Nitrogen Metabolism

Nitrogen enters the body in a variety of compounds present in food, the most important being amino acids contained in dietary protein. Nitrogen leaves the body as urea, ammonia, and other products derived from amino acid metabolism (Fig. 1). Free amino acids in the body are produced by hydrolysis of dietary protein by proteases activated from their zymogen form in the stomach and intestine, degradation of tissue proteins, and de novo synthesis. This amino acid pool is consumed in the synthesis of body protein, metabolized for energy, or its members used as precursors for other nitrogen-containing compounds. Free amino acids from digestion are taken up by intestinal enterocytes via sodium-dependent secondary active transport. Small peptides are taken up via proton-linked transport. Note that body protein is simultaneously degraded and resynthesized, a process known as protein turnover. The concentration of a cellular protein may be determined by regulation of its synthesis or degradation. The ATP dependent,  cytosolic, selective ubiquitin–proteasome and ATP independent,  relatively nonselective lysosomal acid hydrolases are the two major enzyme systems that are responsible for degrading proteins. Nitrogen cannot be stored, and amino acids in excess of the biosynthetic needs of the cell are quickly degraded. The first phase of catabolism involves the transfer of the α-amino groups through transamination by pyridoxal phosphate–dependent aminotransferases (transaminases), followed by oxidative deamination of glutamate by glutamate dehydrogenase, forming ammonia and the corresponding α-keto acids. A portion of the free ammonia is excreted in the urine. Some ammonia is used in converting glutamate to glutamine for safe transport, but most is used in the hepatic synthesis of urea, which is quantitatively the most important route for disposing of nitrogen from the body. Alanine also carries nitrogen to the liver for disposal as urea. The two major causes of hyperammonemia (with its neurologic effects) are acquired liver disease and congenital deficiencies of urea cycle enzymes such as X-linked ornithine transcarbamylase.

Figure 1: Key concept map for nitrogen metabolism. GI = gastrointestinal;  PEST = proline, glutamate, serine, threonine; NH3 = ammonia; CO2 = carbon dioxide.