Conjugation Phenotyping

JV-Acetyltransferases (NATs) catalyze the conjugation of an acetyl group from acetyl-CoA on to an amine, hydrazine or hydroxylamine moiety of an aromatic compound. NATs are involved in a variety of phase II-diug metabolizing processes. There are two isozymes NAT I and NAT II, which possess different substrate specificity profiles. The genes encoding NAT I and NAT II are both multi-allelic. Especially for NAT II, genetic polymoiphisms have been shown to result in different phenotypes (e.g., fast and slow acetylators). 

There is no information regarding the metabolism of 3,3 -dichlorobenzidine in children. However, N-acetylation (as discussed above) in humans is likely done by one of two families of N-acetyltransferases. One of these families, NAT2, is developmentally regulated (Leeder and Kearns 1997). Some enzyme activity can be detected in the fetus by the end of the first trimester. Almost all infants exhibit the slow acetylator phenotype between birth and 2 months of age. The adult phenotype distribution is reached by the age of 4-6 months, whereas adult activity is found by approximately 1-3 years of age. Also, UDP-glucuronosyltransferase, responsible for the formation of glucuronide conjugates, seems to achieve adult activity by 6-18 months of age (Leeder and Kearns 1997). These data suggest that metabolism of 3,3 -dichlorobenzidine by infants will differ from that in adults in extent, rate, or both. 

Fluorescein Fluorescein is a fluorescent dye that can be readily linked to proteins and that is therefore useful, when conjugated to specific antibodies, for lighting up cells with particular phenotypes. It is sometimes abbreviated as FITC because fluorescein isothiocyanate is the chemically active form of the molecule that is used in the conjugation process. 

The passage from one step to the next along the continuum will often depend on a person s characteristics. A biomarker that allows the assessment of a person s susceptibility to alter the progression along the continuum is called a biomarker of susceptibility. Examples are enzymatic genotypes and phenotypes, such as those seen with glutathione-S-transferase M, a phase II conjugation enzyme that often contributes to the detoxification of some electrophilic compounds (Perbellini et al. 2002). 

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