46 P-AMINOBENZOIC ACID 



Bray and his associates'" have studied in detail the chemical nature of 

 the metabolites of PABA that occur in the urine of the rabbit. In the light 

 of their experiments it appears that PABA may be excreted by the rabbit 

 in a variety of forms: as free PABA, as the ester-type glucuronide, as the 

 glycine conjugate (PAHA), as acetylated PABA, as acetylated PAHA, and 

 as acetylated glucuronide. Although the various metabolites were not 

 estimated individually, Bray et al. found that only to 21 % of the ad- 

 ministered dose (0.25 to 1.0 g. per kilogram) is excreted as the acetylamino 

 derivatives (acetylated PABA, acetylated PAHA, and acetylated glu- 

 curonide of PABA), whereas 44 to 87% of the dose is excreted as "free 

 diazotizable material" (PABA, PAHA, and glucuronide of PABA). 



These findings render difficult the proper interpretation of any studies 

 on the in vivo acetylation of PABA, either in humans or in lower species, 

 unless such studies have been conducted with reference to the specific 

 form(s) in which the PABA conjugate under investigation has been ex- 

 creted. 



B. EXCRETION IN HUMAN BEINGS 



PABA has been determined in urine by Lewis'-^ with his Lactobacillus 

 arahinosus microbiological method. Normal urine was found to contain 

 about 0.01 to 0.02 y of "free" PABA per milliliter, and about 0.3 to 0.5 y 

 of "combined" PABA per milliliter. When these values are recalculated 

 in terms of probable daily output, about 10 to 20 y of "free" PABA and 

 about 300 to 500 y of "combined" PABA appear to be excreted. 



Landy and Dicken,'- using the Acetohactcr suboxydans assay, found about 

 0.01 to 0.02 7 of "free" PABA per milliliter of normal urine or, on recal- 

 culating to daily output, about 10 to 20 y of "free" PABA per day. 



Thompson el al?^ with the Neurospora crassa p-aminobenzoic-less 

 mutant found 0.02 y of "free" PABA or about 0.5 y of "combined" PABA 

 per milliliter of normal urine. In agreement with Lewis and with Landy 

 and Dicken, this indicates a daily output of about 500 y of "combined" 

 PABA per day. 



PABA excretion in normal adults has been studied by Denko et al.,^^ 

 using the Neurospora crassa p-aminol)enzoic-less assay of Thompson et alP 

 No mention is made in their paper of hydrolysis of samples prior to deter- 

 mination, so it may be presumed that the values reported represent "free" 



2» H. G. Bray, H. S. Lake, F. C. Neale, W. V. Thorpe, and P. B. Wood, Biochem J. 

 42, 434 (1948). 



21 J. C. Lewis, J. Biol. Chem. 146, 441 (1942). 



22 M. Landy and D. M. Dicken, J. Biol. Chem. 146, 109 (1942). 



23 R. C. Thompson, E. R. Isbell, and H. K. Mitchell, /. Biol. Chem. 148, 281 (1943). 



24 C. W. Denko, W. E. Grundy, J. W. Porter, G. H. Berryman, T. E. Friedemann, and 

 J. B. Youmans, Arch. Biochem. 10, 33 (1946). 



