Polymorphically expressed enzymes

Fig. 13.1 Pathways of thiopurine metabolism. The positions of two polymorphically expressed enzymes, TPMT (thiopurine methyl transferase) and ITPA (inosine triphosphate pyrophosphatase), are shown. HGPRT, hypoxanthine guanine phosphoribosyl transferase 6-TIDP, 6-thioi-nosine diphosphate 6-TIMP, 6-thioinosine monophosphate 6-TITP, 6-thio inosine trinophosphate...

Table 1 The Relationship Between Genotype and Phenotype for a Polymorphically Expressed Enzyme with Active (wt), Partially Active ( x), and Inactive ( y) Alleles... 

Alternatively, the last CYP2C enzyme, CYP2C19, is a polymorphically expressed CYP enzyme, where the population is divided into extensive metabolizer (EM) and poor metabolizer (PM) phenotypes, the latter expressing less active or completely inactive enzyme. This polymorphism has a large ethnic component, with the... 

ITABLE 14.1. Some polymorphically expressed metabolic enzymes and transporters that may be amenable to genotype analysis for individualization of drug regimens... 

Polymorphic expression of xenobiotic-metabolizing enzyme systems clinical implications... 

A simple way of evaluating the affect of a single nucleotide polymorphism on enzyme function is to perform transient transfection assays in COS-1 cells. Western blot analysis, with anti-UGTl A antibody, is used to determine protein expression levels of the variants, which often correlate with protein stability. Enzyme kinetic analysis is used to investigate the functional impact of amino acid substitutions. 

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