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.

Impairments in pyridoxine-dependent sulphur amino acid metabolism are highly sensitive to the degree of vitamin B6 deficiency and repletion in the pig

“…In the current study, decreases in both the apo-and total activities of hepatic CBS, CGL and SHMT were observed after 6 weeks of vitamin B 6 depletion, consistent with observations from rat studies (Smolin and Benevenga, 1984;Lima et al, 2006), although the magnitude of changes differed from published reports. In particular, the activities of hepatic apo-CBS and CGL were 9% and 45% of control animals, respectively, in the current trial.…”

“…In particular, the activities of hepatic apo-CBS and CGL were 9% and 45% of control animals, respectively, in the current trial. Earlier authors have reported reductions of apo-CGL activities in rats receiving semi-purified diet without addition of pyridoxine to 30% of control animal values, where rats were receiving 2 mg/kg pyridoxine, with no change in apo-CBS activities (Lima et al, 2006). However, the current data support the position that, in the young pig, both CBS and CGL are sensitive to a 6-week vitamin B 6 -depletion period.…”

“…Pyridoxal-5 0 -phosphate (PLP), a major biological form of vitamin B 6 in animal tissues, is a well established co-factor for the three enzymes directly involved in homocysteine disposition: cystathionine-bsynthase (CBS) and cystathionine-g-lyase (CGL) are key PLP-dependent enzymes in the transsulphuration pathway, and serine hydroxymethyltransferase (SHMT) is a PLPdependent enzyme important for the folate cycle and one carbon metabolism (House et al, 1999). Vitamin B 6 status and, therefore, nutritional supply are thus implicated in the regulation of homocysteine flux and overall sulphur amino acid metabolism (Smolin and Benevenga, 1982;Davis et al, 2005;Lima et al, 2006).…”

Methionine + cystine levels and vitamin B6 supplementation on performance and enzyme expression of methionine metabolism of gilts from 75 to 100 kg

“…However, when the methionine concentration is low, S-adenosylmethionine concentrations decrease and cystathionine β-synthase activity is restored to normal levels, conserving homocysteine for remethylation (Prudova et al, 2006;Nijhout et al, 2006). The deficiency of some vitamins (B 6 , B 12 , and folate) that act as enzymatic cofactors may also change the activity of the enzymes involved in methionine metabolism, impairing the control of homocysteine concentrations (Lima et al, 2006;Zhang et al, 2009).…”

Vitamin B6 Deficiency, Genome Instability and Cancer

“…In mammals and birds δ-aminolevulinic acid is synthesized by the action of δ-aminolevulinic acid synthase and in plants and algae by the action of glutamate-1-semialdehyde 2, 1-aminomutase (Raschle et al, 2008). Additionally, in plants the biosynthesis of the phytohormone ethylene is controlled by the synthesis of the precursor 1-aminocyclopropane-1-carboxylic acid from S-adenosylmethionine by PLP dependent 1-aminocyclopropane-1-carboxylate synthases (Lima et al, 2006;Kappes et al, 2011). This underlines the wide variety of chemical reactions that PLP-dependent enzymes promote in the organisms and shows again the importance of vitamin B6.…”