title: Vitamin B-6 deficiency suppresses the hepatic transsulfuration pathway but increases glutathione concentration in rats fed AIN-76A or AIN-93G diets.
abstract: The transsulfuration pathway, which aids in regulating homocysteine concentration and mediates cysteine synthesis, may be sensitive to vitamin B-6 status because cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CGL) require pyridoxal 5'-phosphate (PLP). To assess relations between vitamin B-6 and transsulfuration, we evaluated the effects of dietary pyridoxine (PN) on the hepatic concentration of relevant metabolites and in vitro activity of CBS and CGL. Growing rats were fed AIN-93G- or AIN-76A-based diets that ranged from adequate to deficient in vitamin B-6 (2, 1, 0.5, 0.1, or 0 mg of PN/kg diet, n = 5). This design allowed assessment of the effects of supplemental methionine (AIN-76A) vs. cysteine (AIN-93G) in common research diets over a range of vitamin B-6 levels. CBS activity, assayed in the presence or absence of added S-adenosylmethionine, was independent of diet type and PN level. CGL activity was independent of diet type but proportional to dietary PN. Rats fed deficient (0 and 0.1 mg PN/kg) diets exhibited only approximately 30% of the CGL activity of those fed the 2 mg PN/kg diets. Hepatic cystathionine increased from 20 to 30 nmol/g for the 1-2 mg PN/kg diets to approximately 85 nmol/g for the 0 mg PN/kg diet; however, cysteine was reduced only in B-6-deficient rats consuming the AIN-93G diet (means of 30-40 nmol/g for adequate to 11.6 nmol/g for 0 mg PN/kg AIN-76A diet). In spite of these effects, hepatic glutathione concentration increased in vitamin B-6 deficiency. These results suggest that vitamin B-6-dependent changes in transsulfuration do not limit hepatic glutathione production.
authors.affiliation: Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA.
authors.forename: Carolina P
authors.initials: CP
authors.lastname: Lima
authors.forename: Steven R
authors.initials: SR
authors.lastname: Davis
authors.forename: Amy D
authors.initials: AD
authors.lastname: Mackey
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Scheer
authors.forename: Jerry
authors.initials: J
authors.lastname: Williamson
authors.forename: Jesse F
authors.initials: JF
authors.lastname: Gregory
mesh_terms: D000818:Animals; D003541:Cystathionine beta-Synthase / Q000378:metabolism*; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D003545:Cysteine / Q000008:administration & dosage* / Q000494:pharmacology; D004032:Diet; D005978:Glutathione / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000494:pharmacology; D009751:Nutritional Requirements; D011736:Pyridoxine / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D026681:Vitamin B 6 Deficiency / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D008715:Methionine; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D005978:Glutathione; D003545:Cysteine; D011736:Pyridoxine