Mechanisms of folate homeostasis.

Recent work has provided information that allows the delineation of the mechanisms by which folate homeostasis is maintained. Dietary folates are converted to monoglutamates in the gut, absorbed by an active process, and distributed to tissues by the enterohepatic cycle, possibly utilizing folic acid binding proteins. During short periods of dietary deprivation, supply is maintained in the monoglutamate pools in the enterohepatic cycle as well as within cells. A net increase in available folate results from a decrease in tissue uptake and in subsequent polyglutamate synthesis, coupled with a fixed rate of conversion of polyglutamate to monoglutamate and release from the cell. The liver exerts substantial regulatory effect because of its mass, relatively rapid folate turnover, and the large folate flux through the enterohepatic cycle. In addition, there is a substantial, if more long-term, contribution from tissues that die and release folates (e.g., red blood cells), and a pathway exists that is capable of salvaging this folate and returning it to the liver for subsequent redistribution to actively proliferating cells.