FREE AMINO ACIDS OF BLOOD AND URINE 255 
of free amino acids, related to a common pathological process which may be due 
to distinct causative factors. 
The proposed practical classification may now be developed as follows: 
A. Aminoaciduria resulting from a congenital metabolic block involving one or more 
amino acids 
According to the “one enzyme-one gene” theory if, in an enzymatically driven 
sequence of reactions, one particular enzyme is missing, there is a metabolic block 
at the stage of the missing enzyme as a result of the genetic defect. If no alternative 
metabolic pathway is available, there will be an accumulation of the precursors 
which may result in harmfull effects on the tissues and in urinary hyperexcretion of 
these precursors. In this category we classify the following types of aminoaciduria 
which are very infrequently met: 
1) Lesion of phenylalanine metabolism. In phenylpyruvic oligophrenia there is an 
increased level of plasma phenylalanine and hyperexcretion of this amino acid as 
well as of its derivatives (phenylpyruvic, phenyllactic, phenylacetic, #-phenol- 
acetic, p-phenollactic acids and phenylacetylglutamine). Oxidation of phenyl- 
alanine into tyrosine is impaired and tryptophane metabolism seems also to be 
involved since there is a hyperexcretion of indoleacetic, indolelactic and indoxylacetic 
acids. Phenylalanine clearance is said to be normal. 
2) Lesion of tyrosine metabolism. It is not well established whether alcaptonuric 
urines show evidence of abnormal amino acid excretion. According to PELC AND 
Vis®8, there is an increased tyrosine and phenylalanine excretion as well as the ap- 
pearance of an unidentified unhydrolyzable constituent, yielding a yellow color on 
reaction with ninhydrin, which presumably is homogentisic acid. One case of tyrosi- 
nosis has been described by MEDEs in 1932 in a patient suffering from myasthenia 
gravis, who excreted large amounts of p-phenolpyruvic acid. It was noticed that 
phenylalanine intake produced tyrosine hyperexcretion w thout alcaptonuria. The 
reality of an authentic biochemical lesion has been questioned since it is well esta- 
blished now that pyruvic acid hyperexcretion may result from acquired hepatic in- 
sufficiency, from malignant growths and from vitamin C deficiency (see p. 258 and 259). 
3) Lesion of tryptophane metabolism. In Hartnup syndrome, described by Baron 
et al.69, there is a more or less generalized hyperaminoaciduria associated with indican 
as well as indoleacetic acid hyperexcretion. The biochemical lesion concerned here 
impairs tryptophane conversion into nicotinic acid. 
4) Lesion of valine, leucine and isoleucine metabolism. There is an “overflow” amino- 
aciduria involving valine, leucine and isoleucine present in a syndrome known as 
“maple-sugar-urine disease”, 71 in which urine smells like maple syrup. Urine also 
contains large amounts of the corresponding a-keto acids. The metabolic block has 
been definitely located by Dancis et al.7* who showed that desamination of the three 
branched-chain amino acids normally occurs but that the resulting keto acids 
cannot undergo further degradation by oxidative decarboxylation. 
5) Lesion of phosphoethanolamine metabolism. In a condition known as hyperphos- 
phatasia, there is a metabolic block bearing on phosphoethanolamine hydrolysis, 
resulting in an accumulation of this intermediate metabolite and its urinary 
hyperexcretion. 
References p. 261/262 
