The effect of aromatic amino acid supplementation on a1- antirypsin synthesis in oedematous malnutrition

OBJECTIVES: We have previously demonstrated that infected children with oedematous protein energy malnutrition have an impaired acute phase response to infection. We hypothesize that this impaired response is due to a relative shortage of aromatic amino acids. We therefore sought to determine whether supplementation of the diet of infected oedematous malnourished children with aromatic amino acids (70 mg/kg/d phenylalanine, 80 mg/kg/d N-acetyltyrosine, 30 mg/kg/d tryptophan) would increase the rate of synthesis of acute phase proteins compared with an isonitrogenous diet supplemented with alanine. METHODS: In oedematous malnourished children, a primed continuous infusion of 3H2-leucine was used to determine the in vivo synthesis rates of a1-antirypsin (a1-at), an acute phase protein, when they were infected (Study 1) and after clearing of infection (Study 2). RESULTS: There was effect of aromatic amino acid supplementation on the rate of synthesis or concentration of a1-at. CONCLUSION: Supplementation of the diet of oedematous malnourished children with aromatic amino acids did not enhance the immune response as determined by the in vivo synthesis of a1-at. (AU)

Acute-phase protein response to infection in severe malnutrition

It is not known whether malnourished infant can mount a comprehensive acute-phase protein (APP) response and, if so, whether this is achieved by increasing APP synthesis rates. To address these issues, we measured 1) the plasma concentrations of five APPs (C-reactive protein, O1-acid glycoprotein, O1-antitrypsin, haptoglobin, and fibrinogen) and 2) the synthesis rates of three APPs (O1-antitrypsin, haptoglobin, and fibrinogen) using a constant intragastric infusion of [2H3] leucine in nine infected marasmic children at 2 days postadmission (study 1), 9 days postadmission when infections had cleared (study 2), and 59 days postadmission at recovery (study 3). Except for fibrinogen, the plasma concentrations of all APPs were higher in study 1 than in studies 2 and 3. Although the rate of synthesis of haptoglobin was significantly greater in study 1 than in study 2, the rates of fibrinogen and O1-antitrypsin synthesis were similar in all three studies. These results show that 1) severely malnourished children can mount an APP response to infection which does not include fibrinogen and 2) the APP response is accomplished through different mechanisms. (AU)

Albumin kinetics in edematous and nonedematous protein-energy malnourished children

The kinetic changes responsible for decreased plasma albumin and the relation between plasma albumin and the edema of protein-energy malnutrition (PEM) were investigated by measuring the plasma concentration, fractional (FSR) and intravascular absolute (ASR) synthesis rates of albumin in seven edematous and seven nonedematous children with PEM by using constant intragastric infusions of [2H3] leucine. Studies were done 2 d postadmission (study 1), 8 d postadmission (study 2), and at recovery (study 3). In study 1 there were no significant differences in plasma albumin concentrations in nonedematous and edematous children. In both groups, albumin concentrations but not FSRs were lower in studies 1 and 2 than in study 3. The ASR was lower only in edematous patients. These results suggest that repletion of the albumin pool of children with PEM is not mediated by changes in the FSR, and the edema of malnutrition is not solely due to hypoalbuminemia. (AU)

Comparison of 15N-labelled glycine, aspartate, valine and leucine for measurement of whole-body protein turnover

Whole-body protein turnover was measured in rats by constant infusion of 15N-labelled glycine, aspartate, valine and leucine and measuring the enrichment of hepatic and renal urea and ammonia nitrogen. The values obtained with [15N] glycine were comparable with values reported with methods based on different assumptions. [15N] Aspartate gave rise to an increased enrichment of urea and ammonia and hence to lower protein-turnover rates. [15N] Valine and [15N] leucine gave low enrichments of nitrogenous end products and hence to high protein-turnover rates. All 15N-labelled amino acids are not equally suitable for measuring whole-body protein turnover by the end-product method. The relative amounts of 15N going to the end products can be prodicted from the known individual metabolism of aspartate and the branched-chain amino acids (AU)

Total protein synthesis in elderly people: a comparison of results with [15N]glycine and [14C]leucine

Total body protein turnover was studied in six elderly patients. During the study they were fed by continuous infusion of a liquid formula through a nasogastric tube. L-[1-1+C] leucine and [15N]-glycine were infused at a constant rate for 30 h. The labelled glycine was infused into the intragastric line; the labelled leucine was given either by this route of intravenously. The specific radioactivity of free leucine in plasma and the rate of output of 14CO2 in expired air both reached a plateau at 10 h, and remained constant until the end of the infusion at 30 h. The 15N abundance in urinary urea and total N was very similar. In neither was a plateau reached by 30 h but in four out of the six patients the abundance in urinary NH4+ had attained a plateau by the end of the infusion. Flux rates and rates of protein synthesis were calculated in four ways: (A) from the specific radioactivity of plasma leucine at plateau; (B) from the proportion of dose excreted as 1+CO2 at plateau; (C) from the final rates of 15N excretion in urea or total urinary N; (D) from the final or plateau rates of 15N excretion in urinary NH4+. On average, the estimates of synthesis rate obtained by methods B and C agreed closely; those given by methods A and D were lower.(AU)

Fat metabolism in protein malnutrition

The aim of this work was to make an assessment of the role of impaired lipoprotein secretion from the liver in the pathogenesis of the fatty liver caused by protein malnutrition in infants. The only evidence for this role prior to the study was that serum lipid levels were lower than normal in patients with fatty liver. The proposed method for measuring the incorporation of amino acids into the lipoproteins of children with fatty liver was used first with the rat as a model. It was found, in the development of such a model, that there are great variations in the level of liver fat induced by protein depletion in the rat. The variations depend on the age and nutritional state of the animal at the time of introducing the low-protein diet, and depend on the calorie intake while thay are on the diet. It was found that there were always measurable increases in the liver fat content when 70-gram rats were fed a 6 percent casein diet for 7 to 10 days. The use of this model with either single-injection or constant-infusion techniques showed that the incorporation of labelled amino acids into the serum lipoproteins was reduced. The greatest reduction was in the VLDL fraction of the low-density lipoproteins. There was no evidence for any significant contribution to the fatty liver from increased lipogenesis at the time when the defect in lipoprotein synthesis was apparent. The incorporation of methionine-S35 into the low-density lipoproteins of malnourished children was measured; although the changes were not consistent throughout the group studied, there was some evidence that the incorporation of the amino acid into lipoproteins was less when the children were malnourished than when they had recovered. Some modification in the design of future experiments of this type are discussed. Routine measurements of serum triglycerides in the patients during treatment showed that there are some differences between the pattern seen here and that reported elsewhere. The patients had very low triglyceride levels after recovery. These low levels were found to be due to the high fat content of the diet which the patients received during treatment. The changes in serum triglycerides induced by changing the fat content of the diet were found to be more rapid and to be relatively greater than any changes previously reported for adults. No explanation for this is given at present. The unusual patterns for serum triglycerides found during treatment of the malnourished patients with a low-fat diet appeared at first to be inconsistent with reduced synthesis of lipoprotein being associated with the fatty liver; other changes in fat metabolism concurrent with such a defect, however, could account for the unusual patterns.(AU)

Teratogenicity of hypoglycin-A: some morphological and biochemical aspects

Hypoglycin-A is a toxic, non-proteinogenic amino acid of considerable biochemical interest. It is obtained fron the fruit of Blighia sapida K., and is the causative factor of the Jamaican "vomiting sickness". The toxicity of hypoglycin-A is attributed to the formation of a metabolic methylenecycclopropaneacetic acid which inhibits the oxidation of long-chain fatty acids. Hypoglycin-A induced in pregnant rats a significantly high incidence of congenital abnormalities and reabsorption. It did not reduce the fertility in mice, malformations were absent and only a small increase in reabsorption sites was observed after the adminstration of large doses. Hypoglycin-A administered to pregnant rabbits resulted in a high incidence of foetal reabsorption and overall stunting. Injected into the yolk sac of 24 and 48 hour chick embryos, hypoglycin-A was not teratogenic. Leucine, administered to pregnant rats simutaneously with hypoglycin-A, afforded no protection against the teratogenic action of hypoglycin-A. Leucine was shown to be highly teratogenic and exaggerated the teratogenicity of riboflavin and hypoglycin-A to pregnant rats the occurrence of congenital abnormalities. Inhibition of long-chain fatty acid oxidation may represent a basic cellular mechanism involved in the teratogenicity of hypoglycin-A, because of its influence on oxidative phosphorylation and the electron transport system. Reversal of the hypoglycin-induced teratogenic effects by riboflavin, suggests that inhibition of the acyl dehydrogenase flavin-dependent-oxidation reaction, occurring during the degradation of fatty acids, is the site of action of hypoglycin-A (AU)

Amino acid imbalance and embroyonic development - abstract

The effects of the essential amino acid leucine on maternal reproductive capacity and embryonic development in the rat were investigated. Leucine, 15 mg/kg body weight, was administered intraperitoneally to two groups of pregnant rats from the first through the sixth day, and from the sixth through the ninth day of gestation respectively. Control animals received physiological saline over the same gestational period. A high incidence and a wide spectrum of congenital abnormalities were induced in the leucine-treated rats; the incidence of embryonic death and foetal resorption was also significantly increased following treatment with leucine (P < 0.001). Skeletal malformations were present in a number of instances, but no microscopic changes were observed in the foetal organs studied. The embryopathic activity ofleucine may be due to an imbalance in the "amino acid pool" which is available for protein synthesis during embryonic development(AU)

Some biological observations of hypoglycin A in presence of leucine - abstract

The present work was carried out to investigate the effect of leucine on the biological activity of hypoglycin A. Leucine-free hypoglycin A, prepared from the ackee (Blighia sapida) seeds, has been shown to cause inhibition of the growth of broad bean radicles. When supplied simultaneously, leucine had no effect on the degree of inhibition produced by hypoglycin A even when the leucine concentration was four times that of hypoglycin A. Although the acceped structure of hypoglycin A bears a relationship to that of leucine, yet leucine does not antagonise the inhibitory action of hypoglycin A. When injected intraperitoneally into rats, fasted for 48 hours to ensure complete depletion of their liver glycogen, hypoglycin A induced hypoglycemia. This hypoglycemia was potentiated by leucine when administered one hour before hypoglycin A. These findings indicate that the hypooglycemia induced by hypoglycin A is not a result of the exhaustion of the liver glycogen as was suggested by Patrick (1954). They also indicate that the liver is not the principal site of action as thought by Chen et al. (1957).(AU)

Stimulation of insulin secretion in vitro by essential aminoacids

Leucine was the only essential aminoacid to stimulate insulin release from rabbit pancreas in vitri in the absence of extracellular glucose. In the presence of 1.5 mg glucose, per ml leucine, arginine, lysine and isoleucine were effective stimuli of insulin release (Summary)

The foetal toxicity of leucine in the rat

The amino acid leucine, administered to pregnant rats during early gestation, induced a high incidence of multiple congenital abnormalities and foetal resorptions. These adverse effects may be accounted for by an imbalance in the amino acid pool, which is available for protein synthesis during embryonic development (AU)