Histidine Metabolism - the FIGLU Test

Although the FIGLU test depends on folate nutritiontd status, the metaholism of histidine will also be impeured emd a positive result obtained, in vitamin B12 deficiency, because of the secondary deficiency of folate (Section 

About 60% of viteimin Bi2-deficient subjects show increased FIGLU excretion eifter a histidine load. 

In experimental animals and with isolated tissue preparations and organ cultures, the test can be refined by measuring the production of G02 from [ C]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 wUl 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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The ability to metabolize a test dose of histidine provides a sensitive functional test of folate nutritional status as shown in Figure 10.6, forrnirninoglu-tamate (FIGLU) is an intermediate in histidine catabolism and is metabolized by the tetrahydrofolate-dependent enzyme FIGLU forrnirninotransferase. 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. 

Figure 11.24 Metabolism of histidine — the FIGLU test for folate status.

An in vivo test for the investigation of suspected folic acid deficiency. The normal metabolism of histidine contains a step in which formiminoglutamic acid (FIGLU) is converted to glutamate by an enzyme which uses folate as a cofactor. In patients with folate deficiency, administration of oral histidine results in a greater than normal urinary excretion of FIGLU. 

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