Coenzyme Activity
Folinic acid, citrovorum factor (CF), and leucovorin are names for a naturally occurring derivative offolic acid. Unlike folic acid, this molecule supports the rapid growth of Leuconostoc citrovorum. It has been synthesized and is one of the active coenzyme forms of the vitamin involved in one-carbon (Cl) transfer mechanisms mentioned later. It is N5-formyl-5, 6, 7, 8-tetrahydropteroylglutamic acid (reduced and formylated PGA). The natural material is about twice as active as the synthetic substance, since the latter is a D, L mixture. The L isomer only is utilized by the organisms studied and appears to have the same activity as natural CF. Active enzyme systems have been prepared from liver and kidney which are capable of converting PGA into CF. It is well established that ascorbic acid is involved in this conversion. The administration of ascorbic acid to rats, or to humans given PGA markedly increases the urinary excretion of CF. In monkeys citrovorum factor content of liver was found to be higher with additional ascorbic acid intake but no change in the amount of folic acid ingested:Thus,
Misra and co-workers found that in monkeys on a daily intake of 200 mg of folic acid the CF :tt.ent of liver increased from around 568 to 2375 mug per gram of tissue as the ascorbic d intake was increased from 0 to 50 mg daily. An important, function of ascorbic acid, then, is to maintain folic acid in the reduced form required for coenzyme formation.
It has been proposed that ascorbic acid protects the folic acid reductase and that folic acid ~tagonists, such as aminopterin and amethopterin, inhibit this protection and inactivate the reductase. The different coenzyme forms of folic acid participate in one-carbon metabolism~ number of specific metabolic reactions in which one-carbon units are transferred for the EJllthesis of a variety of molecules. Other coenzyme forms of the vitamin active in Q etabolism are NIO-formyl FH4, N5-10-methylene FH4, N5_ or Nlo-formimino FH4, N5-methyl - F4 and N5-hydroxymethyl FH4'
Among the metabolic reactions discussed under this heading are (1) serineglycine interconversion, (2) purine and pyrimidine synthesis, (3) methionine-homocysteine relations (methyl synthesis), (4.) histidine ~thesis, (5) formiminoglutamate formation, and other one-carbon reactions. Methylation actions in general are discussed under a separate heading.
