PANTOTHEMIC ACID 341 



Although the folic acid molecule contains the structure of p-amino- 

 benzoic acid, it seems doubtful that the major function of PABA is in 

 the formation of folic acid; for example, folic acid does not replace 

 PABA for Neurospora crassa (1, 333). Several metabolic roles of PABA 

 have been suggested, especially a function in the introduction of 1 -car- 

 bon intermediates into other compounds (254). The fact that methio- 

 nine replaces PABA for a mutant of Neurospora crassa supports this 

 possibility; the vitamin here probably functions in the methylation of 

 homocysteine (269). Other functions no doubt exist (266), but they 

 have not yet been shown in the fungi. 



The biosynthesis of PABA by Neurospora crassa is a special case of 

 aromatic synthesis. A single gene mutant is deficient for PABA, trypto- 

 phan, phenylalanine, and tyrosine; shikimic acid replaces all these re- 

 quirements (280). The probable pathway of the synthesis is consid- 

 ered elsewhere (Chapter 8). 



PABA in high concentrations is toxic to fungi (38), but in Neuro- 

 spora crassa it is converted to a pigment of unknown structure and to 

 N-acetyl-p-aminobenzoic acid (200). The acetylation of PABA occurs 

 also in animal tissues (323). 



The metabolic importance of PABA was first recognized by Woods 

 (307), who found that the bacteriostatic effect of sulfanilamide is com- 

 petitively antagonized by PABA. The same antagonism has been ob- 

 served in fungi (24, 48, 99), and we may assume that the same mech- 

 anism prevails. 



Emerson and Cushing (58) isolated a sulfonamide-resistant mutant 

 of Neurospora crassa and a second mutant requiring sulfonamides for 

 growth. The requirement is absolute at 35 °C, partial at lower incuba- 

 tion temperatures (56). Later studies by Zalokar (333) suggest that the 

 sulfa-requiring strain is abnormally sensitive to the PABA which is 

 formed in its own cells; the beneficial effect of sulfonamides is, in this 

 view, based on its antagonism of the toxic effect of PABA. Some of 

 the difficulties of this hypothesis are discussed by Mitchell (171); a rela- 

 tionship to amino acid metabolism is apparently involved (57, 334). 

 The present uncertain status of the sulfonamide requirement reflects 

 the limitations of growth methods used by themselves for the solution 

 of essentially biochemical problems. 



12. PANTOTHENIC ACID 



Requirements for pantothenic acid, although fairly common in 

 yeasts (27, 29, 134), are rare or unknown in the filamentous fungi. 

 Penicillium digitatum is stimulated in the early stages of growth by 



