THE METABOLISM OF l-TYROSINE IN INFANTILE SCURVY 1

Abstract

Attention has been drawn by Levine, Marples, and Gordon (1) to the relationship between ascorbic acid and the urinary excretion of aromatic amino acid intermediates by the normal premature male infant, both during periods of high protein intake and supplemental tyrosine and phenylalanine ingestion. To our knowledge, no reports have been forthcoming of similar studies with older, ascorbic acid depleted subjects.3 This communication is concerned with the metabolism of l-tyrosine in infantile scurvy. Observations have been made on the urinary excretion products, the serum content of both hydroxyphenyl compounds and amino acid nitrogen.Sealock and his co-workers (2) have demonstrated that the oral administration of l-tyrosine to scorbutic guinea pigs results in the urinary excretion of the amino acid and its two principal deaminated products, parahydroxyphenylpyruvic and parahydroxyphenyllactic acids. A proof that this metabolic disorder is primarily dependent upon the state of ascorbic acid depletion is afforded by the observation that the tyrosyluria (hydroxyphenyluria) is abolished when the vitamin is given orally or parenterally.Certain liver extracts are capable of modifying an induced tyrosyluria ( 1, 3), and recently Woodruff and Darby (4, 5) have indicated that pteroylglutamic acid (PGA) exerts a similar effect in the depleted guinea pig maintained on a basal scorbutogenic diet with supplements of l-tyrosine. By the administration of PGA to normal premature infants, Govan and Gordon (6) established by dietary cow's milk protein. Several in vitro studies on the respiration of liver preparations with tyrosine as a substrate (7-9) tend to confirm that ascorbic acid, PGA, and certain liver fractions are concerned with the complete metabolism of tyrosine.The appearance of alkaptonuria during periods of high aromatic amino acid consumption has been noted in the albino rat (10) and in the scorbutic guinea pig ( 11 ), but the excretion of homogentisic acid by human subjects in a state of ascorbic acid depletion has not been reported.The present investigation is concerned with the effect of ascorbic acid, PGA and vitamin B12, on the urinary and serum tyrosyl content of several infants with clinical and preclinical scurvy during supplemental l-tyrosine feedings. METHODSUrine specimens were collected under toluene and stored at 4°C. Metaphosphoric acid was used in addition to toluene as a preservative when urinary ascorbic acid analyses were undertaken. Blood samples, when required, were obtained by internal jugular puncture approximately one and one-half hours after feeding. The sera were kept frozen until their amino acid nitrogen. and hydroxyphenyl content had been estimated. All colorimetric estimations were made with either a Coleman Junior spectrophotometer or an Evelyn photoelectric colorimeter. 1) Total Urinary Tyrosyl (Hydroxyphenyl) Compounds These were estimated by the method of Folin and Ciocalteau as modified by Medes (12) and adapted to the spectrophotometer at a wavelength of 465 muA. 2) Urinary Tyros...

An inborn defect in the metabolism of tyrosine in infants on a normal diet

“…Ascorbic acid promptly cured the hydroxyphenyluria in these infants (Levine et al 1939(Levine et al , 1943Woolf & Edmunds, 1950) and it rarely appeared in an infant that had ever been fed with ascorbic acid. Adults or infants suffering from scurvy also showed hydroxyphenyluria when fed with large doses of tyrosine (Rogers & Gardner, 1949;Morris, Harpur & Goldbloom, 1950) and here again feeding with ascorbic acid cured the hydroxyphenyluria. Independently of the above work, Sealock & Silberstein (1939, 1940 had shown that scorbutic guinea pigs developed hydroxyphenyluria if they were fed with tyrosine.…”

“…None of the mothers showed signs of ascorbic acid deficiency during pregnancy, and seven of them took supplementary ascorbic acid. It seems improbable that these infants lacked ascorbic acid, and in any case deficiency of this vitamin will not produce hydroxyphenyluria unless the premature infant or scorbutic infant or adult is also given a high-protein diet or a 'loading' dose of phenylalanine or tyrosine (Levine et al 1939(Levine et al , 1943Woolf & Edmunds, 1950;Rogers & Gardner, 1949;Morris et al 1950).…”

Tests for Phenylketonuria

“…p-Hydroxyphenylpyruvic acid occurs in the urine of infants fed large doses of tyrosine or phenylalanine (Levine, Marples, andGordon, 1939, 1941 ;Levine, Dann, and Marples, 1943;Woolf and Edmunds, 1950), of sufferers from scurvy (Rogers and Gardner, 1949;Morris, Harpur, and Goldbloom, 1950), of adults and children with hepatic cirrhosis (Felix, Leonhardi, and Glasenapp, 1951 ;Woolf, unpublished), and, as briefly reported above, of a number of normal infants (Gibbs and Woolf, in preparation). It is difficult to distinguish p-hydroxyphenylpyruvic acid from phenylpyruvic acid by using ferric chloride or 2:4-dinitrophenylhydrazine; the two acids can be differentiated by using phenistix and observing the colour on the strip, but not if the reagents on the strip are leached out into the urine.…”

Ascorbic acid and tyrosine metabolism in preterm and small-for-dates infants.

“…It has been reported that scorbutic subjects given a load of L-tyrosine excrete large amounts of tyrosine and its metabolites-a defect that is eliminated by administration of ascorbic acid (Rogers and Gardner, 1949a, b;Morris, Harpur, and Goldbloom, 1950;Huisman and Jonxis, 1957;Mohanram and Reddy, 1974). A transient defect in tyrosine oxidation has also been commonly observed in preterm infants fed on high protein diets (Levine, Marples, and Gordon, 1939;Levine, Gordon, and Marples, 1941;Matthews and Partington, 1964;Rizzardini and Abeliuk, 1971;Prasad, Sinha, and Sen, 1972).…”