ABSTRACT
A single administration to rats of cyanamide (60 mg/kg, for 1 hour) was found to decrease the contents of cysteate, serine, glutamate, glycine, alanine, valine, methionine, isoleucine, tyrosine, ethanolamine, ornithine and histidine that may be considered as a manifestation on the drug hepatotoxicity. The activities of transaminases, glutamate dehydrogenase, pyruvate dehydrogenase remained unchanged. Cyanamide effects were considerably abolished by the supplementary ethanol administration (0.5 g/kg). Cyanamide failed to affect vitamin-dependent enzymes reflecting thiamine pyrophosphate, pyridoxal phosphate and flavine adenine dinucleotide status of the rat organism.
Subject(s)
Amino Acids/drug effects , Brain/drug effects , Cyanamide/toxicity , Liver/drug effects , Amino Acids/metabolism , Animals , Brain/metabolism , Drug Interactions , Ethanol/toxicity , Liver/metabolism , Male , RatsABSTRACT
The molecula-kinetic parameters (Km, Ki) of three thiamine enzymes, e. g. thiamine pyrophosphokinase (EC 2.7.6.2), pyruvate dehydrogenase (EC 1.2.4.1) and transketolase (EC 2.2.1.1) with respect to the effects of the thiamine antimetabolite hydroxythiamine in the whole animal organism have been compared. It has been shown that only the first two enzymes, which interact competitively with the vitamin, antivitamin or their pyrophosphate ethers, obey the kinetic parameters obtained for the purified enzymes in vitro. The anticoenzymic effect of hydroxythiamine pyrophosphate with respect to transketolase is not observed in vivo at maximal concentration of the anticoenzyme in tissues due to the absence of competitive interactions with thiamine pyrophosphate. The incorporation of the true and false coenzymes into transketolase occurs only during de novo transketolase synthesis (the apoform is absent in tissues, with the exception of erythrocytes) and proceeds slowly with a half-life time equal to 24--30 hrs. After a single injection of hydroxythiamine at a large dose (70--400 mg/kg) the maximal inhibition of the transketolase activity in tissues (liver, heart, kidney, muscle, spleen, lungs adrenal grands) manifests itself by the 48th--72nd hour, when the concentration of free hydroxythiamine and its pyrophosphate is minimal and the whole anticoenzyme is tightly bound to the protein, forming the false holoenzyme. The use of hydroxythiamine for inhibition of pyruvate dehydrogenase or transketolase in animal organism is discussed.
Subject(s)
Oxythiamine/pharmacology , Phosphotransferases/metabolism , Pyruvate Dehydrogenase Complex/metabolism , Thiamin Pyrophosphokinase/metabolism , Thiamine/pharmacology , Thiazoles/pharmacology , Transketolase/metabolism , Animals , Binding, Competitive , Erythrocytes/enzymology , Kinetics , Rats , Tissue DistributionABSTRACT
The influence of thiochrome on the lipids metabolism in animals fed on a usual vivarium ration or synthetic thiamine-free diet carrying as a fat component 18 per cent of oleic acid was investigated. Under conditions of an ordinary vivarium ration thiochrome acted as a weak antivitamin and changed the lipids metabolism rates, like this is done by oxythiamine. When superimposed on an oleate-containing, thiochrome displayed a slightly pronounced vitaminic properties, while its influence on the individual study lipids metabolism rates was somewhat similar to that exerted by thiamine. It is suggested that the effect of thiochrome on the lipids metabolism is not related to the coenzymatic function of thiamine.
