Histidine Metabolism the Figlu Test

The ability to metabolize a test dose of histidine provides a sensitive functional test of folate nutritional status; as shown in Figure 10.6, formiminoglu-tamate (FIGLU) is an intermediate in histidine catabolism and is metabolized by the tetrahydrofolate-dependent enzyme FIGLU formiminotransferase. In folate deficiency, the activity of this enzyme is impaired, and FIGLU accumulates and is excreted in the urine, especially after a test dose of histidine - the FIGLU test.

Although the FIGLU test depends on folate nutritional status, the metabolism of histidine will also be impaired and a positive result obtained, in vitamin B12 deficiency, because of the secondary deficiency of folate (Section 10.3.4.1). About 60% of vitamin B12-deficient subjects show increased FIGLU excretion after a histidine load.

In experimental animals and with isolated tissue preparations and organ cultures, the test can be refined by measuring the production of 14CO2 from [14C]histidine in the presence and absence of added methionine. If the impairment of histidine metabolism is the result of primary folate deficiency, the addition of methionine will have no effect. By contrast, if the problem is trapping of folate as methyl-tetrahydrofolate, the addition of methionine will restore normal histidine oxidation as a result of restoring the inhibition of methylene-tetrahydrofolate reductase by S-adenosylmethionine and restoring the activity of 10-formyl-tetrahydrofolate dehydrogenase, thus permitting more normal folate metabolism (Section 10.3.4.1).

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