PROTEIN METABOLISM 871 



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

 is not possible to conceive of the direct conversion of 



HO /\ 



tyrosine into homogentisic acid OH 



NX 



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 homo- 

 gentisic 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 



/\ 

 HO 



OH 

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



Phonylalanine Phenyl pyruvic Homogentisic 



It is further thought that under normal circumstances the phenyl 

 derivatives, tyrosine and phenylalanine, are oxidised to homogentisic 

 acid as in the alcaptonuric patient. In the normal individual, how- 

 ever, 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 trans- 

 formation of the phenyl derivatives stops short at the stage of homo- 

 gentisic 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 modification 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. 



