Formiminoglutamic

B37. Brown, D. D., Silva, O. L., Gardiner, R. C., and Silverman, M., Metabolism of formiminoglutamic acid by vitamin B12 and folic acid deficient rats fed excess methionine. J. Biol. Chem. 235, 2058-2062 (1960). 

K7. Kohn, J., Mollin, D. L., and Rosenbach, L. M., Conventional voltage electrophoresis for formiminoglutamic acid determination and folic acid deficiency. /. Clin. Pathol. 14, 345-350 (1961). 

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. 

Catabolism of histidine. The first steps of the major degradative pathway for histidine metabolism have already been discussed. Elimination of ammonia, followed by hydration and ring cleavage to formiminoglutamate, involves unusual reactions (Eq. 25-14)252 which have been discussed earlier. Transfer of the formimino group to tetrahydrofolic acid and its further metabolism have also been considered (Chapter 15). 

Figure 20.25 Catabolism of histidine. A and B indicate lesions in histidinemia and formiminoglutamic aciduria, respectively.

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

Experimental animals that have been exposed to ititrous oxide to deplete vitamin B12 show an increase in the proportion of liver folate present as methyl-tetrahydrofolate (85% rather than the normal 45%), largely at the expense of unsubstituted tetrahydrofolate and increased urinary loss of methyl-tetrahydrofolate (Horne et al., 1989). Tissue retention of folate is impaired because methyl-tetrahydrofolate is a poor substrate for polyglutamyl-folate synthetase, compared with unsubstituted tetrahydrofolate (Section 10.2.2.1). As a result of this, vitamin B12 deficiency is frequently accompanied by biochemical evidence of functional folate deficiency, including impaired metabolism of histidine (excretion of formiminoglutamate Section 10.3.1.2) and impaired thymidylate synthetase activity (as shown by abnormally low dUMP suppression Section 10.3.3.3), although plasma concentrations of methyl-tetrahydrofolate are normal or elevated. 

Chanarin, L, Rothman, D and Watson-Williams, E, J, (1963). Normal formiminoglutamic acid excretion in megaloblastic anemia In pregnancy. Lancet 1,1068-1072. 

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 shown (Figures 9.16 and 9.17). The intermediates, formiminoglutamic acid and 5-formimino-H4folate, bear the formimino group —CH=NH. 

Connecting peptide of insulin Cytosine triphosphate Extracellular fluid Essential fatty acid Endoplasmic reticulum Fructose-l,6-bisphosphate Flavin adenine dinucleotide Free fatty acid Formiminoglutamic acid Glucose transporter gene or protein... 

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