Figlu

For correlation with the serum folic acid, FIGlu determinations were carried out using two methods (L9, S6). Both proved insensitive, notably where no urinary FIGlu was excreted despite clinical proof of PGA deficiency. 

Fig. 3.2.3 Profiles of acylcarnitines as their butyl esters in plasma (precursor of m/z 85 scan) of a normal control (a) and three patients with elevated Gi-acyl carnitine (m/z 288 peak 4) that represents primarily butyrylcarnitine in a patient with short-chain acyl-CoA dehydrogenase (SCAD) deficiency (b), isobutyrylcarnitine in a patient with isobutyryl-CoA dehydrogenase (IBDH) deficiency (c), and a natural isotope of formiminoglutamate (FIGLU m/z 287 peak 3) in a patient with glutamate formimino-transferase deficiency (d). Peak 1 free carnitine (m/z 218), peak 2 acetylcarnitine (C2 m/z 260). The asterisks represent the internal standards (from left to right) d3-acetylcarnitine (C2 m/z 263), d3-propionylcarnitine (C3 m/z 277), d3-butyrylcarnitine (C4 m/z 291), d3-octanoylcarnitine (C8 m/z 347), d3-dodecanoylcarnitine (Ci, m/z 403), and d3-pal-mitoylcarnitine (Ci6 m/z 459)...

Formiminoglutamate (FIGLU), a marker for glutamate formimino-transferase deficiency, was recently also shown to be detectable by acylcarnitine analysis represented as a peak with m/z 287 (Fig. 3.2.3d) [64]. In poorly resolved acylcarnitine profiles, this peak may be confused with iso-/butyrylcarnitine (m/z 288). To avoid the incorrect interpretation of acylcarnitine profiles, we recommend performing the analysis in product scan mode as opposed to multiple reaction monitoring (MRM) mode. For example, the FIGLU peak at m/z 287 would not have been correctly identified in MRM mode because the transition of 287 to 85 is typically not selected. However, the 288/85 transition would reveal abnormal results, but in fact not represent either butyryl- or isobutyrylcarnitine, but another FIGLU related ion species. 

Fig. 11.6. Interconversions of tetrahydrofolate derivatives. FH2 = dihydrofolic acid FH4 = tetrahydrofolic acid AICAR -= 5 aminoimidazole 4-carboxamide ribonucleotide FAICAR = formyl AICAR GAR = glycinamide ribonucleotide FGAR = formyl GAR Glu = glutamic acid FIGLU = formimino glutamic acid. (Modified from Mudd and Cantoni, 1964.)...

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

Figure 10.6. Catabolism of histidine - basis of the FIGLU test for folate status. Histidase, EC 4.3.1.3 urocanase, EC 4.2.1.49 FIGLU formiminotransferase, EC 2.1.2.5. THF, tetrahydrofolate.

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,... 

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 stams. In folate deficiency, the activity of the formimi-notransferase 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). 

Formylglutamate can transfer its formyl group directly onto tetrahydrofolate to yield 5-formyl-tetrahydrofolate. Formyl-glutamate is not a normal physiological intermediate, and the formation of 5-formyl-tetrahydrofolate is probably a side reaction of FIGLU formiminotransferase. 

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. 

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. 

CataboUsm of histidine - basis of the FIGLU test for folate status. 282... 

Transcorrin II bound vitamin B12 Mean cell volume Serum methylmalonic acid Serum homocysteine Urine FIGLU more than 8 h after histidine load — <0.15 <0.22 >100 fL >1 i.mol/L >20 i.mol/L >50 [ig /mL ... 

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

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