GLUTATHIONE HOMEOSTASIS & OXIDANT DAMAGE IN KWASHIORKOR

Summary

Principal Investigator: F Jahoor
Affiliation: Texas Medical Center
Country: USA
Abstract: Whereas the marasmus syndrome of severe protein-energy- malnutrition (PEM) is simple to treat and has a low mortality rate, the kwashiokor (K) and marasmic-kwashiorkor (MK) syndromes are difficult to treat and have high mortality rates because they have more greatly impaired immune and organ functions. Based on evidence that the concentrations of glutathione (GSH), a major anti-oxidant, are lower in K and MK, but not in marasmus, it has been proposed that oxidants cause cell damage in the organs and tissues of children with K and MK because of impaired antioxidant capacity. However, the extent to which antioxidant capacity is actually impaired, the cause of such an impairment, and the relationships to oxidant damage and to the degree of immunological and patho-physiological derangements of K and MK have not been determined. The research proposed addresses the following hypotheses: i) that in the K and MK syndromes of PEM there is an increase in oxidative damage because of compromised GSH synthesis, ii) that the slower GSH synthesis rate is secondary to decreased availability of its precursors cysteine and glycine, iii) that the shortage of these GSH precursors is due to both decreased de novo synthesis and slower whole body protein breakdown rate, iv) that dietary supplementation with cysteine and glycine during early nutritional rehabilitation will permit faster normalization of GSH synthesis and supply thereby reducing oxidative damage, v) that faster normalization of GSH synthesis and concentration will be associated with parallel improvements in immune function and rates of loss of edema and liver fat. Using biochemical and stable isotope tracer methods, these hypotheses will be tested in 6-18 mo old infants with PEM. The first experimental protocol will determine differences in 1) the rates of synthesis of erythrocyte GSH, cysteine and glycine, 2) whole body protein breakdown rate, 3) the plasma concentrations of lipid hydroperoxides and meta-and ortho- tyrosine, indicators of oxidative damage, between infants with marasmus, K and MK at admission (study 1), after metabolic stabilization (study 2) and at recovery (study 3). The second experimental protocol will determine the effect of cysteine and glycine supplementation on these outcome variables and on the relationships between GSH synthesis and concentration, lymphocyte function and the rate of loss of edema and liver fat in children with K and MK. The data obtained will provide insight into the the extent to which anti-oxidant capacity is impaired in K and MK, its relationship to oxidant damage and whether therapeutic approaches aimed to replenish antioxidant capacity will accelerate clinical and metabolic recovery from PEM.
Funding Period: 2000-09-01 - 2003-04-30
more information: NIH RePORT

Top Publications

  1. ncbi Sulfur amino acid metabolism in children with severe childhood undernutrition: cysteine kinetics
    Farook Jahoor
    US Department of Agriculture, Agricultural Research Service, Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030 2600, USA
    Am J Clin Nutr 84:1393-9. 2006
  2. ncbi Sulfur amino acid metabolism in children with severe childhood undernutrition: methionine kinetics
    Farook Jahoor
    US Department of Agriculture, Agricultural Research Service, Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030 2600, USA
    Am J Clin Nutr 84:1400-5. 2006
  3. ncbi Relation between liver fat content and the rate of VLDL apolipoprotein B-100 synthesis in children with protein-energy malnutrition
    Asha Badaloo
    Tropical Metabolism Research Unit, University Hospital of the West Indies, University of the West Indies, Mona, Kingston, Jamaica
    Am J Clin Nutr 81:1126-32. 2005
  4. ncbi Protein kinetic differences between children with edematous and nonedematous severe childhood undernutrition in the fed and postabsorptive states
    Farook Jahoor
    US Department of Agriculture Agricultural Research Service, Children s Nutrition Research Center, Houston, TX 77030 2600, USA
    Am J Clin Nutr 82:792-800. 2005
  5. ncbi Lipid kinetic differences between children with kwashiorkor and those with marasmus
    Asha V Badaloo
    Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston, Jamaica
    Am J Clin Nutr 83:1283-8. 2006
  6. ncbi Glycine production in severe childhood undernutrition
    Farook Jahoor
    US Department of Agriculture, Agricultural Research Service, Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030 2600, USA
    Am J Clin Nutr 84:143-9. 2006
  7. ncbi Arginine flux and intravascular nitric oxide synthesis in severe childhood undernutrition
    Farook Jahoor
    US Department of Agriculture Agricultural Research Service, Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030 2600, USA
    Am J Clin Nutr 86:1024-31. 2007

Scientific Experts

  • F Jahoor
  • Asha V Badaloo
  • Marvin Reid
  • Terrence Forrester
  • Asha Badaloo
  • Deanne Soares

Detail Information

Publications7

  1. ncbi Sulfur amino acid metabolism in children with severe childhood undernutrition: cysteine kinetics
    Farook Jahoor
    US Department of Agriculture, Agricultural Research Service, Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030 2600, USA
    Am J Clin Nutr 84:1393-9. 2006
    ..We propose that these lower cysteine concentrations are due to reduced production secondary to slower de novo synthesis plus decreased release from protein breakdown...
  2. ncbi Sulfur amino acid metabolism in children with severe childhood undernutrition: methionine kinetics
    Farook Jahoor
    US Department of Agriculture, Agricultural Research Service, Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030 2600, USA
    Am J Clin Nutr 84:1400-5. 2006
    ..We propose that methionine production and metabolism will be slower in children with edematous SCU than in those with nonedematous SCU...
  3. ncbi Relation between liver fat content and the rate of VLDL apolipoprotein B-100 synthesis in children with protein-energy malnutrition
    Asha Badaloo
    Tropical Metabolism Research Unit, University Hospital of the West Indies, University of the West Indies, Mona, Kingston, Jamaica
    Am J Clin Nutr 81:1126-32. 2005
    ..Thus, fatty infiltration of the liver in PEM is not due to a reduction in the synthesis of VLDL-apo B-100...
  4. ncbi Protein kinetic differences between children with edematous and nonedematous severe childhood undernutrition in the fed and postabsorptive states
    Farook Jahoor
    US Department of Agriculture Agricultural Research Service, Children s Nutrition Research Center, Houston, TX 77030 2600, USA
    Am J Clin Nutr 82:792-800. 2005
    ..It was hypothesized that, in edematous but not nonedematous SCU, impaired protein breakdown leading to inadequate amino acids for maintenance of important organ systems was a factor...
  5. ncbi Lipid kinetic differences between children with kwashiorkor and those with marasmus
    Asha V Badaloo
    Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston, Jamaica
    Am J Clin Nutr 83:1283-8. 2006
    ..However, this hypothesis has not been tested...
  6. ncbi Glycine production in severe childhood undernutrition
    Farook Jahoor
    US Department of Agriculture, Agricultural Research Service, Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030 2600, USA
    Am J Clin Nutr 84:143-9. 2006
    ..This is especially true under unique circumstances, such as when the availability of labile nitrogen for dispensable amino acid synthesis is reduced, as in severe childhood undernutrition...
  7. ncbi Arginine flux and intravascular nitric oxide synthesis in severe childhood undernutrition
    Farook Jahoor
    US Department of Agriculture Agricultural Research Service, Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030 2600, USA
    Am J Clin Nutr 86:1024-31. 2007
    ....