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.
Highlights
For several decades, researchers measuring the degree of missing cofactor in cofactor-dependent enzymes have predominantly expressed their results as the relative increase in enzyme with cofactor after addition of excess cofactor to the sample
The latency is the proportion of apoenzyme, whereas the thiamine pyrophosphate (TPP)-effect is the relative increase in the amount of active enzyme after excess cofactor addition
In Model 1, latency was associated with higher power than TPP-effect (Table 1), whereas in Model 2, the two measures were associated with equal power (Table 2)
Summary
Researchers measuring the degree of missing cofactor in cofactor-dependent enzymes have predominantly expressed their results as the relative increase in enzyme with cofactor after addition of excess cofactor to the sample. The latency is the proportion of apoenzyme, whereas the TPP-effect is the relative increase in the amount of active enzyme after excess cofactor addition. (For a fixed maximum activity, the TPP-effect is a linear function of the reciprocal of the endogenous activity.) small and large latency values have equal influence on e.g. the arithmetic mean of a sample, whereas large TPP-effect values have higher influence than small TPP-effect values. In this respect, latency is a more balanced measure than TPP-effect. The question may be raised, whether the differences in balance and sensitivity are of any practical importance, e.g. for the statistical power associated with the respective measure
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