8o 



INTERMEDIARY METABOLISM AND GROWTH 



Ornithine to arginine. Both the a- and the s-amino nitrogens of ornithine are in- 

 corporated into tissue arginine in tlie rat (Stetten, 1951). The role of ornithine 

 and arginine in the urea cycle has been recognized for many years. It was 

 noted early that a small amount of ornithine catalyzed the formation of large 

 amounts of urea in liver slices (Ratner, 1955). Gitrulline is an intermediate in this 

 conversion. The ornithine-citrulline-arginine cycle takes place in Neurospora, 

 Penicillium, E. coli, and Tetrahymena as well as in mammalian liver tissue. The 

 first step in arginine synthesis is the formation of citrulline from ornithine. This 

 reaction requires carbamyl phosphate and has been demonstrated in liver and 

 in microorganisms (Fig. 37; Lowenstein and Cohen, 1956; Reichard et al., 1955; 

 Marshall et al., 1955; Jones et al., 1955). The citrulline then reacts with aspartic 

 acid to form an intermediate, argininosuccinic acid. The latter substance is then 

 cleaved by a third enzyme to fumarate and arginine. 



+ H2O 



HN COOH 



(CH2)3 COOH 

 CH-NH. 



CHj-COOH 

 Guanidoacetic 



Arginine 



COOH 

 Fumarate 



Fig. 37. Arginine biosynthesis and the fonnation of creatine. 



Urea, the end product of nitrogen metabolism in the mammal, is formed from 

 arginine as a result of the action of the enzyme, arginase; at the same time, 

 ornithine is regenerated. 



Creatine synthesis and transimidation. Creatine phosphate functions as a storage 

 form of "high-energy phosphate bonds" in mammalian tissues. Guanidoacetic 

 acid the intermediate in creatine synthesis is formed by a condensation of the 

 guanido group of arginine with glycine. This is followed by the methylation of 

 guanidoacetic acid to creatine by the transfer of a methyl group from methionine 

 (Fig. 37) . The amidine group of arginine ( = N — C = N — ) is transferred as a unit 

 (Stetten and Bloom, 1956) during guanidoacetate synthesis. The reaction is 

 reversible; labelled arginine can be formed from guanidoacetic acid labelled 



