Amino acids excretion

The amounts of single amino acids excreted in urine in the conjugated form, as determined independently by Stein and Muting, are given in Tables 1 and 2. According to Stein, glycine, glutamic acid, aspartic acid, histidine, and proline are quantitatively the most important amino acids liberated in the course of urine hydrolysis. Serine, lysine, tyrosine, cysteine and cystine, threonine, alanine, valine, phenylalanine, and leucine are... 

In the course of studies on other pathological amino acidurias, the accompanying peptiduria has also been observed by many authors. Rapp de Eston et al. (R2) observed a marked increase in the excretion of both free amino acids and peptides in patients with diffuse hepatic necrosis. Using a simplified chromatographic method adapted to clinical purposes and suitable for analysis of amino acids excreted with urine, Skarzynski et al. (S5) demonstrated a raised level of a certain peptide which is always present in normal urine in smaller quantities, as well as the appearance of some new peptides in cases of jaundice and liver cirrhosis. Some abnormal peptide spots were also detected on the chromatograms in cases of progressive muscular dystrophy (K4) and in patients irradiated with X-rays (S2). 

With respect to amino acid excretion Woodson and co-workersl3 and othersl4,15 have found by microbiological methods large variations. Stein 16 obtained evidence of wide variations in the amino acid excretion of cystinurics. Further data are also available with respect to creatine and creatinine excretion which bear out our conclusion regarding individuality of excretion patterns. 17,18,19... 

The fact that amino acid excretion patterns (p. 111), amino acid salivary patterns (p. 65), and amino acid duodenal juice patterns (p. 68) are distinctive for each individual is in line with the idea of distinctive needs. That there are wide ranges (presumably distinctive for each individual) in the content of blood plasma (p. 60) with respect to individual amino acid points in the same direction. 

Uric acid is the end product of the purine metabolism. When uric acid excretion via the kidneys is disturbed, gout can develop (see p. 190). Creatinine is derived from the muscle metabolism, where it arises spontaneously and irreversibly by cyclization of creatine and creatine phosphate (see p. 336). Since the amount of creatinine an individual excretes per day is constant (it is directly proportional to muscle mass), creatinine as an endogenous substance can be used to measure the glomerular filtration rate. The amount of amino acids excreted in free form is strongly dependent on the diet and on the ef ciency of liver function. Amino acid derivatives are also found in the urine (e.g., hippu-rate, a detoxification product of benzoic acid). 

Amino acid excretion appears to be within the normal range and no characteristic pattern has been described. 

Substances Included in the Expression Amino Acid Excretion... 

In recent years, amino acid excretion has been more and more investigated in terms of blood clearance, and this method has contributed usefully to our knowledge of the mechanism involved in pathological conditions (C13, E5, P2). Ratios of a given amino acid output to its blood plasma level undoubtedly yield instructive information. There are three points however that deserve close consideration if misleading interpretations are to be avoided. 

Quite independently of these considerations concerning blood clearance, it is obvious of course that investigations dealing with renal reabsorption or tubular secretion are most important in the study of amino acid excretion in the urine. 

Pentz et al. (P5) estimate taurine with fluorodinitrobenzene in urine passed through Dowex 50 H+ columns, but there are doubts as to whether this procedure is really specific for taurine (B38). Dent et al. have compared results obtained for the estimation of sulfur-containing amino acids in urine of cystinuric patients, by polarographic and microbiological methods (D18, D19). Hier (H12) and Schreier and Pliickthun (S10, Sll) have published data on amino acid excretion as determined microbiologically. Enzymatic methods have been used with success in the case of histidine in urine with specific decarboxylase preparations (S23). 

In children above 2 years of age, the situation is not substantially different from adults as far as the relative amounts of amino acids excreted are concerned. In fact, only very few really satisfactory data have been obtained so far in urines from children above 2 years of age. We present therefore in Fig. 3 a typical chromatogram of a 24-hr specimen of urine of a normal child, 2 years old, as drawn from Vis observations. Comparison of quantitative data concerning daily excretions are rendered difficult because of the differences in body size. The 24-hr basis alone is not suitable. It is necessary to compare data on the basis of percentage of total nitrogen excretion, or per kilogram of body weight, a procedure adopted by Jonxis and Huisman. We do not believe it suitable or safe to choose a comparison factor based on creatinine excretion. 

In early infancy the situation is known to be quite different from that among older children. Simon noticed in 1911 that the newborn infant excreted 10 % of its total nitrogen output in the form of amino nitrogen, whereas in adults it drops to 2 % (S15). This was confirmed in later years (B4, Cll, G5) and extended to the study of individual amino acid excretion by microbiological methods (S10, Sll), by paper chromatography (S20, S21), and finally by ion exchange column chromatography (D28, D30) at the time Moore and Stein s first method of 1951 was still the only one available. 

It has been claimed that calcium gluconate infusions reduce both phosphate and amino acid excretion (R4, R5). This has been only partly confirmed (F20) and needs to be further investigated. 

A similar condition of malnutrition has been described in Europe ( Mehlnahrschade ), and in Italy it has been studied from the point of view of amino acid excretion in three patients (M4). 

Abnormal patterns of amino acid excretion in the urine have been described in a wide variety of pathological conditions. So far, their description has led very frequently to quite confusing pictures when all... 

Amino acid excretion in urine varies with maturation of renal tubular function. Premature infants, especially during the first week, have a generalized physiological renal aminoaciduria (see Figure 20-2) even at full term, aminoaciduria is more pronounced than in normal adults. In the urine of normal adults, glycine is usually the dominant fraction, with alanine, serine, glutamine, and— in indulgent meat eaters— histidine and 1-methylhistidine present in smaller quantities. In some normal urine, taurine is prominent in others, (3-aminoisobutyric acid is seen. 

Figure 20-2 Two-dimensional chromatograms of urine showing the variability of amino acid excretion with age. A, Neonate. B, Infant. C, Adult. /, Alanine 2, serine 3, glycine 4, glutamine 5, histidine 6, lysine/ornithine.

Liver and Red Cell. The identification by Westall (W3, W4) of the amino acid excreted in large amounts as an intermediate in the urea cycle led him to postulate a deficiency of argininbsuccinate lyase in this condition. He confirmed this in the red cells of two affected children. In all other cases of argininosuccinic aciduria in which this assay has been performed, no enzyme activity has been detected in the red cells... 

Tryptophan malabsorption (blue diaper syndrome) Indigo blue and other indoles (amino acid excretion is normal) Tryptophan Hypercalcemia, retarded growth, febrile episodes, and irritability Chromatographic separation and detection of indole derivatives (H21, S36) (D16, R9, T3a)... 

A7a. Armstrong, M. D., Yates, K. N., and Connelly, J. P., Amino acid excretion of newborn infants during the first twenty-four hours of life. Pediatrics 33, 975-978 (1964). 

Stambaugh, R., and Davidson, D. T., Evaluation of the amino acid excretion pattern of mental retardates as a screening technique for inborn errors of metabolism. J. Pediai. 66, 301-303 (1964). 

E3. Estes, F. L., and Blocker, T. G., Amino acid excretion after thermal bum. Texas Kept. Biol. Med. 24, 54-66 (1966). 

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