Two pathways for methionine degradation exist. A knowledge of the relative importance of these two pathways transaminative vs transsulfuration) in the degradation of methionine is important because it provides vital information for treatment of individuals with inherited disorders of sulfur amino acid metabolism. We propose to utilize the continuous infusion isotope dilution technique to develop a model of methionine metabolism in the pig. The model, as currently envisioned, requires two separate infusions involving a combination of five separate, specifically labeled metabolites. The pig was selected as the experimental animal because it seems to be an appropriate model for methionine metabolism in man because the metabolism of methionine by liver homogenates is similar in pigs and monkeys. The model will be used to determine the effect of age, young (10 kg) vs old (100 kg) pigs and level of methionine 75, 100 or 150% of the requirement on the importance of these two pathways of methionine catabolism. The studies in relation to methionine level are critical because the importance of the pathways of methionine metabolism are not known in relation to methionine level and the toxicity of methionine is thought to be related to the metabolism of methionine via the transaminative pathways. These studies may help explain why young are more susceptible to methionine toxicity than older animals if the results obtained show markedly different activities of methionine metabolism in the 10 and 100 kg animals. Other studies utilize the model of methionine metabolism in vitamin B-6 deficient pigs because this deficiency is thought to be a reasonable model for homocystinuria. Our suggestion that the beneficial effect of betaine supplementation to cystathionine synthase deficient homocystinuric patients is because methione is metabolized by the transaminative pathways make these studies important.
|Benevenga, N J; Odle, J; Asche, G L (1992) Comparison of measured carbon dioxide production with that obtained by the isotope dilution technique in neonatal pigs: observations on site of infusion. J Nutr 122:2174-82|