The interaction of chemical compounds with the functional state of the liver

Abstract

Most of the enzymes which are involved in the biotransformation of chemical compounds are located in the liver. The activities of these enzymes can be altered by a great variety of foreign compounds. Especially lipophilic and relatively stable agents are capable of enhancing the activities of drug-metabolizing enzymes, after chronic exposure, by increasing the amount of these enzymes. Metabolism of foreign compounds generally results in the formation of much less toxic endproducts which can be excreted easily due to their more hydrophilic nature. However it is known that certain chemicals are converted to very toxic compounds which can produce various injuries. Enzyme inducers of course raise the possibility of impairments by accelerating the synthesis of these toxic metabolites. Numerous xenobiotic compounds are also capable of stimulating carbohydrate metabolism via the D-glucuronic acid pathway. In this pathway hexose is converted via UDPglucose, UDPglucuronic acid and D-glucuronic acid into D-glucaric acid, L-ascorbic acid and L-xylulose respectively. It has been demonstrated that at least in the case of short-term treatment a stimulation of the D-glucuronic acid pathway is based on an increased availability of UDPglucose in the liver cell which, in turn, is the result, of an inhibition of glycogen synthesis. Evaluation of the urinary excretion of D-glucaric acid as a reliable nonspecific test for diagnosing exposure to chemical compounds as well as the drug-metabolic capacity, will be the subject of the next article.