Amino acid degradation urea cycle

See also Metabolic Nitrogen Balance, Transamination in Amino Acid Metabolism, Amino Acid Degradation, Urea Cycle, Ammonia Transport in the Body, De Novo Pyrimidine Nucleotide Metabolism (from Chapter 22). 

In addition to the common pathways, glycolysis and the TCA cycle, the liver is involved with the pentose phosphate pathway regulation of blood glucose concentration via glycogen turnover and gluconeogenesis interconversion of monosaccharides lipid syntheses lipoprotein formation ketogenesis bile acid and bile salt formation phase I and phase II reactions for detoxification of waste compounds haem synthesis and degradation synthesis of non-essential amino acids and urea synthesis. 

Sizer, I. W., and Jenkins, W. T. (1962). Glutamic Aspartic Transaminase from Pig Ventricles Preparation and Assay of Enzymes. Methods Enzymol 5 677. Stryer, L. (1995). Amino Acid Degradation and the Urea Cycle. In Biochemistry, 4th ed. New York Freeman. 

Most amino acid degradation takes place in tissues other than the liver. For instance, muscle uses amino acids as a source of fuel during prolonged exercise and fasting. How is the nitrogen processed in these other tissues As in the liver, the first step is the removal of the nitrogen from the amino acid. However, muscle lacks the enzymes of the urea cycle, so the nitrogen must be released in a form that can be absorbed by the liver and converted into urea. 

Glucagon stimulates the adenylate cyclase system in the liver and thereby the formation of cAMP, which gives rise to important metabolic changes, (s. tab. 3.10) Furthermore, there is a consequent decline in cholesterol synthesis, improvement in alanine membrane transport, activation of the enzymes of the urea cycle and stimulation of amino acid degradation. 

Berg, J. M., Tymoczko, J. L., and Stryer, L. 2006. Protein turnover Amino acid degradation and the urea cycle. In "Biochemistry," 6th Ed., Chapter 23. WH. Freeman and Company, New York. 

Protein degradation and the inflammatory response (p. 664) Inherited defects of the urea cycle (hyperammonemia) (p. 664) Inborn errors of amino acid degradation (p. 672)... 

In general, amino acid degradation begins with deamination. Most deamination is accomplished by transamination reactions, which are followed by oxidative deaminations that produce ammonia. Although most deaminations are catalyzed by glutamate dehydrogenase, other enzymes also contribute to ammonia formation. Ammonia is prepared for excretion by the enzymes of the urea cycle. Aspartate and CO, also contribute atoms to urea. 

Fig. 38.10. The glucose/alanine cycle. Within the muscle, amino acid degradation leads to the transfer of nitrogens to a-ketoglutarate and pym-vate. The alanine formed travels to the liver, where the carbons of alanine are used for gluconeogenesis and the alanine nitrogen is used for urea biosynthesis. This could occur during exercise, when the muscle uses blood-borne glucose (see Chapter 47).

In mammalian organisms, the ammonia produced by amino acid degradation is detoxified by conversion to urea in the liver. The metabolic pathway by which this occurs was elucidated by Krebs in 1935. Each molecule of urea contains the equivalent of two molecules of ammonia, one of which is derived from carbamoyl phosphate and one from aspartate. The urea cycle which is energetically fairly expensive is depicted in Figure 19.5. 

The ammonium ion, which is the end product of amino acid degradation, is toxic if it is allowed to accumulate. Therefore, a series of reactions, called the urea cycle, detoxifies ammonium ion (NH/) by forming urea, which is excreted in the urine. 

There is also a corresponding circulation system for the amino acid alanine. The alanine cycle in the liver not only provides alanine as a precursor for gluconeogenesis, but also transports to the liver the amino nitrogen arising in muscles during protein degradation. In the liver, it is incorporated into urea for excretion. 

Allantoin is the excretory product in most mammals other than primates. Most fish hydrolyze allantoin to allantoic acid, and some excrete that compound as an end product. However, most continue the hydrolysis to form urea and glyoxylate using peroxisomal enzymes.336 In some invertebrates the urea may be hydrolyzed further to ammonia. In organisms that hydrolyze uric acid to urea or ammonia, this pathway is used only for degradation of purines from nucleotides. Excess nitrogen from catabolism of amino acids either is excreted directly as ammonia or is converted to urea by the urea cycle (Fig. 24-10). 

Branched-chain amino acids apparently stimulate the urea cycle. Carbamoylphosphate synthetase, which channels ammonia into the urea cycle, is induced by ornithine and N-acetylglutamate as a cofactor of urea synthesis. Here, BCAA follow two modes of action (i.) they stimulate the synthesis of N-acetylglutamate via synthetase formed from glutamate and acetyl CoA, and (2.) they inhibit omithine-keto acid transferase, which is the enzyme responsible for ornithine degradation, leading to an increase in ornithine concentration. Ammonia detoxication is thus stimuiated by two regu-iatory mechanisms, (s. fig. 40.2)... 

A-13. Amino acids caii undergo oxidative degradation as a consequence of protein turnover when the diet is particularly rich in protein or when carbohydrates are not available like in starvation or in diabetes mellitus. The degrad ative pathway of every amino acid requires the separation of the amino group from the carbon skeleton. The carbon skeletons enter the Krebs cycle or are channeled into gluconeogenesis. Part of the ammonia is reused for biosynthetic purpose part is excreted directly and the rest is excreted as urea. 

To facilitate this process, enzymes of the urea cycle are controlled at the gene level. When dietary proteins increase significantly, enzyme concentrations rise. On return to a balanced diet, enzyme levels decline. Under conditions of starvation, enzyme levels rise as proteins are degraded and amino acid carbon skeletons are used to provide energy, thus increasing the quantity of nitrogen that must be excreted. 

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