120 



INTERMEDIARY METABOLISM AND GROWTH 



Leucovorin 

 Folinic 



Ln.Citrovorum Factor 

 N^-Formyl-THFA 



GAR 



A I CAR 



■ FGAR 

 -IMP 



sulfanilamide 



|N^°-Formyl-THFAU 

 |N^°-Hydroxymethyl-THFA| UDr 



CDr 



2 TPNH2\ 



Folic 



Pteroylglutamic (PGA) 



Lb. easel Factor 



Homocysteine 



Ethanolamine 



a - Ketoisovalerate 



MeCDr 



Thymidine 



■ Methionine 



• Choline 



• Ketopantoate 



Fig. 59. Scheme showing possible metaboUc relationship between /;-aniinobenzoic acid 

 and some members of the folic acid group. 



mutants manifest a multiple requirement for PABA, j&-hydroxybenzoic acid, 

 tyrosine, phenylalanine, tryptophane, and under certain conditions, a sixth factor 

 (Davis, 1955a, b). The synthesis of aromatic compounds via shikimic acid has 

 been discussed in connection with tyrosine synthesis. The synthesis of folic acid 

 from glutamic acid, PABA, and glucose, has been demonstrated using Lb. plan- 

 tarum 56" and Ln. mesenteroides P-60 (Woods, 1954). No preformed pteridine needs 

 to be added to growing cultures of these bacteria to effect folic acid synthesis. 

 Sulfonamide compounds inhibit this synthesis by competition with PABA. 



Folic acid can replace PABA as a growth factor and it can non-competitively overcome 

 the inhibition of bacterial growth due to the sulfonamides in some microorganisms. 

 However, for others, folic acid is either inactive or is less active than PABA itself. 

 Likewise, folinic is not appreciably more active than folic acid as a substitute for PABA 

 except for Ln. mesenteroides P-60. This latter organism grows equally well on PABA or 

 folinic but not at all on folic acid. These facts cast doubt on the concept that folic 

 acid and folinic acid are direct intermediates in the synthesis of the folic acid coenzyme. 

 Similarly, pteroic acid and its N>o-formyl derivative, rhizopterin are probably not direct 

 products of PABA utilization. These substances are inactive or are competitive rather than 

 non-competitive in overcoming sulfonamide inhibition with Lb. plantariim and other 

 organisms for which folic acid is effective in rendering the organism insensitive to the drug. 

 p-Aminobenzoylglutamate, another possible intermediate in the synthesis of the folic acid 

 coenzyme, in the few cases where it is active, always shows a competitive relation with 

 the sulfonamides. 



Certain strains of bacteria are unable to synthesize folic acid derivatives from PABA. 

 Thus, Lb. casei requires folic acid or folinic as a growth factor, Ln. citrovorum grows on 

 folinic acid but not folic acid, while S.faecalis R requires rhizopterin. 



Tetrahydro derivatives of folic acid or pteroic acid or polyglutamate derivatives 

 may be the direct intermediates in the synthesis of the coenzyme. N^^-formyl tetra- 

 hydrofolic acid has been implicated in the formation of inosinic acid (Jaenicke, 

 1955; Greenberg et al., 1955). Folinic acid is active to the degree that it can be 



