ISSN:0731-5724    

DOI:10.1080/07315724.1986.10738082

出版商:Routledge    

年代:1986

数据来源: Taylor

ISSN:0731-5724    

DOI:10.1080/07315724.1986.10720117

出版商:Routledge    

年代:1986

数据来源: Taylor

摘要:

Protein synthesis depends on a complete complement of precursor amino acids, specific acetylating enzymes, tRNA, and so forth. It has been related to metabolism of individual amino acids, eg, valine and leucine; however, the relation of protein synthesis to the ambient concentrations of amino acids in the intracellular and extracellular pools has not been defined. Using the viable, isolated granulocyte (leukocyte) as an in vitro cell model, protein synthesis (incorporation of 4,5-3H-leucine) has been related to simultaneous amino acid concentrations in the cell and plasma by multiple regression analysis. Fifty-five normal neonates and 30 normal adults were studied. Protein synthesis was higher in the infants than in the adults (3,527 vs 2,685 pmole/hr/mg DNA). The intracellular concentrations of most amino acids were higher than their concentrations in plasma, except for valine and citrulline, which were lower. The“aminograms”in the two pools also were very different. Forty-four percent of the variance (R2) in protein synthesis was accounted for by the intracellular concentrations of leucine, glycine, alanine, and taurine in neonates and 45% by a combination of threonine, valine, methionine, and histidine in adults. The intracellular concentrations of each of these predictor amino acids in adults were, in turn, related to different combinations of the plasma concentrations of threonine, phenylalanine, tryptophan, isoleucine, histidine, citrulline, ornithine, arginine, and glycine. Thus, it is possible to identify sets of intracellular amino acids that predict the level of protein synthesis and to delineate combinations of plasma amino acids whose levels account for a significant portion of the variance in the intracellular predictor amino acids in normal human infants and adults.

ISSN:0731-5724    

DOI:10.1080/07315724.1986.10720118

出版商:Routledge    

年代:1986

数据来源: Taylor

ISSN:0731-5724    

DOI:10.1080/07315724.1986.10720119

出版商:Routledge    

年代:1986

数据来源: Taylor

摘要:

Twenty-one children and 23 adults receiving long-term total parenteral nutrition (TPN) for 27 +/−23 (SD) months were investigated to determine if they were taurine-deficient because the TPN solutions were taurine-free. The fasting plasma taurine level was reduced in the children to 26 + 13 mumol/liter vs the control 57 +/−16 mumol/liter (P greater than 0.001). The plasma taurine level was significantly reduced in those adults who absorbed less than 25% of their nutritional needs from their diet. Electroretinograms were abnormal in each of eight children who were examined; isolated cone and rod implicit times were both significantly delayed. Electroretinograms were not abnormal in those adults with low plasma taurine levels. Taurine was added to the TPN solutions of four children, and the plasma taurine level became normal in each of them. Electroretinograms of three of these children became normal. One year after discontinuing intervenous taurine supplementation, the plasma taurine level became abnormal in two of three children. These observations indicate that children, and possibly adults, receiving long-term TPN have a nutritional requirement for taurine.

ISSN:0731-5724    

DOI:10.1080/07315724.1986.10720120

出版商:Routledge    

年代:1986

数据来源: Taylor

摘要:

Glutathione functions in catalysis, metabolism, transport, and reductive processes and in protection of cells by destruction of free radicals, reactive oxygen intermediates, and other toxic compounds of endogenous and exogenous origin. It also functions as a storage and transport form of cysteine. Depletion of glutathione (effectively accomplished by inhibition of its synthesis) increases sensitivity to radiation and to certain toxic compounds and is of value in combination with radiation therapy or chemotherapy in situations in which cell selectivity can be achieved. Increased cellular levels of glutathione protect cells against radiation and certain toxic compounds. Glutathione levels can be increased by administration of cysteine or of glutathione, but these approaches are not entirely satisfactory. Cellular glutathione levels can be increased by supplying substrate for gamma-glutamylcysteine synthetase or for glutathione synthetase. L-2-Oxothiazolidine-4-carboxylate is well transported into many cells and is converted by 5-oxoprolinase to cysteine, a substrate of gamma-glutamylcysteine synthetase. gamma-Glutamylcysteine and related compounds are effectively transported, especially into renal cells, thus providing substrate for glutathione synthetase; higher than normal levels of glutathione can be achieved because this enzyme is not significantly inhibited by glutathione, whereas gamma-glutamylcysteine synthetase is feedback-inhibited. Derivatives of glutathione that are effectively transported into cells (glutathione itself is not) offer another means of increasing glutathione levels. The monoethyl ester of glutathione (in which the glycine carboxyl group is esterified) is well transported in vivo into liver and kidney and into cultured fibroblasts and lymphoid cells. Glutathione levels much higher than usual can be obtained by this procedure, which protects lymphoid cells against the lethal effects of irradiation and mice against acetaminophen, and which therefore may be a relatively safe way to increase cellular resistance to radiation and certain toxic compounds.

ISSN:0731-5724    

DOI:10.1080/07315724.1986.10720121

出版商:Routledge    

年代:1986

数据来源: Taylor

摘要:

This communication presents evidence from the literature and recent experiments that describe circumstances wherein arginine may be a conditional dietary essential. Previous work has established that the synthesis of orotic acid (OA), the first pyrimidine formed in the de novo pathway of nucleic acid synthesis, becomes elevated whenever the ammonia load exceeds the capacity of the urea cycle. Under these circumstances, the common intermediate, carbamyl phosphate, leaks from the mitochondria and induces OA synthesis in the cytoplasm. This leads to increased OA excretion in the urine as pyrimidine synthesis escapes feedback control. A deficiency of urea cycle substrates such as arginine, and administration of certain drugs, ammonium salts, urease, or excess amino acids raises orotic acid excretion. Our recent experiments in rats show that OA excretion is also elevated after partial hepatectomy following galactosamine administration, exposure to carbon tetrachloride, or feeding 36% of calories as ethanol. The elevation in OA excretion was suppressed by dietary supplementation with arginine, implying that arginine is conditionally essential. Adult human male alcoholics showed elevated urinary orotic acid-to-creatinine ratios early after drinking episodes, which declined with time following abstinence. Such evidence shows that well studied hepatotoxins and surgical liver injury affect pathways of ammonia metabolism and suggests that urinary orotic acid can be an indicator of hepatotoxicity and increased needs for arginine. Arginine-deficient diets and alcohol feeding both enhance fatty deposition in the liver, which can be worsened by high fat intakes in rats. Alcoholism, various other diseases, and fasting and realimentation change orotic acid excretion. Such responses will have to be taken into account in establishing“normal values”for OA excretion.

ISSN:0731-5724    

DOI:10.1080/07315724.1986.10720122

出版商:Routledge    

年代:1986

数据来源: Taylor

摘要:

Relative deficiencies of ornithine or arginine occur in the presence of excessive ammonia, excessive lysine, growth, pregnancy, trauma, or protein deficiency and malnutrition. Ammonia excess may occur in the presence of a normal liver when amino acid mixtures lacking ornithine, arginine, or citrulline are infused; when specific amino acids such as glycine are injected; when ammonium salts, urea, or urease are injected; or when the gastrointestinal tract contains an excess of protein, urea, or NH4+, as occurs after a gastrointestinal hemorrhage. In these states, ornithine is often rate-limiting for urea cycle function. Ornithine is also rate-limiting when ammonia excess occurs in the presence of hepatic failure. In three of the inherited urea cycle disorders, ornithine insufficiency and ammonia excess also occur. These disorders are citrullinemia, argininosuccinic aciduria, and argininemia. In the presence of excessive lysine the availability of arginine is reduced and the formation of ornithine is decreased in the liver; urea synthesis is reduced, but orotic acid synthesis is increased, and orotic aciduria results as carbamyl phosphate is directed toward the pyrimidine pathway. Hereditary lysinuric protein intolerance results in ornithine depletion, hyperammonemia, and orotic acid uria. Optimal growth in several species of animals requires 0.4-1.0% arginine in the diet. Diets deficient in arginine are associated with poor wound healing as well as stunted growth. The measurement of orotic acid excretion has been a convenient indicator of insufficiency of ornithine or arginine during growth or pregnancy in animals and should prove useful in assessing the requirement for arginine after trauma. Normal human pregnancy is associated with low-grade orotic aciduria. Protein deficiency and malnutrition increase the vulnerability of the animal or child to ammonia toxicity. This is presumably due to insufficient ornithine for normal urea cycle responsiveness.

ISSN:0731-5724    

DOI:10.1080/07315724.1986.10720123

出版商:Routledge    

年代:1986

数据来源: Taylor

摘要:

Carnitine performs a critically important role in energy metabolism and is synthesized in the healthy adult predominantly in the liver and kidney. The typical well balanced American diet contains significant amounts of carnitine as well as the essential amino acids and micronutrients needed for carnitine biosynthesis. Thus carnitine is an infrequent problem in the healthy, well nourished adult population in the United States. However, carnitine can be a conditionally essential nutrient for several different types of individuals. Preterm infants require carnitine for life-sustaining metabolic processes but have a carnitine biosynthetic capability that is not fully developed. There is an increasing number of documented problems with carnitine metabolism in preterm infants not receiving an exogenous source of carnitine indicating that endogenous biosynthesis of carnitine is not adequate to meet the infant's need. Children with different forms of organic aciduria appear to have a greatly increased need for carnitine to function in the excretion of the accumulating organic acids. This need exceeds their dietary carnitine intake and carnitine biosynthetic capability. Renal patients treated with chronic hemodialysis appear to lose carnitine via the hemodialysis treatment, and this loss cannot be repleted simply by endogenous biosynthesis and dietary intake. Treatment with drugs such as valproic acid and metabolic stresses such as trauma, sepsis, organ failure, etc, can also result in a requirement for exogenous carnitine. Accurate assessment of the carnitine status of patients at risk for carnitine deficiency is fundamental to the identification of those patients who require carnitine as the result of altered metabolism.

ISSN:0731-5724    

DOI:10.1080/07315724.1986.10720124

出版商:Routledge    

年代:1986

数据来源: Taylor

摘要:

Since the discovery in 1929 that certain polyunsaturated fatty acids (PUFA) are essential for life and health, intense investigation has revealed the multiplicity of members in each of several families of PUFA, no two of which are equivalent. The quantified nutrient requirements for the essential dietary precursors of the two dominant families of PUFA have been estimated, and the general functions of these families are slowly becoming known. The PUFA are essential components of structural membrane lipids. The functions of the individual members are not yet differentiated, except as they act as precursors of synthesis of unique octadecanoid, eicosanoid, and docosanoid products of oxidation that have potent biological properties. The PUFA occur in animals and higher plants as ubiquitous and essential components of structural lipid that are in a dynamic equilibrium with the pool of dietary acyl groups. Many human diseases have been found to involve unique essential fatty acid (EFA) deficiencies or distortions of the normal equilibrium pattern. The equilibrium is influenced by the level of dietary intake or precursors, by the presence of competing essential and nonessential acyl groups, by nonoptimum intake of other essential nutrients, by hormonal effects, by drug therapy, and by other effects upon physiological condition. With the many variables already known to modulate or control the equilibrium, it should be possible with more precise understanding of each variable to shift abnormal equilibria in the direction of normalcy. This perhaps will be the next area of intensive investigation in this field of nutrition and metabolism.

ISSN:0731-5724    

DOI:10.1080/07315724.1986.10720125

出版商:Routledge    

年代:1986

数据来源: Taylor