Vitamin B-6 restriction reduces the production of hydrogen sulfide and its biomarkers by the transsulfuration pathway in cultured human hepatoma cells.
J Nutr
; 144(10): 1501-8, 2014 Oct.
Article
en En
| MEDLINE
| ID: mdl-25165392
ABSTRACT
BACKGROUND:
Pyridoxal 5'-phosphate (PLP) functions as a coenzyme in many cellular processes including one-carbon metabolism and the interconversion and catabolism of amino acids. PLP-dependent enzymes, cystathionine ß-synthase and cystathionine γ-lyase, function in transsulfuration but also have been implicated in the production of the endogenous gaseous signaling molecule hydrogen sulfide (H2S) concurrent with the formation of the biomarkers lanthionine and homolanthionine.OBJECTIVE:
Our objective was to determine if H2S production and concurrent biomarker production is affected by vitamin B-6 restriction in a cell culture model.METHODS:
We used cultured human hepatoma cells and evaluated static intracellular profiles of amino acids and in vivo kinetics of H2S biomarker formation. Cells were cultured for 6 wk in media containing concentrations of pyridoxal that represented severe vitamin B-6 deficiency (15 nmol/L pyridoxal), marginal deficiency (56 nmol/L pyridoxal), adequacy (210 nmol/L pyridoxal), and standard medium formulation providing a supraphysiologic pyridoxal concentration (1800 nmol/L pyridoxal).RESULTS:
Intracellular concentrations of lanthionine and homolanthionine in cells cultured at 15 nmol/L pyridoxal were 50% lower (P < 0.002) and 47% lower (P < 0.0255), respectively, than observed in cells cultured at 1800 nmol/L pyridoxal. Extracellular homocysteine and cysteine were 58% and 46% higher, respectively, in severely deficient cells than in adequate cells (P < 0.002). Fractional synthesis rates of lanthionine (P < 0.01) and homolanthionine (P < 0.006) were lower at 15 and 56 nmol/L pyridoxal than at both higher pyridoxal concentrations. The rate of homocysteine remethylation and the fractional rate of homocysteine production from methionine were not affected by vitamin B-6 restriction. In vitro studies of cell lysates using direct measurement of H2S also had a reduced extent of H2S production in the 2 lower vitamin B-6 conditions.CONCLUSION:
In view of the physiologic roles of H2S, these results suggest a mechanism that may be involved in the association between human vitamin B-6 inadequacy and its effects on human health.
Texto completo:
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Deficiencia de Vitamina B 6
/
Biomarcadores
/
Vitamina B 6
/
Sulfuro de Hidrógeno
Límite:
Humans
Idioma:
En
Revista:
J Nutr
Año:
2014
Tipo del documento:
Article