CASE FILES: BIOCHEMISTRY
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.