Citrovorum factor Leucovorin, Folinic

Cltrivorum factor (CF), folinic acid, and leuco-vorin are all N-[4[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]-amino]benzoyl]glutamic acid, I, the Leuconostoc citrovorum 8081 growth factor first reported by Sauberlich and Baumann.1 Leucovorin refers to the chemically synthesized material that contains both dL and 1L diastereomers "citrovorum factor" and "folinic acid" generally apply to the biologically synthesized 1L isomer. 

Johnson and colleagues made a provocative observation in the course of exploratory preclinical toxicological studies of vincristine, namely, that folinic acid (Leucovorin citrovorum factor 5-formyl-5,6,7,8-tetrahy-drofolic acid) was able to protect mice from the toxicity of high doses of vincristine lb). Vincristine, at a dose of 2.5 mg/kg administered intravenously, resulted in a mortality of 90% over a period of 30 days, but treatment with folinic acid lowered the mortality to 25%. The protection against vincristine toxicity did not occur when folic acid was substituted for folinic acid. A report has appeared (45) indicating that there is no specific protective effect of folinic acid against vincristine toxicity in mice and that the protection can be observed by comparable treatment with isotonic saline solution. As discussed in Section Vll, there is not conclusive evidence that folinic acid is able to ameliorate vincristine toxicity in humans (46). 

Leucovorin Calcium (Folinic Acid Citrovorum Factor)... 

Inhibition of nudeobase synthesis (2). Tet-rahydrofolic acid (THF) is required for the synthesis of both purine bases and thymidine. Formation of THF from folic acid involves dihydrofolate reductase (p. 274). The folate analogues aminopterin and methotrexate (amethopterin) inhibit enzyme activity. Cellular stores of THF are depleted. The effect of these antimetabolites can be reversed by administration of folinic acid (5-formyl-THF, leucovorin, citrovorum factor). Hydroxyurea (hydroxycarbamide) inhibits ribonucleotide reductase that normally converts ribonucleotides into deoxyribonucleotides subsequently used as DNA building blocks. 

There are several one-carbon derivatives of folate (of different redox states) that function as one-carbon carriers in different metabolic processes. In all of these reactions, the one-carbon moiety is carried in a covalent linkage to one or both of the nitrogen atoms at the 5- and 10-positions of the pteroic acid portion of tetrahydrofolate. Six known forms of carrier are shown in Figure 27-4. Folinic acid (N -formyl FH4), also called leucovorin or citrovorum factor, is chemically stable and is used clinically to prevent or reverse the toxic effect of folate antimetabolites, such as methotrexate and pyrimethamine. The formation and interconversion of some metabolites of... 

Antifolate chemotherapy produced the first cure of a solid tumor, choriocarcinoma. Introduction of high-dose regimens with rescue of host toxicity by the reduced folate, leucovorin (folinic acid, citrovorum factor, 5-formyl tetrahydrofolate, N -formyl FH ), further extended the effectiveness of these drugs to both systemic and CNS lymphomas, osteogenic sarcoma, and leukemias. Most recently, analogs that differ from methotrexate in their transport properties and sites of action have proven useful in treating other cancers. 

Formyl H4-folate (folinic acid, leucovorin, citrovorum factor)... 

The Citrovorum Factor is a growth factor for Leuconoatoc citro-vorum. It may be the active form of folic acid. Synthetic citrovorum factor (folinic acid, leucovorin) is formyl tetrahydrofolic acid. Conversion of pteroylglutamic acid to the citrovorum factor is believed to be helped in vitro and in vivo by ascorbic acid (see pages 186 and 188). 

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