Gene Action and Polypeptides 



405 



henceforth restricted to the recessive form of 

 this disease. 



Alcaptonuria is clearly an inborn error of 

 metabolism and results in the daily excretion 

 of several grams of alcapton. A study of 

 the biochemistry of alcaptonurics shows that, 

 of numerous substances tested, only alcapton 

 appears in abnormal quantities in the urine 



or blood, and that the reducing properties of 

 the urine can be attributed entirely to the 

 alcapton it contains. These results suggest 

 that we have traced the pedigree of causes 

 back to, or very close to, the primary effect 

 of the gene. 



If alcapton is a substance produced by the 

 abnormal gene, it should be absent in homo- 



figure 32-1. Sequence of chemical substances involved in the formation and 

 metabolism of alcapton. 4 = homogentisic oxidase, 5 = isomerase, 6 - hydro- 

 lase. 3 involves two reactions — first an oxidation to 2,5-dihydroxyphenylpyruvic 

 acid, then oxidative decarboxylation. 



H— C 

 H— C 



■ 



. 



C— H 

 C— H 



H— C 

 H— C 



C 

 H— C— H 



H-CNH 2 

 COOH 



Phenylalanine 



OH 



C— H 



i 

 C— H 



C 



H— C— H 



H-CNH 2 

 COOH 



Tyrosine 



o 



H— C CHo H 



C— COOH 

 H 



HOOC-CH 



HC • COOH 



Fumaric acid 



H— C' 

 H— C 



OH 



I 



. ' 



H 

 H 



C 



H— C— H 



c=o 



COOH 



p-OH phenylpyruvic acid 



I 3 



OH 



I 



H— C 

 H— C 



^ 



C— H H 



i 



OH 



C 



C— COOH 

 H 



Alcapton 

 (Homogentisic acid) 



■> CO, + H 2 



