Histidine, catabolism

Although catabolism of histidine is not a major source of substituted folate, the reaction is of interest because it has been exploited as a means of assessing folate nutritional status. In folate deficiency, the activity of the formimino transferase is impaired by lack of cofactor. After a loading dose of histidine, there is impaired oxidative metabolism of histidine and accumulation of FIGLU, which is excreted in the urine (Section 10.10.4). 

A single bifunctional enzyme catalyzes the FIGLU formiminotransferase and formiminofolate cyclodeaminase reactions, so there is little or no free formimino-tetrahydrofolate in tissues under normal conditions. The two catalytic sites are separate, and with tetrahydrofolate monoglutamate, there is release of the formimino derivative. However, when polyglutamates are used, 

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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. 

The histidine catabolic pathway is discussed under Folate in Chapter 9. The material reveals that histidine is catabolized to produce glutamate. Glutamate in turn, can be converted to a-ketoglutarate and completely oxidized to CO in the Krebs cycle. In the study depicted in Figure 8,26, the dietary histidine was spiked with I Cjhistidine, The term "spiked" means that only a very small proportion of the histidine contained carbon-14. The metabolic behavior of the radioactive histidine, which can be followed, mirrors the metabolic fate of nonradioactive histidine in the diet. All of the CQz exhaled by the rats can be easily collected, The " COj present in the rat s breath can be measured by use of a liquid scintillation counter. The amount of CO2 produced directly mirrors the proportion of histidine, absorbed from the diet that was degraded the rat s body. 

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. 

FEGURB 916 Simplified diagram of histidine eaiabolism. FIGLU is an iDtennedlate in the pathway of histidine catabolism that may appear in elevated amounts Ln the urine during folate dcficicnqi. ... 

Histidine Catabolism As shown in Figure 10.6, the catabolism of histidine leads to the formation of formiminoglutamate (FIGLU). The... 

Serum/giyeine metaboUsm Histidine catabolism Thymidylate synthesis Melhibnine synthesis Purine isyhthesis... 

Folic acid also has an important role in histidine catabolism (Fig. 4), where the formimino group of the end-stage product formiminoglutamic acid is transferred to tetrahydrofolate, giving formiminotetrahydrofolate. 

Histidine catabolism. The major pathway of histidine catabolism to form ammonia and... 

The main source of C, units is the hydroxymethyl group of serine, which is transferred to THF by serine hydroxymethyltransferase (EC 2.1.2.1), forming fV -hydroxymethyl-THF (activated form dehyde). Production of C, units during histidine catabolism and in the anaerobic degradation of purines is of particular importance. C, units are incorporated during purine biosynthesis, and they provide the S-methyl group of thymine. C units are interconverted while attached to THF (Hg.2). For other metabolic sources and uses of C units, see legend to Fig.2. 

Fig. 5.1. Pathways of histidine catabolism, including possible metabolic defects. 5.1, His-tidase (histidine ammonia-lyase) 5.2, urocanase 5.3, formiminotransferase. THF, tetra-hydrofolic acid. Pathological metabolites used as specific markers in the differential diagnosis are marked in squares...

Let s say that you want to study one of the more complex and interesting amino acid catabolic pathways and that you need to view urocanase, a key enzyme in histidine catabolism that catalyzes the addition of water to trans-urocanate. 

Histidine catabolism begins with elimination of ammonia to give trans-... 

Study of the enzymic reactions of histidine catabolism was aided tremendously by the observation that urocanic acid exhibits a strong absorption in the ultraviolet region with a maximum at 277 m/u and a molar extinction coefficient of 18,000 (S4S, XS6). This property renders it very convraiient to follow both the formation of urocanic acid from histidine and its disappearance spectrophotometrically. The observation that in the enzymic decomposition of urocanic acid a product with an absorption peak at 264 m i is formed also is of extreme importance in following the further sequence of the reactions of histidine catabolism 257, 258). 

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