Varied food intake, disease and genetic differences result in complex diet-health interactions. In principle, information-rich metabolic analyses combined with bioinformatic tools provide an approach to explore these interactions. This project is a feasibility study of the use of high-resolution 1H-NMR to study metabolic perturbations induced by deficiency in sulfur amino acids (SAA). In cell culture, sulfur amino acid (SAA) deficiency results in substantial oxidation of glutathione (GSH) redox state. Because GSH redox affects central homeostatic and cell defense mechanisms, redox changes in vivo due to SAA deficiency could induce complex physiologic effects that are not easily predictable by more traditional metabolic analyses. We will 1) test the hypothesis that deficient dietary intake of SAA in humans results in oxidation of GSH/GSSG redox and 2) determine whether 1H-NMR of blood and urine detects metabolic changes due to SAA deficiency. Studies will be performed on 12 healthy individuals (6 males, 6 females) in the Emory General Clinical Research Center (GCRC) using a crossover design (replete, deficient, replete). Kinetic and balance studies will establish the time course and magnitude of changes in SAA and metabolites in blood and urine in response to SAA intake. Plasma GSH/GSSG and cysteine/cystine redox will be measured to determine whether variation in intake of SAA affects steady-state thiol-disulfide redox state. 1H-NMR spectra of blood and urine samples will be used to determine whether metabolic changes unrelated to the direct SAA metabolites can be detected in association with variation in SAA intake. The results will show whether variation in SAA intake is likely to affect health risks associated with thiol-disulfide redox and oxidative stress. Furthermore, because NMR analysis of biofluids can be performed with a high throughput (e.g., 300 samples/day with a flow cell), results will show whether this approach could be useful for nutritional assessment of complex metabolic effects of SAA intake.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
1R03DK066008-01
Application #
6710374
Study Section
Special Emphasis Panel (ZDK1-GRB-9 (O4))
Program Officer
Miles, Carolyn
Project Start
2004-03-01
Project End
2006-02-28
Budget Start
2004-03-01
Budget End
2005-02-28
Support Year
1
Fiscal Year
2004
Total Cost
$153,000
Indirect Cost
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Park, Youngja; Lee, Kichun; Ziegler, Thomas R et al. (2013) Multifractal analysis for nutritional assessment. PLoS One 8:e69000
Park, Youngja; Zhao, Tiejun; Miller, Nana Gletsu et al. (2012) Sulfur amino acid-free diet results in increased glutamate in human midbrain: a pilot magnetic resonance spectroscopic study. Nutrition 28:235-41
Jones, Dean P; Park, Youngja; Gletsu-Miller, Nana et al. (2011) Dietary sulfur amino acid effects on fasting plasma cysteine/cystine redox potential in humans. Nutrition 27:199-205
Park, Youngja; Jones, Dean P; Ziegler, Thomas R et al. (2011) Metabolic effects of albumin therapy in acute lung injury measured by proton nuclear magnetic resonance spectroscopy of plasma: a pilot study. Crit Care Med 39:2308-13
Park, Youngja; Le, Ngoc-Anh; Yu, Tianwei et al. (2011) A sulfur amino acid-free meal increases plasma lipids in humans. J Nutr 141:1424-31
Mannery, Yanci O; Ziegler, Thomas R; Park, Youngja et al. (2010) Acetaminophen elimination half-life in humans is unaffected by short-term consumption of sulfur amino acid-free diet. J Pharmacol Exp Ther 333:948-53
Mannery, Yanci O; Ziegler, Thomas R; Park, Youngja et al. (2010) Oxidation of plasma cysteine/cystine and GSH/GSSG redox potentials by acetaminophen and sulfur amino acid insufficiency in humans. J Pharmacol Exp Ther 333:939-47
Jung, Yoon Young; Park, Youngja; Jones, Dean P et al. (2010) Self-similarity in NMR Spectra: An Application in Assessing the Level of Cysteine. J Data Sci 8:1-19
Johnson, Jennifer M; Yu, Tianwei; Strobel, Frederick H et al. (2010) A practical approach to detect unique metabolic patterns for personalized medicine. Analyst 135:2864-70
Park, Youngja; Ziegler, Thomas R; Gletsu-Miller, Nana et al. (2010) Postprandial cysteine/cystine redox potential in human plasma varies with meal content of sulfur amino acids. J Nutr 140:760-5

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