AHS17

Protein is essential to life and health, but its metabolic byproduct, ammonia, is toxic. Humans dispose of excess nitrogen largely as urea, a nontoxic metabolite of ammonia that can be safely excreted in the urine. Rare genetic defects interfere directly with the production of urea. Other genetic defects that interfere with the use of certain fuels, especially branched-chain amino acids, can indirectly impair the synthesis of urea during metabolic crisis. Impairments of urea synthesis lead to the accumulation of ammonia, with devastating neurological consequences. Null genes manifest in infancy and are best studied. Partial genetic deficiencies are often asymptomatic through adulthood until dietary changes (protein supplementation, carbohydrate restriction, fasting) or metabolic demands (intense exercise, illness) force a greater rate of protein catabolism. Whether more common polymorphisms in these pathways lead to variations in the tolerance to protein or the conditions that require its catabolism remains largely unexplored, but critically important.