The amino-aciduria in Fanconi syndrome. A study making extensive use of techniques based on paper partition chromatography

Publisher Website
Google Scholar
Abstract
The amino-aciduria in 3 cases of Fanconi syndrome was investigated with paper chromatograms. One case was more thoroughly investigated from other points of view over a period of 4 mos. The amino-aciduria was renal in type, i.e., due to a low kidney threshold for amino-acids. The total output of amino-nitrogen in the urine was related to the output of glucose according to a straight line relationship, although botl varied considerably from day to day. It also appeared to be related directly to the fluid balance of the patient. The following free amino-acids were found in the urine of 1 case (where the 24 hr. output of amino-acid was roughly estimated it is given in parentheses): cystine, aspartic acid, glutamic acid, serine (0.25 g.), glycine (0.8 g.), threonine (0.5 g.), alanine (1.0 g.), valine (0.5 g.), leucine and/or iso-leucine (0.4 g.), methionine (0.34 g.), phenylalanine, tyrosine (0.5 g.), arginine, citruline, histidine, proline, hydroxyproline and [alpha]-amino-n-butyric acid. Cysteic acid and methionine sulfoxide were sometimes present but may have been produced by secondary decomposition of cystine and methionine. A ninhydrin-reacting substance "over-glycine" was found. It is suggested that this is a new amino-acid and its behavior on the chromatogram suggests that it is of novel composition. A pep tide "under-alanine" containing serine and glycine was also found in large amounts. In one case 0.75 g. at least was excreted daily in the urine. It is believed to be serylgly-cylglycine, but this has yet to be confirmed by synthesis. Complexes liberating large amts. of aspartic and glutamic acids on hydrolysis were also present. No error in metabolism of sulfur amino-acids could be shown in one case of Fanconi syndrome specially investigated. After methionine was given by mouth, the output of [alpha]-amino-n-butyric acid increased as if some direct desulfurization had taken place. This is apparently a normal mechanism. There was also a large increase in the output of methionine sulfoxide. This has also been found in normal subjects. Its possible formation in the urine from methionine by secondary oxidation in storage has not been adequately excluded. It has not been possible to prove that the chronic loss of amino-acids in the urine is responsible for the other features of the syndrome. [alpha]-Amino-n-butyric acid and "under-alanine" have been found in normal plasma and urine. Developments in the technique of paper chromatography have been devised to enable: (a) small quantities of substances in biologic fluids to be isolated for further study of their chemical properties; (b) the simultaneous detection of histidine, histamine and tyrosine in urines; (c) the detection of methionine and cystine without loss from decomposition and without confusion with other amino-acids. It has been shown that most of the common organic and inorganic substances present in urine, and many others present in pathologic conditions, have characteristic movements on the paper chromatograms which are sufficiently specific to constitute a criterion for their recognition. Further, by means of this technique, the existence of new compounds may be disclosed.