AJP - Endocrinology and Metabolism, Vol 270, Issue 2 E209-E214, Copyright © 1996 by American Physiological Society

ARTICLES

Plasma methionine and cysteine kinetics in response to an intravenous glutathione infusion in adult humans

N. K. Fukagawa, A. M. Ajami and V. R. Young
Clinical Research Center, Rockefeller University, New York, New York 10021, USA.

Glutathione (GSH), a tripeptide (gamma-glutamyl-cysteinyl-glycine), is thought to be both a storage and a transport form of cysteine (Cys). In a previous study (T. Hiramatsu, N.K. Fukagawa, J.S. Marchini, J. Cortiella, Y.-M. Yu, T.E. Chapman, and V.R. Young. Am. J. Clin. Nutr. 60: 525-533, 1994), the direct tracer-derived estimate of Cys flux was considerably higher than that predicted from estimates of protein turnover. To further examine the components of plasma Cys flux, seven normal-weight healthy adult men and women (26 +/- 2 yr) received stable isotope tracer infusions of L-[methyl-2H3;1-13C]methionine, L-[3,3-2H2]cysteine, and L-[methyl-2H3]leucine for 460 min. After a 3-h baseline period, GSH was administered at approximately 32 mumol.kg-1.h-1 until the end of the study. Expired breath and blood samples were obtained at timed intervals and analyzed for isotope enrichment using mass spectrometry. Leucine, alpha-ketoisocaproate, and methionine (carboxyl carbon, methyl moiety, remethylation, and transsulfuration) turnover were reduced during GSH administration (P < 0.01). In the final hour of GSH administration, Cys flux increased by 61% from 55.1 +/- 1.7 to 88.7 +/- 5.2 mumol.kg-1.h-1 (P < 0.01), which was essentially equivalent to the rate of exogenous GSH infusion. These data suggest that GSH breakdown accounts for approximately 50% of tracer-derived Cys flux basally and for all of the increase in measured Cys turnover during exogenous GSH infusion.

This article has been cited by other articles:

				D. P. Jones Radical-free biology of oxidative stress Am J Physiol Cell Physiol, October 1, 2008; 295(4): C849 - C868. [Abstract] [Full Text] [PDF]

				B. Rakotoambinina, L. Marks, A. M. Badran, F. Igliki, F. Thuillier, P. Crenn, B. Messing, and D. Darmaun Taurine kinetics assessed using [1,2-13C2]taurine in healthy adult humans Am J Physiol Endocrinol Metab, August 1, 2004; 287(2): E255 - E262. [Abstract] [Full Text] [PDF]

				G. Garibotto, A. Sofia, S. Saffioti, R. Russo, G. Deferrari, D. Rossi, D. Verzola, M. T. Gandolfo, and M. R. Sala Interorgan exchange of aminothiols in humans Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E757 - E763. [Abstract] [Full Text] [PDF]

				C. Hou, L. J. Wykes, and L. J. Hoffer Urinary Sulfur Excretion and the Nitrogen/Sulfur Balance Ratio Reveal Nonprotein Sulfur Amino Acid Retention in Piglets J. Nutr., March 1, 2003; 133(3): 766 - 772. [Abstract] [Full Text] [PDF]

				M. J. Hamadeh and L. J. Hoffer Effect of protein restriction on sulfur amino acid catabolism in insulin-dependent diabetes mellitus Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E382 - E389. [Abstract] [Full Text] [PDF]

				M. J. Hamadeh, A. Schiffrin, and L. J. Hoffer Sulfate production depicts fed-state adaptation to protein restriction in humans Am J Physiol Endocrinol Metab, August 1, 2001; 281(2): E341 - E348. [Abstract] [Full Text] [PDF]

				M. J. Hamadeh and L. J. Hoffer Use of sulfate production as a measure of short-term sulfur amino acid catabolism in humans Am J Physiol Endocrinol Metab, June 1, 2001; 280(6): E857 - E866. [Abstract] [Full Text] [PDF]

				M. J. MacCoss, N. K. Fukagawa, and D. E. Matthews Measurement of intracellular sulfur amino acid metabolism in humans Am J Physiol Endocrinol Metab, June 1, 2001; 280(6): E947 - E955. [Abstract] [Full Text] [PDF]

				S. P Stabler, R. L Morton, S. L Winski, R. H Allen, and C. W White Effects of parenteral cysteine and glutathione feeding in a baboon model of severe prematurity Am. J. Clinical Nutrition, December 1, 2000; 72(6): 1548 - 1557. [Abstract] [Full Text] [PDF]

				T. Malmezat, D. Breuille, C. Pouyet, C. Buffiere, P. Denis, P. P. Mirand, and C. Obled Methionine transsulfuration is increased during sepsis in rats Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1391 - E1397. [Abstract] [Full Text] [PDF]

				N. K Fukagawa, J. M Martin, A. Wurthmann, A. H Prue, D. Ebenstein, and B. O'Rourke Sex-related differences in methionine metabolism and plasma homocysteine concentrations Am. J. Clinical Nutrition, July 1, 2000; 72(1): 22 - 29. [Abstract] [Full Text] [PDF]

				P. J. Reeds Dispensable and Indispensable Amino Acids for Humans J. Nutr., July 1, 2000; 130(7): 1835S - 1840. [Abstract] [Full Text]

				C. C. Metges, Y.-M. Yu, W. Cai, X.-M. Lu, S. Wong, M. M. Regan, A. Ajami, and V. R. Young Oxoproline kinetics and oxoproline urinary excretion during glycine- or sulfur amino acid-free diets in humans Am J Physiol Endocrinol Metab, May 1, 2000; 278(5): E868 - E876. [Abstract] [Full Text] [PDF]

				T. Malmezat, D. Breuillé, P. Capitan, P. P. Mirand, and C. Obled Glutathione Turnover Is Increased during the Acute Phase of Sepsis in Rats J. Nutr., May 1, 2000; 130(5): 1239 - 1246. [Abstract] [Full Text]

				C. A Raguso, M. M Regan, and V. R Young Cysteine kinetics and oxidation at different intakes of methionine and cystine in young adults1 Am. J. Clinical Nutrition, February 1, 2000; 71(2): 491 - 499. [Abstract] [Full Text] [PDF]

				N. K. Fukagawa, E. Hercules, and A. M. Ajami L-2-[13C]oxothiazolidine-4-carboxylic acid: a probe for precursor mobilization for glutathione synthesis Am J Physiol Endocrinol Metab, January 1, 2000; 278(1): E171 - E176. [Abstract] [Full Text] [PDF]

				C. C. Metges, Y.-M. Yu, W. Cai, X.-M. Lu, S. Wong, A. M. Ajami, and V. R. Young Plasma L-5-Oxoproline Carbon and Nitrogen Kinetics in Healthy Young Adults J. Nutr., November 1, 1999; 129(11): 1998 - 2004. [Abstract] [Full Text]

				J. Lyons, A. Rauh-Pfeiffer, Y. M. Yu, X.-M. Lu, D. Zurakowski, R. G. Tompkins, A. M. Ajami, V. R. Young, and L. Castillo Blood glutathione synthesis rates in healthy adults receiving a sulfur amino acid-free diet PNAS, May 9, 2000; 97(10): 5071 - 5076. [Abstract] [Full Text] [PDF]