Amino Acid Excretion Patterns Research Articles

Evaluation of the amino acid excretion pattern of mental retardates as a screening technique for inborn errors of metabolism

I N ~ E C E N T years a great deal of effort has been directed to a search for the inborn errors of metabolism associated with mental retardation utilizing the amino acid excretion pattern as a research tool. Indeed, many of the known types of metabolic defects associated with mental retardation have been found because they alter either directly or indirectly the amino acid excretion pattern of the retardate. In this study, we have used the amino acid excretion pattern as a screening technique for inborn errors of amino acid metabolism in 500 retarded persons examined at this center. Total nitrogen excretion, consisting mainly of urea, has been used by numerous investigators as a reference value for determining the degree of amino aciduria. 13 However, creatinine excretion shows less fluctuation than total nitrogen, 4 and the individual amino acid excre~on levels can be best related to creatinine excretion so that our values are recorded in micromoles of the amino acid per gram of creatinine.

The identification of homocystine in the urine

Methionine is an essential amino acid present in human blood plasma and normally excreted in small amounts in the urine. The normal pathway for the metabolism of methionine involves demethylation to homocysteine which in turn combines with serine to form cystathionine, an intermediate along the pathway to cysteine and cystine. During biochemical investigations of children with congenital anomalies, mental retardation and failure to thrive, several significant abnormalities in the pattern of the sulfur amino acid excretion were observed in a one year old male infant. To our knowledge, the presence of homocystine in urine has not been previously reported. This communication will serve to describe the isolation and identification of this amino acid. A complete clinical description of the patient and evaluation of the metabolic data will be published later.

Pattern of amino-acid excretion in urine of dystrophic children.

Pattern of amino-acid excretion in urine of dystrophic children.

The Pattern of Urinary Alpha Keto Acids in Various Neurological Diseases

During the past few years the normal pattern of urinary amino acid excretion, as determined by paper and column chromatography, has been established, and much information has been collected concerning deviations from the normal in an assortment of pathological conditions. Comparable information with respect to keto acid excretion is only now becoming available. The α-keto-acids are fairly unstable compounds, and, although a few methods have been described for their direct paper chromatography, all these suffer from inaccuracies induced by the decomposition of the acids in the process of extraction or development of the chromatogram. Therefore it has become general usage to convert these compounds to the stabler 2,4-dinitrophenylhydrazone derivatives. These products are then subjected to chromatography. The 2,4-dinitrophenylhydrazones (DNPH) are intensely yellow-to-orange compounds and can be localized on the filter paper in quantities as low as 2μg.-5μg., by either their intrinsic color or their ultraviolet light absorption. They may be

Observations on the urinary amino acid excretion in man: the influence of age and diet

Using the Dowex 50 column chromatographic technique of Moore and Stein, studies have been made of free amino acid excretion in 12 infants and two older children in order to evaluate the influence of age and of diet. Consideration has been given to various stand ards of reference for evaluating amino acid excretion, and it is concluded that it is best expressed in terms of creatinine excretion. In terms of creatinine excretion it was found that premature infants excrete roughly ten times as much free amino acid as do subjects ten or more years old, and that full-term infants excrete roughly three times as much as the older subjects. Our data on 10-year-olds reveal values virtually identical with those reported for adults. The pattern of individual amino acid excretion was found to differ in early life from that seen in older children and adults. A number of amino acids are present in greater amount and several are found only at that time of life. Hydroxyproline has been identified in the urine of premature and newborn infants. An unidentified ninhydrin reactant, designated as peak No. 9 is described which has not been observed in subjects more than 5 months old. The anomalous behavior of taurine is described, being present in large quantities in the neonatal period, virtually disappearing thereafter, and reappearing again in quantity by the tenth year. Certain late effects of prematurity are described. The effects of diet on amino aciduria are considered, the indications being that the amino acid output in the urine is influenced to some extent by the diet. Comparisons were made of free amino aciduria on a diet of whole protein (milk) and on a synthetic diet supplying nitrogen as a mixture of natural amino acids. Certain differences were encountered the significance of which is discussed. The disappearance of peak No. 9 on the amino acid diet was particularly striking. Some preliminary attempts to identify it are reported.

The Threonine Requirement of the Normal Infant

In studies designed to evaluate the threonine requirement of normal infants a synthetic diet was employed which provided nitrogen in the form of a mixture of 18 essential and non-essential amino acids, all as the natural L-isomers. It was found that infants would gain weight normally and exhibit every sign of health on such a diet, although a somewhat higher than average caloric intake was at times required. By graded reduction of the threonine intake, threonine being replaced by glycine, the minimum threonine requirement was determined. This was found to be approximately 60 mg per kilogram per day for infants between one and 6 months of age. A deficiency of threonine was associated with failure to gain weight and with impaired retention of nitrogen. There was increased loss of nitrogen in the urine, but no increased amino aciduria. Certain changes in the amino acid excretion pattern were observed, notably a decreased threonine excretion.