Urinary Excretion Of Amino Acids Research Articles

Effect of Gastrointestinal Surgery and Bacterial Overgrowth on the Urinary Excretion of Sulfur Amino Acids and Their Main Degradation Products

The urinary excretion of sulfur amino acids and their main degradation products was determined in patients subjected to various forms of gastrointestinal surgery or with bacterial overgrowth. A normal excretion of total sulfur and inorganic sulfate was found, indicating an adequate intake and maintained ability to absorb sulfur amino acids. An increased excretion of ester sulfate was observed in all groups except patients subjected to ileocecal resection or proctocolectomy, probably owing to bacterial overgrowth. A reduced excretion of methionine was observed in patients with gastric resection (Billroth I), ileocecal resection, and abnormal gut flora, whereas patients with jejunoileal bypass showed an increased excretion of methionine, probably a consequence of the impaired liver function. For cystathionine, a similar effect was found in patients with ileocecal resection and jejunoileal bypass. A reduced excretion of mercaptolactate was found in jejunoileal bypass patients. A low excretion of thiosulfate was seen in proctocolectomized patients, suggesting that the bacterial flora of the colon plays a role in the formation of thiosulfate. A low excretion of thiocyanate was found in gastric-resected patients, which may be due to a decreased ability to hydrolyze cyanogenic and/or thiocyanogenic glycosides or to a reduced intake of these compounds.

Partial substitution of amino acids of a parenteral solution with tripeptides: Effects on parameters of protein nutrition in baboons

We previously showed that triglycine and trileucine are efficiently utilized when infused intravenously (IV) in baboons who are fed a complete diet orally. In the present experiments we investigated the utilization of these tripeptides in the context of total parenteral nutrition. A group of subhuman primates (baboon) was subjected sequentially to two forms of total parenteral nutrition, each for a period of six days. The only difference between the two periods was that in one, all amino acids were given in free form, and in the other, the glycine and leucine components of the amino acid mixture were replaced with triglycine and trileucine, respectively. During both experimental periods the infusion solution provided daily 100 calories/kg body weight and 2.5 g amino acids/kg body weight. There were no significant differences between nitrogen balance, plasma amino acid concentrations, or urinary excretion of amino acids for the two forms of parenteral nutrition. The only exceptions were a greater plasma concentration of isoleucine and a greater urinary excretion of leucine during infusion of the partial peptide solution. Assimilation of triglycine and trileucine under the conditions of total parenteral nutrition was assessed by determining concentrations of these peptides in plasma and urine. Trileucine was not found in plasma, and only 1.8% of the amount of trileucine infused appeared as trileucine and dileucine in urine. Triglycine was detected in plasma and 17.1% of the amount of triglycine infused was excreted in urine as triglycine and diglycine. These data suggest that assimilation of trileucine and triglycine under the conditions of our experiment was sufficiently efficient to meet the daily need for an essential amino acid (leucine) and for nitrogen (glycine).

Utilization of intravenously infused tripeptides in baboons: Effect on plasma concentration and urinary excretion of amino acids

When baboons, while consuming an adequate diet, were infused continuously for 3 days with parenteral solutions (1l/day) containing either triglycine (50 mM) or trileucine (5 mM) there was either no or very little accumulation of these peptides either in plasma or urine. The increases in plasma concentrations of glycine or leucine and urinary excretion rates of these amino acids during the infusion of the above tripeptides were similar to those found when baboons were infused with parenteral solutions containing either glycine (150 mM) or leucine (15 mM). These data show efficient utilization of tripeptides under the condition of continuous infusion and encourage further investigation of tripeptides as substrates for parenteral nutrition.

Accumulation of acid soluble peptides in rat liver in vivo after injection of bestatin.

Intraperitoneal injection of bestatin, a microbial aminopeptidase inhibitor, resulted in accumulation of acid soluble peptide-form amino acids in liver of fasting rats. This aminopeptidase inhibitor caused a slight increase in the rate of urinary excretion of acid soluble peptide-form amino acids. However, the excretion rates of only two amino acids of the acid soluble peptide-form were statistically higher in the bestatin injected rats than in the control rats. Leupeptin, another microbial protease inhibitor, also resulted in peptide accumulation in liver of fasting rats. However, it was less effective than bestatin. Leupeptin did not show any effect on the rate of urinary excretion of acid soluble peptides in rats under the present experimental conditions. These results suggest that bestatin sensitive protease (s) may participate in the process of protein degradation in the liver (and presumably in other tissues also), especially in the steps of the degradation of oligopeptides into amino acids.

Experimental renal failure rats induced by adenine. Evaluation of free amino acid, ammonia nitrogen and guanidino compound levels.

The levels of free amino acid, ammonia nitrogen and guanidino compounds were examined in renal failure rats induced by adenine. Among the essential amino acids in the serum, the marked reduction of lysine, valine, leucine and isoleucine was confirmed in the adenine-fed group as compared with the control group. Tyrosine and ornithine were also significantly reduced in the adenine-fed rats, while glycine, arginine and aspartic acid were significantly elevated. The urinary excretion of leucine, isoleucine and non-essential amino acids (glutamic acid, histidine, aspartic acid, citrulline, tyrosine, ornithine) was found to be high. On the other hand, adenine administered orally caused hyperammonemia. Furthermore, the results of the present study show that intake of adenine increased extraordinarily the level of guanidinosuccinic acid and methylguanidine in the serum, while the value of serum guanidinosuccinic acid and methylguanidine in rats fed on a control diet was not detectable.

Urine and calculus amino acids in the different types of urolithiasis.

Urinary amino acid excretion levels were estimated by paper chromatography in 15 control subjects and 27 stone formers classified according to stone type: (a) 15 cases with calcium oxalate stones, either pure or mixed with calcium phosphate and/or uric acid; (b) 6 cases with pure uric acid stones and (c) 6 cases with magnesium-ammonium phosphate stones, either pure or mixed with ammonium urate, also the free amino acid contents of the calculi of different types were estimated. The data revealed that there was a significant decrease in the amino acid excretion in all stone formers; the individual amino acid patterns varied according to the type of stone formed. This decrement in amino acid excretion could be attributed to: (a) a metabolic defect in the pathway of glycine, especially in the calcium oxalate cases; (b) the precipitation and/or adsorption of the free amino acids on the material of the calculi, which is demonstrated in 10 calculi, and (c) to a lesser extent to bacterial infection.

Renal transport of lysine and arginine in cystinuria.

To study the defective transport mechanism of cystinuria, renal tubular reabsorption of lysine or arginine in normal and cystinuria subjects was investigated by increasing the filtered load employing intravenous amino acid infusion. In the normal group the amino acid reabsorption rose with increases of the filtered load and reached a maximum (Tm). In the cystinuria group the elevation of amino acid reabsorption was poor at low filtered loads and some of the reabsorption rates fell below zero, whereas the tubular transport proceeded at a normal rate with a great increase of the filtered load. This might be explained as follows: At low filtered loads the filtered amino acid in the tubular lumen in patients with cystinuria is not absorbed into the cell because of a transport defect of the luminal membrane of the tubular cell, causing a large amount of urinary amino acid excretion. At high filtered loads the accumulated intraluminal amino acid permeates the tubular cell by a passive diffusion and is transported to the capillary across the intact basolateral membrane, which in turn only brings about a small urinary loss of amino acid. The infusion of lysine or arginine depressed the percentage of tubular reabsorption of other dibasic amino acids in both groups. In the cystinuria group the percentage of the dibasic amino acid reabsorption dropped sharply with an initial load of the inhibitor, but no more depression of the percentage of reabsorption occurred with further loads of the inhibitor.

Urinary excretion of sulfur amino acids and sulfur metabolites in burned patients receiving parenteral nutrition.

The urinary excretion of sulfur-containing compounds was studied in 11 burned patients during the first 10 days after injury. They were all given carbohydrate and fat by parenteral nutrition. Two patients also received large amounts of amino acids including methionine, whereas five patients were given amino acids including moderate amounts of methionine and cysteine. A sustained high excretion of mercaptolactate occurred in most patients. The excretion was not influenced by the type of parenteral nutrition, but related to the area of burned skin. A normal excretion of methionine, cyst(e)ine, inorganic sulfate, taurine, mercaptoacetate, thiosulfate, and thiocyanate was found at the end of the observation period in patients without amino acid therapy. Increased amounts of inorganic sulfate and methionine were excreted in patients receiving high doses of methionine, whereas an increased cyst(e)ine and taurine excretion was the most prominent finding in patients receiving moderate amounts of methionine and cysteine. These results indicate that burned patients have an unimpaired ability to metabolize sulfur amino acids. Patients not receiving amino acids or receiving moderate amounts of cysteine and methionine showed a negative sulfur balance, whereas patients given high doses of methionine maintained sulfur balance at near-zero levels. However, since signs of hepatic dysfunction appeared in the latter group, parenteral nutrition with amino acid mixtures containing high amounts of methionine is not recommended during the catabolic phase for burned patients.

Serum concentrations and urinary excretion of amino acids during total parenteral nutrition after abdominal surgery.

The effects of five days of postoperative total parenteral nutrition (TPN)—no oral intake—including a fat emulsion, Intralipid 20%, and varying amounts of amino acids and carbohydrates, on the fasting serum concentrations of amino acids, the nitrogen balance and the rate of urinary excretion of free amino acids were studied in three groups of patients, A, B and C, undergoing abdominal surgery. Group A was given 9.4 grams of nitrogen every 24 hours as 18 L‐amino acids in proportions corresponding to the amino acid composition of egg protein; groups B and C were given 9.3 and 13.9 grams of nitrogen every 24 hours, respectively, including the same 18 L‐amino acids in proportions corresponding to those present in human milk protein. During the first seven postoperative days, the changes in the serum concentrations of amino acids conformed largely to five patterns in all the groups. On day five, the serum concentration of methionine was higher in group B than in group C, whereas there was no difference in the urinary excretion rate for 3‐methylhistidine; this suggests that an increased supply of an amino acid may be reflected in a decrease in the fasting serum concentration of this amino acid administered. During the five days of TPN, the rate of urinary excretion of glycine and histidine decreased in all the groups. The 24‐hour urinary excretion of most of the amino acids administered was numerically greater in group C than in group B on all days studied with significant difference for methionine and valine on day five, whereas the excretion rate for amino acids expressed as a percentage of the total amount on a molar basis was similar for these groups. This suggests that an increase in the intravenous supply of amino acids in proportions corresponding to the amino acid composition of human milk protein is reflected in an increased rate of urinary excretion of the amino acids administered. The rate of urinary excretion of total nitrogen was similar in groups A and B. The nitrogen balance values showed efficient utilization of the two amino acids solutions studied, but no difference between them in this respect.

Treatment of generalized scleroderma with inhibitors of collagen synthesis.

Clinical evaluation of scleroderma and the urinary excretion of collagen specific amino acids and uronic acid indicate disease activity and have become a guide for treatment. During an experimental search for inhibitors of the synthesis of collagen and ground substance glycosaminoglycans, a few connective-tissue active agents were selected for therapy of scleroderma: D-penicillamine, benzyl-penicillin-diethylamino-ethylester-hydroiodide, L-glutamine, hydralazine, glucocorticoids, dextro-thyroxine, L-dopa, diphenylhydantion, chlorpromazine, and (+) catechine. Treatment for several years was required to bring about an arrest of progression in 89% of the patients, a regression in three-quarters, and subtotal or total recovery in more than 40%. Indications of favorable prognosis are youth, short disease history, a high total dose of agent, and long duration of the treatment.

Urinary copper losses in infants receiving free amino acid solutions

Plasma amino acids and the 24-h urinary excretion of copper and amino acids were measured in 18 infants receiving 0.4 g N/kg/day as free amino acids as part of a total parenteral nutrition regimen. Urinary copper excretion correlated positively with total excretion of alpha-amino nitrogen, in general, and the excretion of glycine, methionine, histidine, and lysine, in particular. Infants who received FreAmine II as compared to FreAmine III generally had increased plasma concentrations of glycine and methionine and increased urinary excretion of total alpha-amino nitrogen, glycine, methionine, and of copper. Chronic losses of copper in the urine of infants receiving free amino acid solutions may contribute to copper depletion and the development of a copper deficiency syndrome.

Some nutritional and physiological factors affecting the urinary excretion of acid soluble peptides in rats and women.

Urinary excretion of acid soluble peptide (ASP)-form amino acids was lower in rats deprived of protein than in rats fed on a 20% casein or 20% gluten diet. However, the amino acid pattern of urinary ASP was similar among each of the three dietary groups, suggesting that urinary ASP is mainly endogenous origin under these nutritional conditions. College women who were given a meat-free protein diet for 3 days after 10 days' protein deprivation excreted 1.4 times the amount of ASP-form amino acids during protein deprivation. The rate of urinary excretion of ASP-form amino acids in the state of protein deprivation was proportional to the metabolic body size of organisms as far as rats and women were concerned. Streptozotocin-induced diabetic rats excreted two times the amount of ASP-form amino acids compared with normal rats. This suggests that endogenous protein catabolism doubled in diabetic rats. When labelled urinary ASP was injected into rats, approximately 40% of the label was recovered as urinary ASP within 24hr. This excretion rate was far higher than that after the injection of free leucine. The rate of urinary excretion of ASP-form amino acids correlated with that of Nτ-methylhistidine in rats. These results favor the hypothesis that urinary ASP reflects the catabolism of body proteins.

Effect of Succinylation on the Protein Quality and Urinary Excretion of Bound and Free Amino Acids

Effect of Succinylation on the Protein Quality and Urinary Excretion of Bound and Free Amino Acids

Higher excretion of urinary bound amino acids in infants: probably related to protein-anabolic effect of growth hormone.

Concentrations of bound amino acids in urine were found to be markedly higher in infants than in children over 4 years of age. And it was also found that bound amino acid levels in plasma were increased in infants and young children than in adults. Urinary excretion of bound amino acids was increased in hypopituitary dwarf after one day of intramuscular injection of human growth hormone. A possibility was advanced that an increased excretion of bound amino acids of the overflow type observed in infants was due to active protein biosynthesis stimulated by growth hormone of which plasma levels have been reported to be high in infancy.

Renal tubular acidosis in childhood

Renal tubular acidosis in childhood

Cysteine supplementation to cysteine-free intravenous feeding regimens in newborn infants

To determine if cysteine is an essential amino acid for the intravenously fed newborn infant, growth parameters, nitrogen balance, plasma sulfur amino acid levels, and urinary amino acid excretion of premature and term infants were measured in the presence or absence of infused cysteine. Control intravenous formulations provided amino acids, including adequate methionine, carbohydrate, lipid, minerals, vitamins, and trace elements to all infants. Group and pair-matched comparisons showed that nitrogen retention, weight change, and growth in length and head circumference were not affected by cysteine supplementation of 77 mg/kg/24 h. The failure of cysteine supplementation to alter nitrogen retention was independent of postnatal age or gestational age. Plasma 1/2 cystine concentration was increased by 60% in the supplemented group with a concomitant 3-fold increase in urinary excretion of 1/2 cystine and taurine, but not of urinary methionine or cystathionine. Cysteine-supplemented infants exhibited a small increase in 3-methylhistidine excretion compared to pair-matched controls, suggesting that either an increase in muscle protein catabolism or an increase in muscle mass may have occurred.

1554 AMPICILLIN-INDUCED AMINOACIDURIA

In the process of performing metabolic screening tests using thin layer chromatography, we noted that 41 of 1,450 urine specimens(3%) contained both amino acids and ampicillin. When serum amino acid levels were measured, they were normal.In order to further delineate the nature of the aminoaciduria, urinary amino acid excretion was measured using high performance liquid chromatography in 10 patients receiving ampicillin. Urinary serine and glycine were elevated in all patients, aspartate and glutamate in eight, valine in seven, alanine and lysine in six and tyrosine in five. A minority had elevations in histidine, methionine and leucine.In an additional group of four patients, amino acids and beta2 microgobulins were measured in urine samples obtained before, during and after ampicillin administration. The increase in amino acid excretion could be demonstrated within 1-3 days after starting ampicillin, and was generally still present 2-3 days following completion of ampicillin therapy. Two of the four also had elevated urinary beta2 microglobulin levels. These findings suggest that ampicillin can damage the proximal tubule and impair the reabsorption of amino acids.In view of the frequent use of ampicillin, and the growing practice of screening for inborn errors of metabolism, the clinician should be aware that ampicillin can produce a generalized aminoaciduria.

638 THE RENAL HANDLING OF 3-METHYLHISTIDINE

The urinary excretion of the unique amino acid, 3-methylhistidine (3MH), has been proposed as a marker of endogenous protein catabolism and an index of a patient's metabolic state. Yet, the mechanisms of the renal handling of 3MH remain unclear. Consequently, we determined the simultaneous clearance of 3MH (C3MH) and inulin (Cin) in rats. Net reabsorption of 3MH was a consistent finding. In ten euvolemic animals, C3MH (313.2 ± 37.5 μl/min/100g BW) was less than Cin (1017.1 ± 21.2) and the percent 3MH reabsorbed was 72.6 ± 3.7%. In five volume expanded animals, the percent 3MH reabsorbed was not significantly altered (80 ± 5.0%). To confirm net reabsorption, 3MH combined with inulin was microinjected into proximal tubules of surface nephror Inulin recovery from the microinjected kidney averaged 102 ± 5% while the recovery of 3MH was only 74 ± 6% (P < 0.01). The percent of 3MH reabsorbed had no relationship to the quantity of 3MH injected, suggesting that there is no Tm for 3MH. This study clearly demonstrates that: 1) the renal clearance of 3MH is less than that of inulin, 2) net tubular reabsorption occurs over a wide range of filtered loads of 3MH and 3) a Tm for reabsorption of this amino acid metabolite could not be documented. These factors must be considered in using urinary excretion of 3MH as a marker of nutritional status.

Functional adaptation to reduction in renal mass: renal handling of amino acids by isolated perfused remnant rat kidneys.

To date, the renal handling of amino acids by remnant kidneys remains undefined. We have determined the renal handling of eight amino acids using the isolated perfused rat kidney. 6 normal and 22 partially infarcted rat kidneys (16 stage III [contralateral kidney removed], and 6 stage II [contralateral kidney left intact] were evaluated at perfusate amino acid concentrations approximately ten times normal plasma levels. Despite the reduction in glomerular filtration rate, the urinary excretion of most amino acids in remnant kidneys tended to exceed that of controls. Fractional amino acid excretion by both stage II and III kidneys tended to be or was higher than that of controls. The findings indicate that the fractional reabsorption of amino acids by residual nephrons of remnant kidneys is decreased. Our observations suggest that the changes are unrelated to a functional adaptation to the uremic environment.

SALLA DISEASE - CLINICAL AND BIOCHEMICAL FINDINGS

Salla disease is a recently described autosomal recessive lysosomal storage disorder. So far, 31 patients aged 3-63 years have been identified in Finland and one probable case in Sweden. The main clinical symptoms are early onset (3-6 months) and slow progression of severe psychomotor retardation (IQ 20-30), moderate or severe ataxia, slightly coarse facial features and good-humoured nature. There is no hepatosplenomegaly and the eyes are normal except for a diverging squint (50 %). EEG shows slowly progressive low-voltage, and 1/3 of the patients have convulsive episodes. Lysosomal storage is seen in several types of cells by electronmicroscopy: fibroblasts, sweat gland cells, Schwann cells, hepatocytes, Kupffer cells and cultured fibroblasts. The patients have vacuolated lymphocytes (1-15 %). Urinary excretion of amino acids, organic acids, glycosaminoglycans, and oligosaccharides is normal. The excretion of free N-acetylneuraminic acid is 10-15 times higher than normal. Preliminary studies indicate storage of free N-acetylneuraminic acid. So far, no enzyme defect has been detected, although a number of lysosomal hydrolases, including neuraminidase, have been assayed. Supported by the Foundation for Pediatric Research in Finland