Metabolite profile analysis reveals functional effects of 28-day vitamin b-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthymen andwomen

Journal of Nutrition

Volumn 143, Issue 11, 2013, Pages 1719-1727

  da Silva, Vanessa R ^a,f   Rios Avila, Luisa ^a   Lamers, Yvonne ^a,g   Ralat, Maria A ^a   Midttun, Øivind ^d   Quinlivan, Eoin P ^b   Garrett, Timothy J ^c   Coats, Bonnie ^c   Shankar, Meena N ^b   Percival, Susan S ^a   Chi, Yueh Yun ^b   Muller, Keith E ^b   Ueland, Per Magne ^e   Stacpoole, Peter W ^b,c   Gregory III, Jesse F ^a  

^a UNIVERSITY OF FLORIDA   (United States)

^b UNIVERSITY OF FLORIDA   (United States)

^c UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^d BEVITAL AS   (Norway)

^e UNIVERSITY OF BERGEN   (Norway)

^f UNIVERSITY OF GEORGIA   (United States)

^g UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYKYNURENINE; BIOLOGICAL MARKER; CARBON; CREATINE; CYSTATHIONINE; DIMETHYLGLYCINE; KYNURENIC ACID; PYRIDOXAL 5 PHOSPHATE; PYRIDOXINE; SERINE; TRYPTOPHAN; 3-HYDROXYKYNURENINE; KYNURENINE;

ADULT; ARTICLE; BLOOD LEVEL; CARBON METABOLISM; FEMALE; HUMAN; LIQUID CHROMATOGRAPHY; MALE; METABOLITE; ONE CARBON METABOLISM; PYRIDOXINE DEFICIENCY; TANDEM MASS SPECTROMETRY; TRYPTOPHAN METABOLISM; ANALOGS AND DERIVATIVES; BLOOD; INFLAMMATION; METABOLISM; MULTIVARIATE ANALYSIS; POSTPRANDIAL STATE; YOUNG ADULT;

ADULT; BIOLOGICAL MARKERS; CREATINE; CYSTATHIONINE; FEMALE; HUMANS; INFLAMMATION; KYNURENIC ACID; KYNURENINE; MALE; MULTIVARIATE ANALYSIS; POSTPRANDIAL PERIOD; PYRIDOXAL PHOSPHATE; SERINE; TRYPTOPHAN; VITAMIN B 6; VITAMIN B 6 DEFICIENCY; YOUNG ADULT;

EID: 84886867296     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.3945/jn.113.180588     Document Type: Article

References (80)

1. Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5'-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr. 2008;87:1446-54.
2. CDC. Second National Report on Biochemical Indicators of Diet and Nutrition in the U.S. Population. Atlanta: Department of Health and Human Services; 2012.
3. Cheng CH, Lin PT, Liaw YP, Ho CC, Tsai TP, Chou MC, Huang YC. Plasma pyridoxal 5 '-phosphate and high-sensitivity C-reactive protein are independently associated with an increased risk of coronary artery disease. Nutrition. 2008;24:239-44.
4. Page JH, Ma J, Chiuve SE, Stampfer MJ, Selhub J, Manson JE, Rimm EB. Plasma vitamin B-6 and risk of myocardial infarction in women. Circulation. 2009;120:649-55.
5. Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ. Folate and vitamin B-6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998;279:359-64.
6. Robinson K, Arheart K, Refsum H, Brattstrom L, Boers G, Ueland PM, Rubba P, Palma-Reis R, Meleady R, Daly L, et al. Low circulating folate and vitamin B-6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. Circulation. 1998;97: 437-43.
7. Davis SR, Scheer JB, Quinlivan EP, Coats BS, Stacpoole PW, Gregory JF III. Dietary vitamin B-6 restriction does not alter rates of homocysteine remethylation or synthesis in healthy young women and men. Am J Clin Nutr. 2005;81:648-55.
8. Davis SR, Quinlivan EP, Stacpoole PW, Gregory JF III. Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women. J Nutr. 2006;136:373-8.
9. Lamers Y, Williamson J, Ralat M, Quinlivan EP, Gilbert LR, Keeling C, Stevens RD, Newgard CB, Ueland PM, Meyer K, et al. Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women. J Nutr. 2009;139:452-60.
10. Lamers Y, O'Rourke B, Gilbert LR, Keeling C, Matthews DE, Stacpoole PW, Gregory JF III. Vitamin B-6 restriction tends to reduce the red blood cell glutathione synthesis rate without affecting red blood cell or plasmaglutathione concentrations in healthy men and women. Am J Clin Nutr. 2009;90:336-43.
11. Nijhout HF, Gregory J, Fitzpatrick C, Cho E, Lamers K, Ulrich C, Reed M. A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism. J Nutr. 2009;139: 784-91.
12. Lamers Y, Coats B, Ralat M, Quinlivan EP, Stacpoole PW, Gregory JF III. Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women. J Nutr. 2011;141:835-42.
13. Gregory JF III, Park Y, Lamers Y, Bandyopadhyay N, Chi YY, Lee K, Kim S, da Silva V, Hove N, Ranka S, et al. Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects. PLoS ONE. 2013;8:e63544.
14. Okada M, Suzuki K. Amino acid metabolism in rats fed a high protein diet without pyridoxine. J Nutr. 1974;104:287-93.
15. Park YK, Linkswil H. Effect of vitamin-B6 depletion in adult man on plasma concentration and urinary excretion of free amino acids. J Nutr. 1971;101:185-91.
16. Swendseid ME, Villalobos J, Friedrich B. Free amino acids in plasma and tissues of rats fed a vitamin B6-deficient diet. J Nutr. 1964;82:206-8.
17. Scheer JB, Mackey AD, Gregory JF. Activities of hepatic cytosolic and mitochondrial forms of serine hydroxymethyltransferase and hepatic glycine concentration are affected by vitamin B-6 intake in rats. J Nutr. 2005;135:233-8.
18. Runyan TJ, Gershoff SN. Glycine metabolism in vitamin B6-deficient and deoxypyridoxine-treated rats. J Nutr. 1969;98:113-8.
19. Leklem JE. Vitamin B-6: a status report. J Nutr. 1990;120 Suppl 11: 1503-7.
20. Gregory J. Vitamin B6 deficiency. In: Carmel R, Jacobsen D, editors. Homocysteine in health and disease. Cambridge (UK): Cambridge University Press; 2001. p. 307-20.
21. Midttun Ø, Hustad S, Schneede J, Vollset SE, Ueland PM. Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study. Am J Clin Nutr. 2007;86:131-8.
22. Wolf H. Studies on tryptophan metabolism in man: the effects of hormones and vitamin B6 on urinary excretion of metabolites of the kynurenine pathway. Scand J Clin Lab Invest Suppl. 1974;33:11-87.
23. Paul L, Ueland PM, Selhub J. Mechanistic perspective on the relationship between pyridoxal 5#-phosphate and inflammation. Nutr Rev. 2013;71:239-44.
24. Oxenkrug GF. Interferon-gamma-inducible kynurenines/pteridines inflammation cascade: implications for aging and aging-associated psychiatric and medical disorders. J Neural Transm. 2011;118:75-85.
25. Sakakeeny L, Roubenoff R, Obin M, Fontes JD, Benjamin EJ, Bujanover Y, Jacques PF, Selhub J. Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of inflammation in a population of U.S. adults. J Nutr. 2012;142:1280-5.
26. Suzuki Y, Suda T, Furuhashi K, Suzuki M, Fujie M, Hahimoto D, Nakamura Y, Inui N, Nakamura H, Chida K. Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer. Lung Cancer. 2010;67:361-5.
27. Sprince H, Lowy RS, Folsome CE, Behrman JS. Studies on the urinary excretion of "xanthurenic acid" during normal and abnormal pregnancy: a survey of the excretion of "xanthurenic acid" in normal nonpregnant, normal pregnant, pre-eclamptic, and eclamptic women. Am J Obstet Gynecol. 1951;62:84-92.
28. Rose DP, Braidman IP. Excretion of tryptophan metabolites as affected by pregnancy, contraceptive steroids, and steroid hormones. Am J Clin Nutr. 1971;24:673-83.
29. Rose DP. Excretion of xanthurenic acid in the urine of women taking progestogen-oestrogen preparations. Nature. 1966;210:196-7.
30. Rose DP, Adams PW. Oral contraceptives and tryptophan metabolism: effects of oestrogen in low dose combined with a progestagen and of a low-dose progestagen (megestrol acetate) given alone. J Clin Pathol. 1972;25:252-8.
31. Bender DA, Tagoe CE, Vale JA. Effects of oestrogen administration on vitamin B6 and tryptophan metabolism in the rat. Br J Nutr. 1982;47: 609-14.
32. Price SA, Rose DP, Toseland PA. Effects of dietary vitamin B 6 deficiency and oral contraceptives on the spontaneous urinary excretion of 3-hydroxyanthranilic acid. Am J Clin Nutr. 1972;25:494-8.
33. Yess N, Price JM, Brown RR, Swan PB, Linkswiler H. Vitamin B6 depletion in man: urinary excretion of tryptophan metabolites. J Nutr. 1964;84:229-36.
34. Brown RR, Yess N, Price JM, Linkswiler H, Swan P, Hankes LV. Vitamin B6 depletion in man: urinary excretion of quinolinic acid and niacin metabolites. J Nutr. 1965;87:419-23.
35. Yeh JK, Brown RR. Effects of vitamin B-6 deficiency and tryptophan loading on urinary excretion of tryptophan metabolites in mammals. J Nutr. 1977;107:261-71.
36. Tanaka T, Knox WE. The nature and mechanism of the tryptophan pyrrolase (peroxidase-oxidase) reaction of pseudomonas and of rat liver. J Biol Chem. 1959;234:1162-70.
37. Knox WE, Mehler AH. The adaptive increase of the tryptophan peroxidase-oxidase system of liver. Science. 1951;113:237-8.
38. Schutz G, Killewich L, Chen G, Feigelson P. Control of the mRNA for hepatic tryptophan oxygenase during hormonal and substrate induction. Proc Natl Acad Sci USA. 1975;72:1017-20.
39. Altman K, Greengard O. Correlation of kynurenine excretion with liver tryptophan pyrrolase levels in disease and after hydrocortisone induction. J Clin Invest. 1966;45:1527-34.
40. Knox WE, Auerbach VH. The hormonal control of tryptophan peroxidase in the rat. J Biol Chem. 1955;214:307-13.
41. Wolf H, Brown RR. Studies on tryptophan metabolism in male subjects treated with hydrocortisone. J Clin Endocrinol Metab. 1971;33:838-43.
42. Nakamura T, Shinno H, Ichihara A. Insulin and glucagon as a new regulator system for tryptophan oxygenase activity demonstrated in primary cultured rat hepatocytes. J Biol Chem. 1980;255:7533-5.
43. Braidman IP, Rose DP. Effects of sex hormones on three glucocorticoidinducible enzymes concerned with amino acid metabolism in rat liver. Endocrinology. 1971;89:1250-5.
44. Taylor MW, Feng GS. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 1991;5: 2516-22.
45. Shimizu T, Nomiyama S, Hirata F, Hayaishi O. Indoleamine 2,3-dioxygenase. Purification and some properties. J Biol Chem. 1978;253: 4700-6.
46. Dalgliesh CE, Knox WE, Neuberger A. Intermediary metabolism of tryptophan. Nature. 1951;168:20-2.
47. Ogasawara N, Hagino Y, Kotake Y. Kynurenine-transaminase, kynureninase and the increase of xanthurenic acid excretion. J Biochem. 1962;52:162-6.
48. Takeuchi F, Shibata Y. Kynurenine metabolism in vitamin-B-6-deficient rat liver after tryptophan injection. Biochem J. 1984;220:693-9.
49. Wiss O, Fuchs H. [Splitting of kynurenine, oxykynurenine an related substances by the rat liver enzyme]. Experientia. 1950;6:472-3.
50. NakataniM, MorimotoM, Noguchi T, Kido R. Subcellular distribution and properties of kynurenine transaminase in rat liver. Biochem J. 1974; 143:303-10.
51. Rios-Avila L, Nijhout HF, Reed MC, Sitren HS, Gregory JF. A mathematical model of tryptophan metabolism via the kynurenine pathway provides insights into the effects of vitamin B6 deficiency, tryptophan loading and induction of tryptophan 2,3-dioxygenase on tryptophan metabolites. J Nutr. 2013:Jul 31 (Epub ahead of print; DOI:10.3945/jn.113.174599).
52. Midttun O, Ulvik A, Ringdal Pedersen E, Ebbing M, Bleie O, Schartum-Hansen H, Nilsen RM, Nygard O, Ueland PM. Low plasma vitamin B-6 status affects metabolism through the kynurenine pathway in cardiovascular patients with systemic inflammation. J Nutr. 2011;141:611-7.
53. Theofylaktopoulou D,Midttun O, Ulvik A, Ueland PM, Tell GS, Vollset SE, Nygard O, Eussen SJ. A community based study on determinants of circulating markers of cellular immune activation and kynurenines: the Hordaland Health Study. Clin Exp Immunol. 2013;173:121-30.
54. Gregory JF III, Park Y, Lamers Y, Bandyopadhyay N, Chi Y-Y, Lee K, Kim S, da Silva V, Hove N, et al. Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects. PLoS ONE. 2013;8:e63544.
55. Ubbink JB, Serfontein WJ, Devilliers LS. Stability of pyridoxal-5-phosphate semicarbazone: applications in plasma vitamin-B6 analysis and population surveys of vitamin-B6 nutritional-status. J Chromatogr. 1985;342:277-84.
56. Pfeiffer CM, Huff DL, Gunter EW. Rapid and accurate HPLC assay for plasma total homocysteine and cysteine in a clinical laboratory setting. Clin Chem. 1999;45:290-2.
57. Ueland PM, Midttun O, Windelberg A, Svardal A, Skalevik R, Hustad S. Quantitative profiling of folate and one-carbon metabolism in largescale epidemiological studies by mass spectrometry. Clin Chem Lab Med. 2007;45:1737-45.
58. Midttun Ø, Hustad S, Ueland PM. Quantitative profiling of biomarkers related to B-vitamin status, tryptophan metabolism and inflammation in human plasma by liquid chromatography/tandem mass spectrometry. Rapid communications in mass spectrometry. Rapid Commun Mass Spectrom. 2009;23:1371-9.
59. Chi YY, Gribbin M, Lamers Y, Gregory JF, Muller KE. Global hypothesis testing for high-dimensional repeated measures outcomes. Stat Med. 2012;31:724-42.
60. Storey JD. A direct approach to false discovery rates. J R Stat Soc: Series B Stat Methodol. 2012;64:479-98.
61. Arani RB, Chen JJ. A power study of a sequential method of P-value adjustment for correlated continuous endpoints. J Biopharm Stat. 1998;8:585-98.
62. Westerhuis JA, van Velzen EJ, Hoefsloot HC, Smilde AK. Multivariate paired data analysis: multilevel PLSDA versus OPLSDA. Metabolomics. 2010;6:119-28.
63. Wold S, Sjostrom M, Eriksson L. PLS-regression: a basic tool of chemometrics. Chemometr Intell Lab. 2001;58:109-30.
64. Umetrics M. User guide to SIMCA. Malmö (Sweden): MKS Umetrics AB; 2013.
65. Efron B, Gong G. A leisurely look at the bootstrap, the jackknife, and cross-validation. Am Stat. 1983;37:36-48.
66. Wiklund S, Johansson E, Sjostrom L, Mellerowicz EJ, Edlund U, Shockcor JP, Gottfries J, Moritz T, Trygg J. Visualization of GC/TOFMS-based metabolomics data for identification of. Anal Chem. 2008;80:115-22.
67. Larsson SC, Orsini N,Wolk A. Vitamin B-6 and risk of colorectal cancer a meta-analysis of prospective studies. JAMA. 2010;303:1077-83.
68. Lotto V, Choi SW, Friso S. Vitamin B6: a challenging link between nutrition and inflammation in CVD. Br J Nutr. 2011;106:183-95.
69. Eussen SJ, Vollset SE, Hustad S, Midttun O, Meyer K, Fredriksen A, Ueland PM, Jenab M, Slimani N, Boffetta P, et al. Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2010;19:2549-61.
70. Cuskelly GJ, Stacpoole PW, Williamson J, Baumgartner TG, Gregory JF III. Deficiencies of folate and vitamin B(6) exert distinct effects on homocysteine, serine, and methionine kinetics. Am J Physiol Endocrinol Metab. 2001;281:E1182-90.
71. Morris MS, Sakakeeny L, Jacques PF, Picciano MF, Selhub J. Vitamin B-6 intake is inversely related to, and the requirement is affected by, inflammation status. J Nutr. 2010;140:103-10.
72. Ulvik A, Midttun O, Pedersen ER, Nygard O, Ueland PM. Association of plasma B-6 vitamers with systemic markers of inflammation before and after pyridoxine treatment in patients with stable angina pectoris. Am J Clin Nutr. 2012;95:1072-8.
73. Lima CP, Davis SR, Mackey AD, Scheer JB, Williamson J, Gregory JF III. Vitamin B-6 deficiency suppresses the hepatic transsulfuration pathway but increases glutathione concentration in rats fed AIN-76A or AIN-93G diets. J Nutr. 2006;136:2141-7.
74. Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ. The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest. 1996;98:177-84.
75. Moskovitz J, Berlett BS, Poston JM, Stadtman ER. Methionine sulfoxide reductase in antioxidant defense.Methods Enzymol. 1999;300: 239-44.
76. Bö ger RH, Bode-Böger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, Blaschke TF, Cooke JP. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction. Circulation. 1998;98:1842-7.
77. Brosnan JT, da Silva RP, Brosnan ME. The metabolic burden of creatine synthesis. Amino Acids. 2011;40:1325-31.
78. Martinez M, Cuskelly GJ, Williamson J, Toth JP, Gregory JF. Vitamin B-6 deficiency in rats reduces hepatic serine hydroxymethyltransferase and cystathionine beta-synthase activities and rates of in vivo protein turnover, homocysteine remethylation and transsulfuration. J Nutr. 2000;130:1115-23.
79. van de Kamp JL, Smolen A. Response of kynurenine pathway enzymes to pregnancy and dietary level of vitamin B-6. Pharmacol Biochem Behav. 1995;51:753-8.
80. Zhao M, Lamers Y, Ralat MA, Coats BS, Chi YY, Muller KE, Bain JR, Shankar MN, Newgard CB, Stacpoole P, et al. Marginal vitamin B-6 deficiency decreases plasma (n-3) and (n-6) PUFA concentrations in healthy men and women. J Nutr. 2012;142:1791-7.