276 



CHAPTER 31 



If alcapton is not produced by the gene for 

 alcaptonuria, but is a normal metabolic inter- 

 mediate, it may have chemical precursors. 

 If such a chemical precursor is added to the 

 diet of alcaptonurics, it should be converted 

 to alcapton which should be excreted in 

 increased amounts. When alcaptonurics are 

 fed an excess of glucose, the amount of al- 

 capton found is unchanged, indicating that 



glucose is not a precursor of alcapton. But, 

 if p-OH phenylpyruvic acid, or if either of 

 the amino acids tyrosine or phenylalanine is 

 increased in the diet of alcaptonurics, their 

 excretion of alcapton is increased almost 

 correspondingly. Accordingly, it can be 

 postulated that there is a series of chemical 

 precursors of alcapton (Figure 31-3). In 

 the scheme illustrated, phenylalanine is nor- 



FIGURE 31-3. Sequence of chemical substances involved in the formation and metab- 

 olism of alcapton. 4 = homogentisate oxidase, 5 = isomerase, 6 = hydrolase. 



H-C 



II 

 H-C 



%. 



I 



C-H 

 C— H 



H-C-H 



I 

 H— CNH2 



COOH 

 Phenylalanine 



H— C 



II 

 H-C. 



H- 



./ 



OH 

 I 

 C.v 



-H 



C- 



I 



H— CNH2 



COOH 

 Tyrosine 



OH 



I 



/^^ 

 H-C C— H 



II I 



H-C. X— H 



C 



I 



H— C— H 



I 

 COOH 



p-OH phenylpyruvic acid 



la 



HOOC • CH 



II 

 H-C 



CO 



I 

 CH2 



CO 



H-C 



II 

 H-C 



O 



II 



CH, 



I 

 C— 



CH2 • COOH 

 Fumaryiacetoacetic acid 



^c II 

 o o 

 o 



H 



H 

 I 

 -C— COOH 



I 

 H 



H-C 



II 

 H-C 



OH 



I 

 C, 



^C^ 



I 



OH 



HH 



I 

 — C— COOH 



I 



H 



HOOC-CH 



II 

 HC-COOH 



Fumaric acid 



Maleylacetoacetic acid 



CH3 

 CO 



I 



CH2-COOH - 

 Acetoacetic acid 



Alcapton 

 (Homogentisic acid] 



CO2 -t- H2O 



