Evidence Derived from Inborn Errors of Metabolism

Evidence Derived from Inborn Errors of Metabolism 

In discussing the use of mutants of microorganisms in the study of aromatic biosynthesis it was pointed out that valuable information could thus be obtained. An organism with a metabolic block rendering it unable to convert a substance X into its metabolite Y is likely either to excrete X, or to metabolize X by an alternative pathway if such is available, or to excrete metabolites of X formed by the action of relatively unspecific detoxicating systems. Accumulation or excretion of abnormal substances may therefore indicate an enzymic deficiency of this type. In the latter part of 

Diagram 6. Relationship of metabolic defects concerned with phenylalanine and tyrosine metabolism. For structural formulas see diagrams 8, 11, and 12. 

The metabolic defect involved in alkaptonuria w as suggested by Bateson (34) as early as 1902 to be inherited as a recessive Mendelian character, and later evidence has supported this prediction (395, 643). Gross (322) in 1914 concluded that it was due to lack of a specific enzyme. Alkaptonuria, unlike phenylketonuria, is not accompanied by mental symptoms and is not an incapacitating disorder except insofar as it may lead to ochronosis and arthritis (c/. 598). 

Additional interest arose when it was found possible to produce experimental alkaptonuria in animals. This can, for example, be brought about 

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IIIA. Evidence Derived from Inborn Errors of Metabolism... 

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