Experimental alteration of tryptophan metabolism by methionine: Neuropharmacologic implications

The amino acids tryptophan and methionine are known to be involved in behavioral alterations and their metabolites have been implicated in mental illness. To learn more about the metabolic interrelationships of these two amino acids, rats were placed on amino acid diets deficient in nicotinic acid and nicotinamide and pair-fed with and without intestinal-antibiotics. Excess methionine (4%) added to such diets resulted in rats showing a decrease in body weight and urinary N¹-methylnicotinamide (MNA) and an increase in urinary xanthurenic acid (XA) and total indoleacetic acid (TIAA) in comparison with controls. Urinary creatinine (CR) was relatively unchanged. Intestinal-antibiotics did not affect the overall methionine effect. The overall results demonstrate that excess-dietary methionine alters the tissue metabolism of tryptophan, and gives rise to urinary excretion patterns of tryptophan metabolites claimed to occur in mental illness. The observed data point to a metabolic alteration involving vitamin B₆. A natural competition may exist between methionine and tryptophan for vitamin B₆ which is utilized in the metabolic pathways of both amino acids. Our work suggests that tolerance load tests of methionine and tryptophan in behavioral alteration studies must take into account the metabolic competition between these two amino acids for vitamin B₆, as well as the formation of psychotogenic metabolites by N-methylation and O-methylation reactions.