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CASE FILES: BIOCHEMISTRY

Figure 4-3.

Reaction pathways showing the interconversion of 1-carbon carri-

ers of tetrahydrofolate (THF). Note that all interconversions are reversible

except for the conversion of N5,N10-methylene THF to N5-methyl THF.

Folate deficiency perturbs DNA metabolism and methylation reactions.

Leafy green vegetables are good sources of folate;

however, folate is labile

and may be damaged during food preparation. Another dietary source of folate

is cereal products, especially breads and breakfast cereals that have been forti-

fied with folic acid. Folate is also produced within the gut lumen by certain

intestinal bacteria; however, the amount of folate absorbed from this source

is minor in humans. In its simplest form, folate consists of three connected

chemical moieties: a pteridine ring (6-methylpterin), p-aminobenzoic acid

(PABA), and glutamate. In nature, folate is generally polyglutamated (deco-

rated by two to seven additional glutamic acid residues). Conjugases (y-glutamyl

carboxypeptidases) in the intestinal lumen cleave off extra glutamic acid

residues, and folate is absorbed by the mucosa of the small intestine (Figure 4-4).

In cases of chronic alcoholism, folate deficiency may result from poor nutri-

tion or from poor absorption of folate secondary to a conjugase deficiency.

Once folate deficiency occurs, abnormal megaloblastic replication of epithe-

lial mucosa can occur, which further impairs folate uptake.

After absorption, folate is reduced to THF by dihydrofolate reductase. The

majority of circulating folate is in the form of N5-methyl THF. Cells use spe-

cific transporters for THF uptake, and cellular machinery polyglutamates the

folate to aid in cellular retention.