Sources of Substituted Folates

The major point of entry for one-carbon fragments into substituted folates is methylene-tetrahydrofolate, which is formed by the catabolism of glycine, serine, and choline. 

---

The major point of entry for one-carbon fragments into substimted folates is methylene tetrahydrofolate (Figure 45-16), which is formed by the reaction of glycine, serine, and choHne with tetrahydrofolate. Serine is the most important source of substituted folates for biosynthetic reactions, and the activity of serine hy-... 

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). 

Figure 45-16. Sources and utilization of one-carbon substituted folates.

Serine Hydroxymethyltransferase Serinehydroxymethyltrans-ferase is a pyridoxed phosphate-dependent aldolase that catalyzes the cleavage of serine to glycine and methylene-tetrahydrofolate (as shown in Figure 10.5). Serine is the major source of one-carbon substituted folates for biosynthetic reactions. At times of increeised cell proliferation, the activities of serine hydroxymethyltransferase emd the enzymes of the serine biosynthetic pathway cue increased. The other product of the reaction, glycine, is also required in increased cimounts under these conditions (for de novo synthesis of purines). 

Disposal of Surplus One-Carbon Fragments With the exception of serine hydroxymethyltransferase (Section 10.3.1.1), till of the reactions shown in Figure 10.4 as sources of one-carbon substituted folates ene essentially catabolic reactions. When there is a greater entry of single carbon units into the folate pool than is required for biosynthetic reactions, the surplus can be oxidized to carbon dioxide byway of 10-formyl-tetrahydrofolate, thus ensuring the availability of tetreihydrofolate for catabolic reactions. 

The metabolic role of folate is as a carrier of one-carbon fragments, both in catabolism and in biosynthetic reactions. As shown in Figure 11.19, these may be carried as formyl, formimino, methyl, methylene or methylene residues. The major sources of these one-carbon fragments and their major uses, as well as the interconversions of the substituted folates, are shown in Figure 11.20. 

Figure 1 1. 20 Sources and utilization of folate derivatives carrying one-carhon fragments and interconversion of the one-carhon substituted folates.

---