Amino acid nitrogen metabolism

Marchesini G, Fabbri A, Bianchi G, et al. Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology 1996 23 1084-1092. 

Transamination channels a-amino acid nitrogen into glutamate. L-Glutamate dehydrogenase (GDH) occupies a central position in nitrogen metabolism. 

Dehydrogenase Deficiency, Biotinidase Deficiency, and Adrenoleukodystrophy. Catabolism of essential amino acid skeletons is discussed in the chapters Phenylketonuria and HMG-CoA Lyase Deficiency. The chapters Inborn Errors of Urea Synthesis and Neonatal Hyperbilirubinemia discuss the detoxification and excretion of amino acid nitrogen and of heme. The chapter Gaucher Disease provides an illustration of the range of catabolic problems that result in lysosomal storage diseases. Several additional chapters deal with key aspects of intracellular transport of enzymes and metabolic intermediates the targeting of enzymes to lysosomes (I-Cell Disease), receptor-mediated endocytosis (Low-Density Lipoprotein Receptors and Familial Hypercholesterolemia) and the role of ABC transporters in export of cholesterol from the cell (Tangier disease). 

Amino acids differ from carbohydrates and fats in that they contain nitrogen as part of their molecular structure. For the carbons in amino acids to enter into the energy generating metabolic pathways, the amino groups must first be removed so that they can be detoxified and excreted. The amino acid nitrogen is excreted predominantly as urea, but some is also excreted as free ammonia in order to buffer the urine. 

Coomes MW. Amino acid metabolism. In Devlin TM, ed. Textbook of Biochemistry with Clinical Correlations, 5th ed. New York Wiley-Liss, 2002. Rodwell VW. Catabohsm of proteins of amino acid nitrogen. In Murray RK, Granner DK, Mayes PA, et al. Harper s Illustrated Biochemistry, 26th ed. New York Lange Medical Books/McGraw-Hill, 2003. 

Willcock, E. G. and Hopkins, F. G., The importance of individual amino acids in metabolism. Observations on the effect of adding tryptophane to a diet in which zein is the sole nitrogenous constituent, /. Physiol., 35, 88, 1906. 

Organisms other than plants vary widely in their capacity to synthesize amino acids from metabolic intermediates and fixed nitrogen. For example, many microorganisms can produce all the amino acids they need. In contrast, animals can synthesize only about half the amino acids they require. The nonessential amino acids (NAA) are synthesized from readily available metabolites. The amino acids that must be provided in the diet to ensure proper nitrogen balance and adequate growth are referred to as essential amino adds (EAA). 

When amino acids are metabolized, the excess nitrogen is concentrated into uric acid, a compound with five amide bonds. A series of enzyme-catalyzed reactions degrades uric acid to ammonium ion. The extent to which uric acid is de-... 

Figure 4.31 Summary diagrams of amino acid metabolism in mammary tissue, (a) Amino acid carbon interrelationships, (b) amino acid nitrogen interrelationships (from Mepham, Gaye and...

C. Role of Glutamate in the Metabolism of Amino Acid Nitrogen... 

An adult has a requirement for a dietary intake of protein because there is continual oxidation of amino acids as a source of metabolic fuel and for gluconeogenesis in the fasting state. In the fed state, amino acids in excess of immediate requirements for protein synthesis are oxidized. Overall, for an adult in nitrogen balance, the total amount of amino acids being metabolized will be equal to the total intake of amino acids in dietary proteins. 

When amino acids are metabolized, the excess nitrogen is concentrated into uric acid, a compound with five amide bonds. A series of enzyme-catalyzed hydrolysis reactions degrade uric acid—one amide bond at a time—all the way to ammonium ion. The extent to which uric acid is degraded depends on the species. Primates, birds, reptiles, and insects excrete excess nitrogen as uric acid. Other mammals excrete excess nitrogen as allantoin. Excess nitrogen in aquatic animals is excreted as allantoic acid, urea, or as ammonium salts. 

Biosynthesis of Protein. The dynamic equilibrium of body protein was confirmed by animal experiments using A/-labeled amino acids in 1939 (104). The human body is maintained by a continuous equilibrium between the biosynthesis of proteins and their degradative metabolism where the nitrogen lost as urea (about 85% of total excreted nitrogen) and other nitrogen compounds is about 12 g/d under ordinary conditions. The details of protein biosynthesis in living cells have been described (2,6) (see also Proteins). 

The nitrogen source in the medium is the amino add glutamate. There are several cations K Mn2, Cn2, Zn2, Mg2, Co2, Fe2, Ca2 Mo6. Phosphate (POi") is the major anionic component. Fumaric add is a TCA cycle intermediate and may improve metabolic balance through the catabolic pathways and oxidation through the TCA cyde. Peptone may improve growth through the provision of growth factors (amino acids, vitamins, nudeotides). 

Pyridoxal phosphate mainly serves as coenzyme in the amino acid metabolism and is covalently bound to its enzyme via a Schiff base. In the enzymatic reaction, the amino group of the substrate and the aldehyde group of PLP form a Schiff base, too. The subsequent reactions can take place at the a-, (3-, or y-carbon of the respective substrate. Common types of reactions are decarboxylations (formation of biogenic amines), transaminations (transfer of the amino nitrogen of one amino acid to the keto analog of another amino acid), and eliminations. 

Figure 11.3 is a flow model representing in extremely simple form the main relevant features of nitrogen metabolism. It is not difficult to propose a sufficient explanation why Bprot is isotopically heavier than the diet. We might expect that the net effect of transamination and deamination of amino acids is to remove isotopically lighter N (Macko et al. 1987). That is to say, we may expect that the equilibrium constant for the reaction ... 

---