Kynureninase tryptophan load test

Figure 9.4. Tryptophan load test for vitamin Be status. Tryptophan dioxygenase, EC 1.13.11.11 formylkynurenine formamidase, EC 3.5.1.9 kynurenine hydroxylase, EC 1.14.13.9 kynureninase, EC 3.7.1.3 kynurenine oxoglutarate aminotransferase, EC 2.6.1.7 andkynurenine glyoxylate aminotransferase, 2.6.1.63. Relative molecular masses (Mr) tryptophan, 204.2 kynurenine, 208.2 3-hydroxykynurenine, 223.2 kynurenic acid, 189.2 and xanthurenic acid, 205.2.

Xanthurenic and kynurenic acids, and kynurenine and hydroxykynurenine, are easy to measure in urine, so the tryptophan load test (the ability to metabolize a test dose of 2—5 g of tryptophan) has been widely adopted as a convenient and very sensitive index of vitamin nutritional status. However, because glucocorticoid hormones increase tryptophan dioxygenase activity, abnormal results of the tryptophan load test must be regarded with caution, and cannot necessarily be interpreted as indicating vitamin B deficiency. Increased entry of tryptophan into the pathway will overwhelm the capacity of kynureninase, leading to increased formation of xanthurenic and kynurenic acids. Similarly, oestrogen metabolites inhibit kynureninase, leading to results that have been misinterpreted as vitamin B deficiency. 

Inhibition of kynureninase (e.g., by estrogen metabolites) also results in accumulation of kynurenine and hydroxykynurenine, and hence increased formation of kynurenic and xanthurenic acids, again giving results which falsely suggest vitamin Bg deficiency. This has been widely, but incorrectly, interpreted as estrogen-induced vitamin Bg deficiency it is in fact simple competitive inhibition of the enzyme that is the basis of the tryptophan load test by estrogen metabolites. 

Diagnostic tests (a) Measure plasma concentration of Bg (b) Measure urinary excretion of xanthurenate (yellow product) following an oral load of tryptophan. Normally tryptophan catabolism proceeds via the Bg-dependent kynureninase but In Bg deficiency, xanthurenate accumulates... 

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