Folate metabolism turnover

Gregory JF, III, Williamson J, Liao JF, Bailey LB, Toth JR Kinetic model of folate metabolism in nonpregnant women consuming [2H2]folic acid isotopic labeling of urinary folate and the catabolite para-acetamidobenzoylglutamate indicates slow, intake-dependent, turnover of folate pools. J Nutr 1998 128 1896-906. 

FIG. 3. Two-pool model of folate metabolism with output only from the rapid turnover pool. Output represents the sum of urinary, fecal, and catabolic losses. 

FIG. 6. Expanded model of in vivo folate metabolism. Tbe pools are defined as follows 1, rapid turnover folate 6, slow turnover folate (tissues) 2, irretrievable losses by fecal excretion and catabolism 3, cumulative excretion of urinary folate 4, fractional (daily) excretion of urinary folate. Analysis was performed with parallel models for labeled and nonlabeled folate. 

The lack of hard evidence about the extent of supplementation required in pregnancy prompted the development of a laboratory-based assessment of metabolic turnover, which involved the assay of total daily folate catabolites (along with intact folate) in the urine of pregnant women. The rationale of the procedure was that this catabolic product represents an ineluctable daily loss of folate, the replacement of which should constitute the daily requirement. Correcting for individual variation in catabolite excretion and the bioavailability of dietary folate, the recommended allowances based on this mode of assessment are in close agreement with the latest recommendations of the USA/Canada and FAO/WHO. The data produced by the catabolite-excretion method may provide a useful adjunct to current methods... 

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metabolism of certain amino acids. Fohc acid deficiency results in an inability to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metabolic requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red andpainfiil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

Many patients with infection have a reduced serum level of folate, particularly those with chronic bacterial infections. However, the development of a megaloblastic anemia is uncommon and when it does occur is perhaps more often associated with the treatment. It is probable that the folate deficiency is the result of a combination of fiictors including poor dietary intake, low reserves, an increased demand due to an increased cell turnover, impaired absorption, vomiting, and impaired metabolism due to the toxic state of the patient (C17, M16, W25). Pyrexia may also inhibit the reduction of folate. Panders and Rupert (P13) found that if folic acid was incubated with a chicken liver enzyme preparation at an elevated temperature the reduction of folic acid to tetrahydrofolic acid was inhibited. 

The use of animal models will be of help in this area as various tissues may be sampled over time to determine folate stores and turnover. This information can then be extrapolated to a human kinetic model based on known similarities and differences in metabolism between the species. 

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