Histidine loading test

Folate status can be assessed by the measurement of serum or red blood ceil folate levels, by the histidine load test, and by hematological methods. 

The histidine load test is not used in the clinical setting and is only sometimes used by researchers however, a description of this test provides a clear-cut example of how folates behave in the mediation of 1-carbon metabolism. Histidine catabolism takes place in the liver according to the pathway sho vn (Figures 9.16 and 9.17). The intermediates, formiminoglulamic acid and j-forrnirnino-H folate, bear the formimino group —CH hJH. 

A deficiency of folate results in the accumulation of FIGLU, which is excreted in the urine. A histidine load test can be used for detecting folate deficiencies. Patients were given a test dose of histidine (a histidine load), and the amount of FIGLU that appeared in the urine was measured. 

Although the FIGLU test depends on folate nutritional status, the metabolism of histidine wUl 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 Bi2-deficient subjects show increased FIGLU excretion after a histidine load. 

Folate deficiency leads to accumulation of Figlu, which is excreted in urine. The excretion is very pronounced after a loading dose of histidine, a test used to detect folate deficiency. More sensitive radioisotopic assays use folate binders to the vitamins. High urinary levels of Figlu may coexist with elevated levels of serum folate. Thus, in vitamin Bn (cobalamin) deficiency, since cobalamin participates in the following reaction, FH4 is trapped as... 

Increased urinary formiminoglutamic acid in the absence of folic acid deficiency or cobalamine C disease is indicative of formiminotransferase deficiency. Accumulation of imidazolonepropionic acid is not observed, but there is an abnormal excretion of its oxidation product, hydantoin-5-pro-pionic acid. Loading tests with histidine will enhance the excretion. Confirmation of the defect is made by enzyme analysis probably the liver is the only suitable tissue. Affected patients were mentally retarded and/or had convulsions however, a number of healthy siblings with the biochemical abnormality have been described. 

The histidinemic urine is sometimes only weakly positive or negative on ferric chloride testing, which reflects either the instability of imidazole-pyruvic acid, the relation of its excretion to protein intake, immaturity of histidine transaminase, or a combination of these factors. Even after histidine loading, histidinemic neonates excrete much smaller quantities of imi-dazolepyruvic acid than do older children. In patients with urocanase deficiency, the levels of blood histidine and urine imidazolepyruvic acid are normal or slightly elevated. Therefore, it is necessary to do a quantitative analysis of blood histidine and urine ferric chloride test in order to overlook the patients with this condition. 

Abnormal response to a metabolic load, such as the inability to metabolize a test dose of histidine in folate deficiency (Section 10.10.4), or tryptophan in vitamin Be deficiency (Section 9.5.4), although at normal levels of intake there may be no metabolic impairment. 

Bombesin peptide Bombesin was conjugated to JV-acetyl histidine-modified GC for targeting gastric-releasing peptide receptors overexpressed in prostate cancer cells. Iron oxide was loaded to be tested as a probe for MRI [34]... 

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