Cys/CySS and GSH/GSSG redox states in human plasma undergo diurnal variation with an increased magnitude of variation in Cys/CySS redox state in older persons. This variation could alter sensitivity to oxidative stress over a course of hours.

BackgroundCysteine (Cys) and its disulfide, cystine (CySS) represent the major extracellular thiol/disulfide redox control system. The redox potential (Eh) of Cys/CySS is centered at approximately −80 mV in the plasma of healthy adults, and oxidation of Eh Cys/CySS is implicated in inflammation associated with various diseases.Methodology/Principal FindingsThe purpose of the present study was to determine whether oxidized Eh Cys/CySS is a determinant of interleukin (IL)-1β levels. Results showed a 1.7-fold increase in secreted pro-IL-1β levels in U937 monocytes exposed to oxidized Eh Cys/CySS (−46 mV), compared to controls exposed to a physiological Eh of −80 mV (P<0.01). In LPS-challenged mice, preservation of plasma Eh Cys/CySS from oxidation by dietary sulfur amino acid (SAA) supplementation, was associated with a 1.6-fold decrease in plasma IL-1β compared to control mice fed an isonitrogenous SAA-adequate diet (P<0.01). Analysis of Eh Cys/CySS and IL-1β in human plasma revealed a significant positive association between oxidized Eh Cys/CySS and IL-1β after controlling for age, gender, and BMI (P<0.001).Conclusions/SignificanceThese data show that oxidized extracellular Eh Cys/CySS is a determinant of IL-1β levels, and suggest that strategies to preserve Eh Cys/CySS may represent a means to control IL-1β in inflammatory disease states.

Objective-Oxidation of plasma cysteine/cystine (Cys/CySS) redox potential (E h CySS) has been associated with risk factors for cardiovascular disease in humans. Cys and CySS are derived from dietary sulfur amino acids (SAA), but the specific effects of SAA depletion and repletion on Cys/ CySS redox indices are unknown. The present study examined the effect of dietary SAA intake level on free Cys, free CySS and E h CySS in human plasma under fasting conditions.Research Methods and Procedures-Healthy individuals aged 18-36 y (n=13) were equilibrated to foods providing the RDA for SAA and then fed chemically defined diets without SAA (0 mg·kg −1 ·d −1 ; n=13) followed by SAA at levels approximating the mean (56 mg·kg −1 ·d −1 ; n=8) or 99th percentile (117 mg·kg −1 ·d −1 ; n=5) intake levels of Americans. Fasting plasma samples were collected daily during 4-d study periods and analyzed for free Cys, free CySS and the E h CySS.Results-The SAA-free diet significantly (p<0.05) decreased plasma free Cys concentrations and oxidized E h CySS values after 4 days of SAA depletion. With SAA repletion at 56 mg·kg −1 ·d − 1 , plasma free Cys increased significantly and values for E h CySS became more reducing. Administration of a diet providing a higher dose of SAA (117 mg·kg −1 ·d −1 ) resulted in a significantly higher level of free Cys and a more reducing E h CySS.Conclusions-These results show that free Cys and Cys/CySS redox potential (E h CySS) in fasting plasma are affected by dietary SAA intake level in humans. Significant changes occur slowly over 4 days with insufficient SAA intake, but rapidly (after 1 day) with repletion.

DP. Individual variation in macronutrient regulation measured by proton magnetic resonance spectroscopy of human plasma. Am J Physiol Regul Integr Comp Physiol 297: R202-R209, 2009. First published May 20, 2009 doi:10.1152/ajpregu.90757.2008.-Proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy of plasma provides a global metabolic profiling method that shows promise for clinical diagnostics. However, cross-sectional studies are complicated by a lack of understanding of intraindividual variation, and this limits experimental design and interpretation of data. The present study determined the diurnal variation detected by 1 H NMR spectroscopy of human plasma. Data reduction methods revealed three time-of-day metabolic patterns, which were associated with morning, afternoon, and night. Major discriminatory regions for these time-of-day patterns included the various kinds of lipid signals , and the region between 3 and 4 ppm heavily overlapped with amino acids that had ␣-CH and ␣-CH2. The phasing and duration of time-of-day patterns were variable among individuals, apparently because of individual difference in food processing/digestion and absorption and clearance of macronutrient energy sources (fat, protein, carbohydrate). The times of day that were most consistent among individuals, and therefore most useful for cross-sectional studies, were fasting morning (0830 -0930), postprandial afternoon (1430 -1630), and nighttime samples (0430 -0530). Importantly, the integrated picture of metabolism provided by 1 H-NMR spectroscopy of plasma suggests that this approach is suitable to study complex regulatory processes, including eating patterns/eating disorders, upper gastrointestinal functions (gastric emptying, pancreatic, biliary functions), and absorption/clearance of macronutrients. Hence, 1 H-NMR spectroscopy of plasma could provide a global metabolic tolerance test to assess complex processes involved in disease, including eating disorders and the range of physiological processes causing dysregulation of energy homeostasis. metabolomics; diurnal variation; eating disorders; gastrointestinal regulation GLOBAL METABOLIC PROFILING coupled with bioinformatic methods offers an approach to study the integration of macronutrient energy metabolism and can be useful to detect disease, toxicity, and nutritional deficiency (11,23,30,36). A variety of metabolic profiling methods are available, including gas chromatography-mass spectrometry, liquid chromatographymass spectrometry, and NMR spectroscopy (10,31,39). In view of its capability to handle multiple specimens in a high-throughput, semiautomated system, 1 H-NMR may offer unique insight into the in vivo metabolism of macronutrients (1, 2, 9). Dysfunction in macronutrient metabolism, i.e., carbohydrate, fat, protein, and alcohol, is relevant to obesity, metabolic syndrome, diabetes, cardiovascular disease and other common pathological conditions (19,25).Pioneering studies by Nicholson and coworkers (3, 24, 27, 35) established the utility of 1 H NMR spectroscopy f...