10-Formyltetrahydrofolic acid 10-formyl

FoNiiic add /V-[(65)-5-formyl-5,6,7,8-tetrahydropte-royl]-L-glutamic acid, (6S)-5-formyltetrahydrofolic acid, leucovorin. ... 

FoUnic acid can be formed along with A i -formyltetrahydrofolic acid by direct formylation of 5,6,7,8-tetrahydrofolic acid. Both tetra- and di-hydro-... 

It is of interest that many of the reduced folic derivatives prepared as a result of chemical studies of growth factors have subsequently been foimd to serve directly as coenzymes in the transfer of single carbon units. Reversible enzymatic transfer of the single carbon unit from anhydrofolinic acid to glycineamide ribotide, from Ai -formyltetrahydrofolic acid to 5-amino-4-imidazolecarboxamide ribotide, and from folinic acid to glutamic acid have been observed to be specific for these respective formyl donors -. ... 

The formylation of GAR to produce FGAR is catalyzed by glycinamide ribonucleotide transformylase. The immediate formyl donors are derivatives of tetrahydrofolic acid (FIR) (96, 107, 108). With purified enzyme preparations, iV, Ar -anhydroformyltetrahydrofolic acid alone donates its formyl group to GAR (/09). Because of their rapid interconversion by the enzyme cyclohydrolase (110), both JV -formyltetrahydrofolic acid and W, Ar -arjhydroformyltetrahydrofolio acid were reactive in crude enzyme... 

The reaction of a one-carbon compound with 5-amino-4-imidazolecar-boxamide ribonucleotide (AICAR) (Fig. 3) completed the purine ring and resulted in the formation of inosinic acid (IMP). AICAR had been postulated earlier as an intermediate in purine syntheris and a stimulatory effect of JV -formyltetrahydrofolic acid (JV -formyl-FH4) on the entry on the one-carbon unit was observed (68). Also, glycine accepted the one-carbon unit from position 2 of IMP, which resulted in the formation of serine and AICAR (143). The reaction was reversible, since AICAR was converted to IMP in the presence of serine (144)- The reaction of AICAR with serine required-TPN and K" ", in addition to a folic acid compound (either Ar5,ATio.anhydroformyl-FH4 or iV -anhydroformyl-FH4) (143). The equation for the reaction is ... 

SCHEME 22.4 Hydrogenation of folic acid and fnrther formylation to 5-formyltetrahydrofolic acid. 

Enzyme synthesis in vitro depends on the presence of N-formyl-methionine tRNA et. However, in systems prepared from normal cells there is no requirement for a formyl donor, since the cells contain an excess of the formyl donor N -formyltetrahydrofolic acid, stuck primarily to the ribosomes after disruption. Similar to the case with other tRNA species, the requirement for formylmethionyl can only be detected after special treatment of... 

The interconversion of these forms of foiic acid takes place through various electron transfer reactions facilitated by specific enzyme systems and coenzymes, such as the reduced forms of fiavin-adenine dinucleotide (FADH2) and NADPH. The conversion between the N -, N -methylene form and -formyl forms is readily reversible, but the reduction of methylene to methyl and reduction of free THF to formyltetrahydrofolate is essentially irreversible. Conversion of N -methyltetrahydrofolate back to free THF. may require cobalamin. 

After folic acid is converted to N °-formyltetrahydrofolate, it acts as a carrier of formyl groups and is a substrate for a transformylase reaction that converts Met-tRNAf to fMet-tRNA(—the initiator tRNA. (See p. 828 in the text.)... 

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