Ammonia: its effects on biological systems, metabolic hormones, and reproduction

The physical, chemical properties of ammonia, its sources and detoxification, its effects in biological systems, its influence upon insulin action and glucose metabolism, and its possible effects on reproduction are discussed. Present chemical methods do not distinguish nonionic from ionic forms. At physiological pH, nonionic ammonia concentrations remain low but are primarily responsible for toxic effects. Thus, biologically significant changes of ammonia concentrations may not be revealed by determinations of ammonia in blood plasma. For these and other reasons the subacute toxicity of ammonia often is unrecognized, and its effects on intermediary metabolism and the hormonal milieu in normal and disease states remain poorly understood. Effects of ammonia may be stimulatory at low concentrations and inhibitory as concentrations rise or exposure is extended. Extensive experiments in eight ureotelic species, including man, show that urinary excretion of orotic acid becomes significantly elevated when the quantity of ammonia presented to the liver exceeds the capacity for normal detoxification. Present evidence with arginine and other intermediates of the urea cycle suggest that these substances influence glucose metabolism and insulin action. Recent studies of dairy cattle provide speculative evidence that high protein feeding or forms of protein that lead to elevated ammonia concentrations in tissue decrease conception rates and increase the calving to conception interval of dairy cows. Limited data concerning luteinizing hormone concentrations and steroid hormone metabolism are insufficient to establish whether differences in reproductive performance are due to changes of hormonal physiology, intrauterine environment, or metabolism.