Nitrogen metabolism amino acid catabolism

The nitrogen contained in the amino acids is usually disposed of through the urea cycle. One of the early, if not the first, steps in amino acid catabolism involves a transamination using oxaloacetate or a-ketoglutarate as the amino-group acceptor. This converts the amino acid into a 2-keto acid, which can then be metabolized further. 

Nitrogen ranks behind only carbon, hydrogen, and oxygen in its contribution to the mass of living systems. Most of this nitrogen is bound up in amino acids and nucleotides. In this chapter we address all aspects of the metabolism of these nitrogen-containing compounds except amino acid catabolism, which is covered in Chapter 18. 

The liver also plays an essential role in dietary amino acid metabolism. The liver absorbs the majority of amino acids, leaving some in the blood for peripheral tissues. The priority use of amino acids is for protein synthesis rather than catabolism. By what means are amino acids directed to protein synthesis in preference to use as a fuel The K jyj value for the aminoacyl-tRNA synthetases is lower than that of the enzymes taking part in amino acid catabolism. Thus, amino acids are used to synthesize aminoacyl-tRNAs before they are catabolized. When catabolism does take place, the first step is the removal of nitrogen, which is subsequently processed to urea. The liver secretes from 20 to 30 g of urea a day. The a-ketoacids are then used for gluconeogenesis or fatty acid synthesis. Interestingly, the liver cannot remove nitrogen from the branch-chain amino acids (leucine, isoleucine, and valine). Transamination takes place in the muscle. 

The initial step of amino acid catabolism frequently involves the loss of the amine nitrogen to yield a carbon skeleton in the form of a keto acid, either as a result o transamination or by deamination. In general, energy is derived from amino acids bj the oxidation of the carbon skeletons after entry into the intermediary metabolic pathways. 

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. 

Effect on Protein Metabolism, Corticoid hormones affect various steps of protein metabolism amino acid penetration in the cells, intracellular biosynthesis of amino acids from small precursors, protein synthesis, and protein catabolism. In discussing the effect of corticoid hormones on protein synthesis, it is necessary to distinguish between the effects of the glucocorticoid on muscle and liver. The injection of Cl 1-oxygenated corticosteroid increases the excretion of urinary nitrogen, with loss of tissue nitrogen (e.g., in heart and kidney) [51]. 

In considering amino acid catabolism, one must distinguish the catabolism of the carbon chain from that of the nitrogen moiety. The breakdown of the carbon chain of the amino acids yields carbon units that can be used in carbohydrate metabolism, acetate metabolism, or the metabolism of single carbon units. The fate of the carbon units of the individual amino acids has been discussed in other sections of this book, and only a synopsis of the results will be presented here. The carbon skeletons of isoleucine, phenylalanine, threonine, tryptophan, valine, histidine, alanine, arginine, aspartic acid, glycine, proline, glutamic acid, and hydroxyproline are ultimately converted to pyruvic acid. 

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). 

A protein that is unduT7 rich in the ten essential amino acids would not provide sufficient nitrogen for other metabolic processes without obligatory catabolism of the essential amino acids. Thus, the proportion of the total nitrogen intake that essential amino acids form indicate how a given protein fulfills nutritional requirements for proteins. This proportion, the E/T ratio (54), indicative of the amount of protein nitrogen supplied by essential amino acids, is (in g of essential amino acids per g of nitrogen)... 

Anno acid catabolism is part of the larger process of whole body nitro gan metabolism. Nitrogen enters the body in a variety of compounds present in food, the most important being amino acids contained in detary protein. Nitrogen leaves the body as urea, ammonia, and other products derived from amino acid metabolism. The role of body proteins in these transformations involves two important concepts the amino acid pool and protein turnover. 

The anaerobic mode of protein utilization is entirely possible in theory and in practice. Oxygen is not required for protein and nitrogen catabolism until the final stages of amino acid deamination have been reached. Complete anaerobic catabolism of proteins and nitrogen compounds (to the point where the final products C02, HjO and NH3 appear) has been known for a long time in prokaryotic organisms, but in eukaryotes only in parasitic worms, which are obligate anaerobes (von Brand, 1946). However, in recent decades, anaerobic metabolism of proteins has been found in some aquatic... 

In addition to being incorporated into tissue proteins, amino acids, after losing their nitrogen atoms by deamination and/or transamination, may be catabolized to yield energy or to form glucose. Conversely, the nonessential amino acids may be synthesized from carbohydrate metabolism intermediates and ammonia or from essential amino acids. This section is devoted to the mechanisms of such metabolic processes and their interrelationships with carbohydrate and lipid metabolic pathways. 

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). 

Although the liver is crucial in protein synthesis, it is of equal importance in amino acid metabolism and degradation. This is evidenced by the high daily turnover of amino acids, and the high proportion of amino acids that are recycled and reconstituted into new protein molecules. Over 30 g of protein are irreversibly catabolised (and hence lost) daily. The nitrogen released from the complete catabolism of amino acids can be removed by a variety of routes, but the principal... 

The indication for administering BCAA in patients with hepatic encephalopathy to compensate amino-acid imbalance was proposed by J.E. Fischer et al. in 1974, and implemented parenterally. However, oral application of BCAA for an adequate treatment period also has beneficial effects on cirrhosis and HE (7.) improvement in protein tolerance and the nutritional condition, (2.) improvement in cerebral functions (II8, 122), probably due to an amelioration of liver function, (2.) stimulation of ammonia detoxification with a positive nitrogen balance (118), (4.) reduction in or normalization of AAA levels, and (5.) promotion of glutamine synthesis with a favourable effect on the cells of the immune system and on renal function. By means of BCAA, it was possible to prolong the survival time and delay the occurrence of liver failure in rats with CC -induced cirrhosis. (123, 126) However, there are diverging results, which need further clarification. In principle, the use of BCAA is considered to be a necessary form of supplementary treatment for catabolic metabolism in cirrhosis (124,125, 127, 128, 130-132), in (also latent) HE and after curative resection of hepatocellular carcinoma. (I2l) (s. p. 280)... 

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