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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Plasma Glutathione and Cystathionine Concentrations Are Elevated but Cysteine Flux Is Unchanged by Dietary Vitamin B-6 Restriction in Young Men and Women^1,2

Steven R. Davis^*, Eoin P. Quinlivan^*, Peter W. Stacpoole^,** and Jesse F. Gregory, III^*,3

^* Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, Division of Endocrinology and Metabolism, Department of Medicine, and ^** Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611-0370

³ To whom correspondence and reprint requests should be addressed: E-mail: jfgy{at}ufl.edu.

Cysteine synthesis from homocysteine is catalyzed by two pyridoxal 5'-phosphate (PLP)-dependent enzymes. This suggests that vitamin B-6 status might affect cysteine and glutathione homeostasis, but it is unclear whether this occurs in humans. We assessed the effects of vitamin B-6 status on static and kinetic parameters of cysteine and glutathione metabolism in healthy female (n = 5) and male (n = 4) volunteers (20–30 y) before and after 4 wk of dietary vitamin B-6 restriction (<0.5 mg vitamin B-6/d). Rates of reactions related to cysteine metabolism were measured from blood sampled during primed, constant infusions of [¹³C₅]methionine, [3-¹³C]serine, and [²H₂]cysteine that were conducted after an overnight fast at baseline and after the dietary protocol. Vitamin B-6 restriction reduced the concentration of PLP (55.1 ± 8.3 vs. 22.6 ± 1.3 nmol/L; P = 0.004) and increased concentrations of cystathionine (124%; P < 0.001) and total glutathione (38%; P < 0.008) in plasma. Concentrations of plasma homocysteine, cysteine, cysteinylglycine, and C-reactive protein (an indicator of systemic inflammation) were not affected by dietary vitamin B-6 restriction. The rate of cysteine synthesis via transsulfuration was below detection limits in this protocol. Neither the fractional synthesis rate of cystathionine nor whole-body cysteine flux was affected by vitamin B-6 restriction. These data indicate that glutathione homeostasis is altered by dietary vitamin B-6 deficiency and appears to be unrelated to cysteine flux under conditions of minimal amino acid intake as evaluated in this study.

KEY WORDS: • cysteine • glutathione • human • transsulfuration • vitamin B-6

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