HKr

The HKr (HK-ratio) is composed of HK and the four kynurenines that are products of the pyridoxal 5´-phosphate (PLP)-dependent enzymes, kynurenine transaminase (KAT) and kynureninase (KYNU). Specifically, HKr is HK:(KA+AA+XA+HAA). This is an extension, or further development, of the HK:XA index as a functional marker of B6 status (2). The principle behind HKr is the same as for other ratio-based functional markers. When vitamin deficiency affects the catalytic capacity (k_cat) of an enzyme, the reponse, which will also serve to maintain flux through the enzyme(s), is an increase in upstream metabolites concomitant with a decrease in downstream metabolites. Thus, an index, like the HKr, for capturing such information is most efficient when it includes both upstream and downstream metabolites. The HKr shows a particularly steep inverse association with PLP at concentrations less than 20 nmol/L, serving as a concrete metabolic confirmation of a cutoff of 20 nmol/L for vitamin B6 deficiency. However, a notable increase in HKr in the interval from 40 to 20 nmol/L PLP also supports a concept of marginal vitamin deficiency in this interval. Compared to the index that only included XA as the downstream metabolite (HK:XA), HKr demonstrate better specificity, sensitivity and reproducibility across cohorts (3).
Method: LC-MS/MS