44 P-AMINOBENZOIC ACID 



The distribution of PABA in the tissues of rats 2 hours after the oral 

 administration of the sodium salt at a level of 5 g. per kilogram of body 

 weight was studied by Tabor et at} Free amine is found in greatest con- 

 centration in lung, liver, and kidney {ca. 1.3 mg. per gram), and in a lower 

 concentration in brain and muscle {ca. 0.4 mg. per gram). The per cent 

 conjugated is low and probably insignificant. The concentration in plasma 

 (1.35 mg. per gram) is twice that in red blood cells. 



The acetylation of PABA as a method of "detoxification" prior to elimin- 

 ation in the urine appears to have been observed first in the rabbit by 

 Ellinger and HenseP and subsequently in man by Muenzen ct al* 



Increased amounts of acetylated PABA were found by Harrow et al} 

 to occur in the urine of rabbits as a result of insulin injections. The same 

 group observed that acetylation of PABA by the rabbit is increased by 

 the simultaneous administration of a variety of compounds that presum- 

 ably function as a source of acetyl donors.^"'' 



Increased acetylation of PABA (0.2 g. per kilogram per os) was observed 

 in rabbits by Venkataraman et al}^ when glycine or DL-malic acid was fed 

 along with the compound. The excretion of PABA as the glucuronide was 

 also observed. When excretion of acetylated PABA was increased by the 

 simultaneous administration of glycine or DL-malic acid, there was a de- 

 crease in that portion of PABA excreted in the acetylated form. Chara- 

 lampous and Hegsted" point out that the administration of PABA in 

 large amounts imposes a stress on the animal, so that increases in acetyla- 

 tion thus observed represent a measure of the effectiveness of such com- 

 pounds as acetyl donors. 



Acetylation of PABA is impaired in the rat made diabetic with alloxan." 

 Acetylation in such animals is normal again after the administration of 

 insulin, dicarboxylic acids of the tricarboxylic acid cycle, ATP, acetyl 

 phosphate, or diacetyl. A return to normal is seen in the fasting animal as 

 well as in animals on a high fat diet. Such an effect is not apparent, how- 

 ever, when acetate, acetylmethyl acetate, pyruvate, lactate, glycerol 

 diacetate, acetoin, butylene glycol, phosphate salt, adenylic acid, or panto- 



3 A. Ellinger and M. Hensel, Z. phrjsiol. Chem. 91, 21 (1914). 



^ J. B. Muenzen, L. R. Cerecedo, and C. P. Sherwin, /. Biol. Client. 67, 469 (1926). 

 5 B. Harrow, A. Mazur, and C. P. Sherwin, J. Biol. Chem. 102, 35 (1933). 

 ^ B. Harrow, A. Mazur, E. Borek, and C. P. Sherwin, ,/. Biol. Chem. 105, xxxiv 

 (1934). 



7 B. Harrow, A. Mazur, E. Borek, and C. P. Slierwin, Biochcm. Z. 293, 302 (1937). 



8 E. A. Doisy, Jr., and W. W. Westerfeld, J. Biol. Chem. 149, 229 (1943). 



9 B. Harrow, F. W. Power, and C. P. Sherwin, Proc. Soc. Exptl. Biol. Med. 24, 

 422 (1927). 



'" P. R. Venkataraman, .V. Venkataraman, and H. B. Lewis, .\rch. Biocheiii. 26, 



173 (1950). 

 " F. C. Charalampous and 1). M. Hegstcd, J. Biol. Chem. 180, 623 (1949). 



