PROTEIN METABOLISM 771 



of this acid to the total nitrogen indicates that the whole of the tyrosine and 

 phenylalanine of the protein molecule, whether set free in the alimentary 

 canal or in the tissue metabolism, is converted into homogentisic acid. It 

 is not possible to conceive of the direct conversion of 



/x 



tyrosine into homogentisic acid 



CH 2 COOH 

 CH 2 .CHNH 2 .COOH 



The tyrosine must first be reduced to phenylalanine 



CH 2 .CHNH 2 .COOH 



and then this substance must undergo oxidation into homogentisic acid. 

 Since phenyl lactic acid and phenyl pyruvic acid, but not phenyl acetic 

 acid, are also converted in alcaptonuric patients to homogentisic acid, it 

 has been suggested that these two substances form stages in the conversion of 

 phenylalanine into homogentisic acid. Thus 



-> H0 



\/ \ J OH 



CH 2 CHOH.COOH CH 2 CO.COOH CH 2 COOH 



Phenyl lactic Phenyl pyruvic Homogentisic 



It is further thought that under normal circumstances the phenyl deriva- 

 tives, tyrosine and phenylalanine, are oxidised to homogentisic acid as in the 

 alcaptonuric patient. In the normal individual, however, the introduction of 

 two hydroxyl groups into the benzene ring leads to some process, perhaps 

 of a ferment character, which breaks up the ring. This ferment is absent 

 in the alcaptonuric, so that the transformation of the phenyl derivatives 

 stops short at the stage of homogentisic acid (Garrod). The eminently 

 specific character of this process is shown by the fact that although these 

 various substances undergo complete oxidation in the body, a slight modifi- 

 cation in the chain of the processes renders the change impossible. Thus 

 if the side group in phenyl lactic or phenyl pyruvic acid be converted to 

 acetic acid before the introduction of the two OH groups into the phenyl 

 ring, the phenyl acetic acid thus produced is incapable of undergoing further 

 oxidation. Tyrosine in the intestine undergoes deamination to form 

 oxyphenyl propionic acid and oxyphenyl acetic acid. These cannot be 

 further oxidised, but appear in the urine as such or, after conversion into 

 kresol or phenol, as sulphuric acid esters. 



Somewhat similar conditions apply to the oxidation of tryptophane. 



