Enzymes 67 



galactose- 1 -phosphate to glucose-uridine di-phosphate (UDP). 

 This complex would normally break down to UDP-galactose and 

 glucose. As a result, less glucose than normal is made available and 

 there is loss of calories and ATP. The clinical features of the dis- 

 ease are due to these effects and also to toxic effects of the accumu- 

 lated galactose. 



D. Amino Acid Metabolism 



A well known example of a genetic enzyme inadequacy is 

 phenylketonuria. Here there is absence of a liver enzyme that in the 

 presence of TPN and oxygen converts phenylanine to tyrosine. The 

 accumulated phenylalanine breaks down to toxic products, that 

 damage the nervous system, mental deficiency forming a prominent 

 feature of the clinical syndrome. Normal people fed large doses 

 of phenylalanine do not produce these toxic products (phenylpyru- 

 vic, phenylacetic and phenylactic acids and phenylacetylglutamine). 

 Their formation may indicate a further genetic abnormality or be 

 an adaptive mechanism developed in response to long-continued 

 high tissue levels of phenylalanine. One suggested mechanism for 

 the toxicity of phenylalanine derivatives is interference with the 

 enzyme 5-hydroxytryptophane decarboxylase which is needed for 

 the synthesis of 5-hydroxytryptamine, a possible transmittor of 

 impulses in the brain. Patients with this disease also show deficient 

 melanin production. This defect is due to inhibition by phenyl 

 alanine of the enzyme tyrosinase that catalyses the first step in the 

 production of melanin from tyrosine. 



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Baldwin, E. (1957) : Dynamic Aspects of Pathology, 3rd ed. Cambridge 



University Press. 

 Billing, B. H. and Lathe, G. H. (1958) : Amer. J. Med., 24 .1 11. 

 British Medical Bulletin (1954) : Reactions to Injury, vol. 10. 

 Dawkins, M. J. R., Judah, j. D. and Rees, K. R. (1959) : /. Path. Bart.. 



77:257. 

 Gallagher, C. H., Judah, J. D. and Rees, K. R. (1956) : Proc. Roy. Soc. 



B., 145:154, 195. 

 Harris, H. (1959) : Human Biochemical Genetics. Camb. Univ. Press. 



