ANIMAL METABOLISM ^'^^ 



source of labile methyl groups is one of the essential components of a 

 complete diet for higher animals. However, this requirement can be 

 met indirectly if the diet contains certain vitamins (see below) . 



Methionine itself is also a methyl donor and has been shown to pro- 

 vide methyl groups for the formation of both choline and creatine (p. 

 348) . Choline is produced in the animal body by the addition of methyl 

 groups from methionine to ethanolamine (reaction 46, Fig. 13-6) , which 

 in turn is derived from serine (reaction 45) . Five other substances have 

 now been found which can serve as methyl donors in biological systems. 

 Two of them, betaine [ (CH3)3N+CH2COO-] and dimethyl-propiothetin 

 [(CH3)2S+CH2CH2COO-] occur in nature and probably take .part in 

 methylation reactions in living cells. 



Recent studies have proved that when adequate supplies of folic acid 

 and vitamin B12 are present in the diet, rats can synthesize labile methyl 

 groups from glycine, serine, acetone, or formic acid and hence do not 

 require a methyl donor for growth. This was established by isotopic 

 tracer studies which showed that carbon atoms from these substances 

 appeared in the methyl groups of choline and thymine. Also, when rats 

 were fed a diet containing all the known vitamins including folic acid 

 and vitamin B12, but without any methyl donor, and with homocysteine 

 as the only sulfur-containing amino acid, good growth occurred. Pre- 

 sumably the rats converted the homocysteine into methionine under these 

 conditions. 



Other Metabolic Interconversions oj Amino Acids. As a result of recent 

 investigations, based almost entirely on the use of isotopic tracers, several 

 other metabolic relationships among amino acids have been discovered. 

 For example, L-cystine is synthesized in the animal body from L-serine 

 and L-methionine. The intermediate steps, which involve homocysteine 

 and cystathionine, are shown in Fig. 13-6. In some still obscure manner 

 the cleavage of cystathionine (reaction 41) results in the formation 

 of a-ketobutyric acid as the other product besides cysteine. Note that 

 only the sulfur of the cystine is derived from methionine and that the 

 rest of the molecule comes from serine. 



These reactions provide a reasonable explanation for the fact that 

 cystine is not a nutritionally essential amino acid and that it has a 

 "sparing action" for methionine. That is, when the diet contains plenty 

 of cystine, no methionine has to be diverted to cystine synthesis so that 

 less methionine is needed. Another substance which can give rise to 

 cystine in the body of the rat is L-lanthionine (p. 117). 



Another metabolic relationship, which is now well established, is the 

 formation of serine from glycine. The most probable route of this syn- 

 thesis is shown in Fig. 13-6, reactions 43 and 44. One molecule of glycine 

 is changed into formic acid, which then combines with a second molecule 

 of glycine to form serine. The reverse conversion of serine into glycine 

 also occurs readily in the animal body. 



