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

Abstract

The degree of missing cofactor in a cofactor-dependent enzyme is widely used as a biomarker of cofactor defi- ciency. The degree of missing cofactor can be expressed either as the proportion of enzyme without cofactor, or as the rel- ative increase in enzyme with cofactor after addition of excess cofactor to the sample. Especially for enzymes with thia- mine 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 bal- anced and sensitive measure than relative increase, and simulation shows that proportion is associated with equal or high- er statistical power than relative increase. The power difference can be as high as 0.12.