262 VI. ACETIC. FORMIC, AND PROPIONIC ACIDS 



ordinary fatty acids. Bloch^* reported that leucine and isovaline both 

 yielded acetyl groups to the same degree, thereby indicatmg that isovaline 

 is an mtermediate m leucine catabolism. On the other hand, valine and 

 isobutyric acids, which are non-ketogenic, were likewise found to be 

 ineffective as sources of the acetyl group. 



(3) Acetylation Reactions in the Animal Body 



Acetylation is a process by which the acetyl group is introduced into a 

 molecule. It occurs in the case of many amines before their elimination 

 from the body. It is generally considered to be a method of detoxication, 

 whereby the body tends to modify foreign substances in such a way as to 

 tender them less harmful to the cell. This may be accomplished, either 

 by increasmg their solubility in biologic fluids, thus preventing deposition 

 in the tissues, or by their conversion to substances which have less affinity 

 for enzyme systems. 



However, in some cases, as that of acetylsulfanilamide, the acetylated 

 compound has a greater toxicity, and is more insoluble than is the original 

 product.^" Acetylation, therefore, camiot be considered as a detoxication 

 process,^^'^- but must rather be classed as one of the intermediary reactions 

 in the metabolism of the product under question. Bloch^ is of the opmion 

 that "detoxication" reactions are mediated by enzymes, normally present 

 in the tissues, Avhich catalyze reactions with foreign compounds similar to 

 those observed in normally-occurrmg metabohtes. Thus, the acetylation 

 of a foreign amines is brought about by the enzyme which has as its normal 

 function the acetylation of normally-occurring compounds. 



In addition to the dependence of the degree of acetylation upon dosage,^^ 

 one of the most interesting features of the acetylation reaction is the species 

 difference. For example, rats excrete sulfanilamide partly unchanged, 

 partly as A'-acetylsulfanilamide, and partly in combination with glucuronic 

 acid after the formation of an hydroxyl compound.^ No acetylation of 

 aromatic amines occurs in the ease of dogs or rabbits.^'®* Litchfield"^ 

 studied the excretion of sulfanilamide in several lower verte])rates, and 

 found that it appeared in the urine in a conjugated form in the fish and 

 chicken, but that no conjugated derivative capable of acid hydrolysis was 



«» E. K. Marshall, Jr., W. C. Cutting, and K. Emerson, Jr., /. Am. Med. Assoc, 110, 

 252-257(1938). 



«• J. A. Stekol, Ann. Rev. Biochsm., 10, 265-284 (1941). 



«2 P. Handler and W. A. Perlzweig, Ann. Rev. Biochem., 14, 617-642 (1945). 



" H. G. Bray, F. C. Neale, and W. V. Thort)e, Biochem. J., 40, 406-413 (1946). 



" R. Cohn, Z. physiol. Chem., 17, 274-310 (1893). 



« J. T. Litchfield, J. Pharmacol., 67, 212-223 (1939). 



