PUBLICATIONS OF WONG KIM PING (1966-1990)

Abstract

Three major Phase II biotransformation processes, namely sulphate conjugation, glucuronide conjugation and N-acetylation form the theme of this D.Sc. thesis. These pathways participate actively in the detoxification of xenobiotics and endobiotics in man and in most mammals. Both sulphate and glucuronide conjugation reactions share common substrates with hydroxyl groups and the conjugates formed are generally less pharmacologically active. In addition, the sulphates and glucuronides are water soluble and strongly acidic and this accounts for their ready excretion in the urine or in the bile or by both routes in varying proportions. Many phenolic substrates of endogenous and exogenous origins have been employed in my studies as acceptors of phenolsulphotransferase (PST) and UDP-glucuronyltransferase (UDPGT). Acetylation, on the other hand is a major route of metabolism of foreign amines. An interesting aspect of N-acetylation in man is the existence of a hereditary polymorphism in the rate of drug metabolism. Thus the general population can be classified as either fast or slow acetylators. The differences are attributable to the activity of N-acetyltransferase (NAT) in the liver. Kinetic studies of these three transferases, together with the enzymes involved in the biosyntheses of the conjugating agents, namely 3'-phosphoadenosine5'-phosphosulphate (PAPS) and uridine diphosphoglucuronic acid (UDPGA) have provided some insight into the mechanism and regulation of cletoxication reactions. My publications in this area of research were listed in chronological order. Publications indicated with one asterisk were conference papers while those with double asterisks were chapters in books. This list has also been reorganised in Table 1 to show my participation in each of these publications. I was the solo author of 20 publications and the principal author in 80% of the publications. About 85% of the work was carried out in NUS. For easy reference to the contents of the papers, they were recompiled and summarised as sulphate conjugation, glucuronide conjugation and N-acetylation in Tables 2,3 and 4, respectively. The chapter on my "Contributions to the advancement of knowledge" in this field of research follows a similar format.