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FIGURE 4-5 Simulated concentration-dependence curves showing the rate of metabolism of a hypothetical substrate by the common genetic form of an enzyme and two nonsynonymous varrnnts. Variant A exhibits an increased Km and likely reflects a change in the substrate binding site of the protein by the substituted amino acid. Variant B exhibits a change in the maximum rate of metabolism (Vmax) of the substrate. This may be due to reduced expression level of the enzyme or to a decrease in its catalytic efficiency. Altered Km and Vmax may also be coexpressed in a single variant (not shown).

nonsynonymous variants in the coding region need to be refined and tested as predictors of function of SNPs in noncoding regions.

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