concentration of dithiothreitol was present after its exposure to warfarin. Moreover, maximum inhibition of the reductase by warfarin occurred at a much slower rate when dithiothreitol was present initially. Inhibition of the reductase by warfarin was greater when the substrate concentration was 100 microM vitamin K 2,3-epoxide than when it was 10 microM epoxide. On the basis of these data, we conclude that (i) dithiothreitol reduces either directly or indirectly a critical disulfide within the reductase that it reoxidized during reduction of the epoxide substrate, (ii) warfarin and vitamin K 2,3-epoxide are not competitive with respect to one another, and (iii) warfarin binding, which produces inhibition, occurs solely to the disulfide form of the reductase. Once it is bound, warfarin inhibits further reduction of the critical disulfide by dithiothreitol. Dithiothreitol therefore antagonizes warfarin by maintaining the reductase in the reduced state.

R- and S-Warfarin inhibition of vitamin K and vitamin K 2,3-epoxide reductase activities in the rat.

Reduction of vitamin K 2,3-epoxide and vitamin K catalyzed by hepatic microsomal enzymes is required for normal, postribosomal, gamma-carboxyglutamate formation in the prothrombin complex Factors II, VII, IX, and X. The R- and S-warfarin enantiomers differentially inhibit (S-warfarin is 2 to 5 times more active) vitamin K function by mechanisms which have not been unambiguously determined. As a step toward determining the physiologically relevant site(s) of warfarin-antivitamin K activity we investigated in Wistar rats the effects of R- and S-warfarin on vitamin K 2,3-epoxide and vitamin K reductase activities and correlated them with effects on plasma concentrations of the Factors II, VII, and X. Based on the results of these studies we conclude that: 1) warfarin inhibition of the vitamin K 2,3-epoxide and vitamin K reductases is essentially irreversible; 2) S-warfarin stereoselectively inhibits both reductases in vivo but not in vitro; 3) the vitamin K reductase which utilizes dithiothreitol as cofactor in vitro is primarily responsible for vitamin K reduction to vitamin K hydroquinone under physiological conditions; 4) warfarin initially inhibits gamma-carboxyglutamate formation by inhibiting simultaneously the vitamin K 2,3-epoxide and vitamin K reductases; and 5) following enantiomer administration there is an apparent lack of correlation between the restoration of the reductase activities and the reinitiation of coagulation factor synthesis.