Formimino-transferase

This enzyme designation was formerly classified as EC 2.1.2.6. It is now classified under glutamate formimino-transferase [EC 2.1.2.5]. 

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. 

FIGURE 18-26 Catabolic pathways for arginine, histidine, glutamate, glutamine, and proline. These amino acids are converted to a-ketoglutarate. The numbered steps in the histidine pathway are catalyzed by histidine ammonia lyase, urocanate hydratase, imida-zolonepropionase, and glutamate formimino transferase. 

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). 

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 formimino transferase. 

Methionine synthase 7,8-Dihydrofolate reductase Serine hydroxymethyl transferase Glutamate formimino transferase Formimino-THF-cyclodesaminase 10-Formyl-THF synthetase... 

Formimino- transferase deficiency Formiminotransferase Liver 21q223 229100... 

Formimino transferase is readily assayed by the ultraviolet absorption peak 267) at 355 my at pH 7 of 5,10-methenyl-FH4. The enzsrme was purified from acetone powder extracts of hog liver a 700-fold purification was achieved with (NH4) 04 and isoelectric precipitation. This, however, did not free the transferase enzyme from the next enzyme, formimino-FH4 cyclodeaminase. This was accomplished by treatment with chymotrypsin, which preferentially inactivated the latter. 

When formiminoglycine (FIG) was broken down to glycine, derivatives of folic acid were involved and ATP formation occurred (H, 297). These reactions are shown in Fig. 17. The first of these reactions was catalyzed by FIG formimino transferase FIG reacted with FH4, free glycine was formed, and iV -formimino-FH now carried the formimino grouping. In the second step, NH3 was released from iNT -formimino-FEU and the cyclic iVs. Vio-imidazolinium derivative of iV -formyl-FH4 resulted. The latter compound was also called lV ,Ari >-methenyl-FH4, anhydroleucovorin, or anhydrocitrovorum factor the enzyme responsible for the formation of the imidazolinium derivative from A -formimino-FH4 was named formimino-FH4 cyclodeaminase. In the third reaction, methenyl-FH4 cyclohydrolase catalyzed the conversion of lV ,iW -methenyl-FH4 to JV -formyl-FH4. The fourth step, which resulted in ATP formation, was catalyzed by FH4-formylase. ADP and P reacted with JW -formyl-FH4 and produced FH4, free formic acid, and ATP. The reverse of this reaction resulted in the activation of free formic acid [Eq. (5)]. 

FIQLU + 6-CHNH—FH. -1-glutamic acid Formimino transferase (from liver) (41,58)... 

Fig. 18. AC profile from a case of glutamate formimino-transferase deficiency. Ion at 288 Th is not due to C4-camitine but it is just the C13 isotopomer of FIGLU with main ion at 287 Th.

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