84 INTERMEDIARY METABOLISM AND GROWTH I 



synthesis of amino acids from keto acids must take place (Meister, 1954). Isotope 

 competition experiments (Abelson, 1954) are consistent with the possibiUty that in 

 E. coll, isoleucine, leucine, valine, alanine, glutamic, aspartic, and phenylalanine 

 are formed from their keto acids. The transfer of the nitrogen atom of amino acids in 

 animal tissues was demonstrated by Schoenheimer and associates: the '^N of dietary 

 leucine or glycine was rapidly transferred to almost all of the amino acids of the 

 tissue protein except threonine and lysine (Schoenheimer, 1942). 



In 1930, Needham demonstrated that muscle "brei" catalyzed the anaerobic 

 disappearance of gkitamic acid without formation of free NH3. When it was found 

 that aspartic acid and a-ketoglutarate were products of this reaction, it became 

 apparent that amino acids were in many cases synthesized from keto acids by 

 transamination : 



pyridoxal-P 

 i) Glutamic + oxalacetic -< t a-ketoglutaric + aspartic 



Pyridoxal phosphate and pyridoxamine are cofactors in transamination reactions 

 (Meister, 1954, 1955). It is probable that the amino group is transferred from 

 amino acids to pyridoxal phosphate and that the pyridoxamine phosphate which 

 is thereby formed, next transfers the amino group to a keto acid, thereby regener- 

 ating the pyridoxal phosphate. The transfer of '^N from pyridoxamine-phos- 

 phate and from amino acids to a-ketoglutarate has been demonstrated in pig heart 

 homogenates (Tanenbaum, 1956). 



The activity of transaminase enzymes varies with the amino and keto acid 

 substrates. The most active transaminases of the cell are those which catalyze 

 reaction i) and reaction 2): 



2) Glutamic + pyruvate ■" ^ a-ketoglutaric + alanine 



Less active transamination reactions can be demonstrated in most tissues for the 

 following substrates: 



3) i Leucine + a-ketoglutarate ■' — ' glutamic + a-ketoisocaproate j 

 ■ Isoleucine a-keto-[3-methylvalerate 



' Valine a-ketoisovalerate ] 



The close relationship between alanine and the dicarboxylic amino acids and the 

 glycolytic and tricarboxylic acid cycles should be noted. 



Transamination reactions involving other pairs of amino acids and keto acids 

 have also been found. a-Ketoglutarate functions as an amino acceptor in 

 transamination reactions with practically all of the amino acids. Reactions are 

 also known in which monoamino monocarboxylic acids and a-keto monocarbo- 

 xylic acids are the substrates and products: 



4) ) Pyruvate + valine < — r a-ketoisovalerate + alanine | 

 I a-Ketobutyrate a-aminobutyrate ( 



Reactions between glutamic acid and the aldehydes, glyoxylate, glutamic 

 semialdehyde, and succinic semialdehyde also occur. There is an interesting reac- 

 tion between ornithine and glyoxylate, in which aldehydes are substrates and 

 products of the reaction: 



