Mechanisms and kinetics of heme iron nitrosylation in an in vitro gastro-intestinal model

- Nitrosyl heme is formed in gastro-intestinal conditions.
- Nitrosylation is optimal in mildly acidic conditions.
- Antioxidants decrease nitrosylation.

Fresh red meat and cured meat consumption increases the risk of gastro-intestinal cancers and it is strongly suspected that nitrosylheme is implicated by stimulating the endogenous production of mutagenic aldehydes and N-nitroso compounds. To investigate the extent of endogenous heme iron nitrosylation an experimental in vitro model that mimics the physicochemical conditions of the gastro-intestinal tract was used in association with a mathematical model of chemical reaction kinetics. The combined effect of pH (from 7.2 to 3.2) and myoglobin oxidation state was evaluated in the reaction of nitrite with heme iron, and the observed rate constants of the reactions were determined. Nitrosylation was optimal under mildly acidic conditions (pH 6.5-4.7). Up to 20% of myoglobin can be nitrosylated under gastro-intestinal conditions in this pH range. The effect of various antioxidants (from meat or vegetables) on the endogenous nitrosylation process was also tested.