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W R Porter

Publications and source records attributed to W R Porter.

34 records · Page 2Linked to original sources
PubMed1982

Dithiobiuret metabolism in the rat.

Our main objective was to describe the metabolism of dithiobiuret (DTB) in the adult, male rat. Based on the thin-layer chromatographic analysis of urine from animals treated ip with 1 mg/kg of [14C] or [35S] labeled DTB, two pathways for metabolism are proposed. One pathway is reversible and involves the oxidation of DTB to thiuret and the reduction of thiuret back to DTB. The other pathway consists of the desulfuration of DTB to monothiobiuret. The liver appears to desulfurate DTB because DTB-derived [35S] was eliminated from the liver more rapidly (T1/2 = 10 hr) than [14C] (T1/2 = 15 hr). The liver was the only tissue where the elimination kinetics of [35S] and [14C] DTB were different. For all extrahepatic tissues examined and plasma, the elimination of DTB-derived [35S] paralleled that of [14C]. The T1/2 for plasma disappearance of both radiolabeled forms of DTB was approximately 10 hr and the cumulative urinary excretion of DTB-derived [35S] and [14C] was parallel and amounted to about 60% of the dose in 24 hr. DTB-derived radioactivity in urine that co-chromatographed with DTB, monothiobiuret, thiuret and sulfate was quantitated along with that of three uncharacterized metabolites. The presence of these unknown metabolites suggests that DTB metabolism is complex. The present study is the first description of the metabolic fate of DTB in the rat and serves as a starting point for determining whether DTB neurotoxicity is caused by the parent compound or a metabolite.

Animals↗
PubMed1978

Conformations of selected 3-substituted 4-hydroxycoumarins in solution by nuclear magnetic resonance. Warfarin and phenprocoumon.

The chemical shift position of the benzylic proton, Hx, has been found to be diagnostic in indicating the preferred conformations of selected 3-substituted 4-hydroxycoumarins. In general, the nonrigid open-chain compounds, e.g., to open-chain tautomer of warfarin and phenprocoumon, are found to exist in equal populations of the two conformations in which the benzylic proton is in the plane of the coumarin ring and is either cis or trans to the 3,4 double bond. The cyclic compounds, e.g., cyclocumoral, are constrained to two limiting conformations defined as axial2 or trans or intermediate conformations between these limits. Evidence is presented that suggests that the antivitamin K activity of warfarin is due to its open side-chain tautomeric form.

4-Hydroxycoumarins↗
PubMed1977

Improved non-parametric statistical methods for the estimation of Michaelis-Menten kinetic parameters by the direct linear plot.

The theoretical basis for the direct linear plot [Eisenthal & Cornish-Bowden (1974) Biochem. J. 139, 715-720], a non-parametric statistical method for the analysis of data-fitting the Michaelis-Menten equation, was reinvestigated in order to accommodate additional experimental designs and to provide estimates of precision more directly comparable with those obtained by parametric statistical methods. Methods are given for calculating upper and lower confidence limits for the estimated parameters, for accommodating replicate measurements and for comparing the results of two separate experiments. Factors that influence the proper design of experiments are discussed.

Kinetics↗
PubMed1977

Structure of warfarin in solution.

Warfarin in solution is shown to consist of three interconverting tautomeric structures, two of which are cyclic diastereomeric hemiketals, while the third and minor component is the open-chain intermediate form. The configurations of all the tautomers as well as the major conformations of the cyclic tautomers are assigned. The assignments are supported by comparison with the chemical shift and coupling constant parameters of structurally fixed model compounds.

Chemical Phenomena↗