Comparison of Two Measures of Missing Cofactor in Cofactor-Dependent Enzymes: Proportion Versus Relative Increase

The degree of missing cofactor in a cofactor-dependent enzyme is widely used as a biomarker of cofactor deficiency. The degree of missing cofactor can be expressed either as the proportion of enzyme without cofactor, or as the relative increase in enzyme with cofactor after addition of excess cofactor to the sample. Especially for enzymes with thiamine pyrophosphate (TPP) as a cofactor, the relative increase (TPP-effect) has been used in a majority of studies, and its use seems to prevail without consideration of the proportion (latency) as a better alternative. In this letter, the statistical properties of the two measures are compared in the context of a thiamine-dependent enzyme. Proportion is a more balanced and sensitive measure than relative increase, and simulation shows that proportion is associated with equal or higher statistical power than relative increase. The power difference can be as high as 0.12.