Excretion nitrogen, amino acid metabolism

One of the major products of amino acid metabolism is ammonia (NLI3), a molecule known to be highly toxic to higher organisms. In the liver, ammonia and carbon dioxide are used to produce a water-soluble form of nitrogen, urea, via the urea cycle. The liver passes this urea to the blood, which carries it to the kidneys to be filtered out and excreted in the urine. Since one function of the kidney is to collect and excrete urea, increases in the concentration of this compound in the blood are an indicator of poor kidney function. Since urea is formed in the liver, low blood urea nitrogen is often the consequence of impaired liver function due to disease or as the result of infection (hepatitis). 

The amino acid molecules that are immediately available for use in metabolic processes are referred to as the amino acid pool. In animals, amino acids in the pool are derived from the breakdown of both dietary and tissue proteins. Excreted nitrogenous products such as urea and uric acid are output from the pool. Amino acid metabolism is a complex series of reactions in which the amino acid molecules required for the syntheses of proteins and metabolites are continuously being synthesized and degraded. Depending on current metabolic... 

Magnesium also plays an essential role in protein and amino acid metabolism. The synthesis of proteins in rat liver decreased during magnesium deficiency (Sharma, 1975), and magnesium-deficient rats also exhibited aminoaciduria and increased excretion of total urinary nitrogen (Mazzacco et al., 1966). 

Amino acids derived from dietary or body proteins are also potential fuels that can be oxidized to acetyl CoA, or converted to glucose and then oxidized (see Fig. 2). These oxidation pathways, like those of fatty acids, generate NADH or FAD(2H). Ammonia, which can be formed during amino acid oxidation, is toxic. It is therefore converted to urea in the liver and excreted in the urine. There are more than 20 different amino acids, each with a somewhat different pathway for oxidation of the carbon skeleton and conversion of its nitrogen to urea. Because of the complexity of amino acid metabolism, use of amino acids as fuels is considered separately in Section Seven, Nitrogen Metabolism. 

The liver is the major site of amino acid metabolism in the body and the major site of urea synthesis The liver is also the major site of amino acid degradation. Hepatocytes partially oxidize most amino acids, converting the carbon skeleton to glucose, ketone bodies, or CO2. Because ammonia is toxic, the liver converts most of the nitrogen from amino acid degradation to urea, which is excreted in the urine. The nitrogen derived from amino acid catabolism in other tissues is transported to the liver as alanine or glutamine and converted to urea. 

The output of N from the body is largely in the urine and faeces, but significant amounts may also be lost in sweat and shed skin cells — and in longer-term studies the growth of hair and nails must be taken into account. Obviously, any loss of blood or tissue will also involve a loss of protein. Although the intake of nitrogenous compounds is mainly protein, the output is mainly urea (section 9-3.1.4), though small amounts of a number of other products of amino acid metabolism are also excreted, as shown in Table 9.1. 

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 amino acids are required for protein synthesis. Some must be supplied in the diet (the essential amino acids) since they cannot be synthesized in the body. The remainder are nonessential amino acids that are supplied in the diet but can be formed from metabolic intermediates by transamination, using the amino nitrogen from other amino acids. After deamination, amino nitrogen is excreted as urea, and the carbon skeletons that remain after transamination (1) are oxidized to CO2 via the citric acid cycle, (2) form glucose (gluconeogenesis), or (3) form ketone bodies. 

The urea cycle is essential for the detoxification of ammonia 678 Urea cycle defects cause a variety of clinical syndromes, including a metabolic crisis in the newborn infant 679 Urea cycle defects sometimes result from the congenital absence of a transporter for an enzyme or amino acid involved in the urea cycle 680 Successful management of urea cycle defects involves a low-protein diet to minimize ammonia production as well as medications that enable the excretion of ammonia nitrogen in forms other than urea 680... 

Urea is a colorless, odorless crystalline substance discovered by Hilaire Marin Rouelle (1718—1779) in 1773, who obtained urea by boiling urine. Urea is an important biochemical compound and also has numerous industrial applications. It is the primary nitrogen product of protein (nitrogen) metabolism in humans and other mammals. The breakdown of amino acids results in ammonia, NH3, which is extremely toxic to mammals. To remove ammonia from the body, ammonia is converted to urea in the liver in a process called the urea cycle. The urea in the blood moves to the kidney where it is concentrated and excreted with urine. 

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). 

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