Waste Products of Nitrogen Metabolism
	Proteins and nucleic acids are the two main sources of nitrogenous wastes. Proteins are the source of over 95% of the total amount of excreted nitrogen; nucleic acids make up the remaining 5%. The major problem is to get rid of the ammonia (NH3) that forms when amino groups (–NH2) are removed from amino acids during protein catabolism. Because ammonia is a very toxic molecule, it is kept in low concentrations. In the blood of vertebrates the range is 0.0001 to 0.003 mg/100 ml. Higher concentrations can be lethal; for example, a mouse will die if the ammonia concentration in its blood reaches 5 mg/100 ml. Some animals excrete nitrogenous wastes directly as ammonia, but many species convert it to urea or uric acid immediately after it forms. These compounds are much less toxic which permits them to be transported and stored until they can be excreted. The animals that excrete nitrogenous wastes as ammonia need access to lots of water; therefore, ammonia excretion is most common in aquatic species. Because ammonia molecules are small, they easily pass through membranes and are lost by diffusion to the surrounding water. In many invertebrates, ammonia release occurs across the whole body surface. Teleost (bony) fishes excrete almost all of their nitrogen as ammonia through the gills and in the urine. Excretion of most of the nitrogen as ammonia is called ammonotelic excretion.
Although it works well in many aquatic species, ammonia excretion is much less suitable for land animals. Because it is so toxic, ammonia can only be transported and excreted in large volumes of very dilute solutions, and most terrestrial animals and many marine species (which tend to lose water to their environment by osmosis) simply do not have access to sufficient water. Instead, mammals, most adult amphibians, and many marine fishes and turtles excrete mainly urea. Excretion of urea as the primary nitrogenous waste is called ureotelic excretion. In a third category are animals that, because of their dry habitats (or some other reason requiring water conservation), excrete a minimal amount of urine that contains little or no water. These animals (e.g., land snails, insects, birds, some frogs and many reptiles) convert ammonia to uric acid. Unlike ammonia or urea, uric acid is insoluble in water, so only small amounts are retained in solution–greatly limiting their toxicity. (For any substance to be toxic and achieve a biological effect, it must be in solution.) Excretion of nitrogen in the form of uric acid is called uricotelic excretion. Most uricotelic animals excrete their nitrogenous waste as solid or semi-solid urine, or as uric acid crystals. Ammonia, urea and uric acid are the most common nitrogenous waste products, but not the only ones. Some sharks secrete trimethylamine oxide (TMO). A variety of animals also excrete small quantities of creatine and creatinine. Some animals even wastefully excrete some of their excess amino acids. Because urea, uric acid and TMO are less toxic than ammonia, why don’t more animals excrete most of their nitrogen in these forms? The answer can be explained as “biological economics”. The synthesis of these compounds is energetically costly. Nearly half of the food energy a terrestrial insect consumes may be used to process metabolic wastes! In aquatic insects, ammonia simply diffuses out of the body into the surrounding water. In general, an animal excretes its nitrogen in a form requiring the least expenditure of energy, given the environment in which it lives. A few animals excrete nitrogen that comes from the metabolism of purines (e.g., adenine and guanine). Purines can be broken down to ammonia only if the animal has the specific enzymes. Most animals excrete purine nitrogen as uric acid or as one or more intermediate products.