Homocysteine (Hcy) is a sulphur containing amino acid, derived from the metabolism of methionine. Elevated Hcy plasma concentrations result in hyperhomocysteinemia, a risk factor for cardiovascular disease. The causes are genetic defects of the key enzymes, acquired conditions, or a combination of both. In this study we assessed the effects of nitric oxide on Hcy, cysteine (Cys) and cysteinal-glycine (Cys-Gly) production by the rat hepatoma HTC cells, using the NO-donor, diethylamine NO-NOate (DEA-NO). D E A -N O caused a dose and time-dependent increase in the production of Hcy: at 500pM it caused a 3-fold increase in the levels of Hcy, Cys and Cys-Gly, whilst at 50pM increased Hcy and Cys-Gly 2.5-fold, but had no effect on Cys levels. In all experiments the NO-donor effect was apparent within 4h and maintained for 24h. Using DEA-NO, 5pM, increased production of Hcy and Cys-Gly was only observed at 4h and was indistinguishable from control levels at 24h. Experiments performed with exhausted NO-donor showed that N O -N O a t e had no effect on Hcy production indicating that the effects were due to NO alone. These results demonstrate that NO, at physiologically relevant concentrations, increase cellular Hcy production and may contribute to hyperhomocysteinemia.
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