Amino acids metabolic processes

Pyridoxal phosphate is the coenzyme for the enzymic processes of transamination, racemization and decarboxylation of amino-acids, and for several other processes, such as the dehydration of serine and the synthesis of tryptophan that involve amino-acids (Braunstein, 1960). Pyridoxal itself is one of the three active forms of vitamin B6 (Rosenberg, 1945), and its biochemistry was established by 1939, in considerable part by the work of A. E. Braunstein and coworkers in Moscow (Braunstein and Kritzmann, 1947a,b,c Konikova et al 1947). Further, the requirement for the coenzyme by many of the enzymes of amino-acid metabolism had been confirmed by 1945. In addition, at that time, E. E. Snell demonstrated a model reaction (1) for transamination between pyridoxal [1] and glutamic acid, work which certainly carried with it the implication of mechanism (Snell, 1945). 

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. 

Mitochondria play a central role in a variety of biological processes, including ATP synthesis, steroid hormone synthesis, the urea cycle, lipid and amino acid metabolism, and cellular Ca2+ homeostasis. Ca2+ is an essential regulator of vital processes, such as secretion, motility, metabolic control, synaptic plasticity, proliferation, gene expression and apoptosis. Therefore, the location, amplitude,... 

Protein degradation and amino acid metabolism are highly elevated in the diabetic, because the stimulatory effect of insulin on protein synthesis is nonexistent and the relative excess of glucagon and glucocorticoids causes protein breakdown to continue. Indeed, muscle wasting is a cardinal symptom of the untreated diabetic. Insulin also inhibits amino add release into the bloodstream, and this may be a reason a moderate rise in plasma amino add levels is observed in the diabetic. Such increased amino adds are largely of the branched-chain type, and alanine levels are in fact lower than normal. Nevertheless, alanine uptake by the liver is twice that of the normal individual, and it continues to be a major actor in the gluconeogenesis process. 

Ammonia is found in the environment as the result of natural and industrial processes. It is released into the environment by the breakdown of organic wastes, and it is a constituent of the soil, the atmosphere, and bodies of water. Ammonia is also a key intermediate in the nitrogen cycle and is a product of amino acid metabolism (WHO 1986). Anhydrous ammonia is used in the production of nitric acid, explosives, synthetic fibers, and fertilizers (Budavari 1989). It is used as a refrigerant as a corrosion inhibitor in the purification of water supplies in steel production as a catalyst for polymers as a preservative for latex and in the production of nitrocellulose, urea formaldehyde, sulfite cooking liquors, and nitroparaffins (ACGIH 1991 Lewis 1993). Ammonium hydroxide (10-35% ammonia) is a major constituent of many cleaning solutions. Ammonia... 

In contrast to zinc, the crucial role of Fe in the bioenergetics of carbon (C) and N metabolism is well recognized (e.g., Morel et al., 1991 Sunda, 1989). Substantial amounts of Fe are required in both photosynthetic and respiratory electron transport chains (e.g., Raven, 1988), the synthesis of chlorophyll (Chereskin and Castelfranco, 1982), and the assimilation ofNOj. Theoretical calculations based on Fe utilization efficiencies and cellular metabolic Fe demands, predict that phytoplankton growing on NOJ require 60% more Fe than those growing on NH (Raven, 1988, 1990), and greater cellular Fe requirements for NO growth have indeed been demonstrated for laboratory cultures of diatoms (Maldonado and Price, 1996). The extra Fe is needed to reduce NO to NH4 before it can be incorporated into amino acids. This process requires the assimilatory enzymes nitrate reductase (requires one... 

Nyhan, W. L. (Ed.), 9M. Abnormalities in Amino Acid Metabolism in Clinical Medicine. Appleton-Century-Crofts. Historical aspects and the process of discovery... 

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 urea cycle is the most important process in biological ammonia detoxication, (s. pp 57, 266) (s. figs. 3.12, 3.13) It is directly linked with amino-acid metabolism and thus also with NH2 donors and precursors through specific amino acids and transamination processes. Here, the major transamination processes are those involving glutamate and oxalacetate as well as a-ketoglutarate and aspartate. 

However, it should be recognized that the reverse reaction is a key anapleurotic process linking amino acid metabolism with TCA cycle activity. 

Amino acids, peptides, and proteins play crucial roles in virtually all biological processes, with amino acids being the basic structural units of proteins. Many genetic mutations result in the incorporation into proteins of amino acids that may alter rates of synthesis, secretion, or metabolism of the proteins and their function. In addition, there are a large number of inherited abnormalities of amino acid metabolism (see Chapter 55). 

Protein turnover is not completely efficient in the reutilization of amino acids. Some are lost by oxidative catabolism, while others are used in synthesis of non-protein metabolites. For this reason, a dietary source of protein is needed to maintain adequate synthesis of protein. During periods of growth, pregnancy, lactation, or recovery from illness, supplemental dietary protein is required. These processes are affected by energy supply and hormonal factors. An overview of amino acid metabolism is presented in Figure 17-1. 

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... 

Processes occurring inside the mitochondrial matrix include pyruvate oxidation, fatty acid oxidation, amino acid metabolism, and the citric acid cycle. Furthermore, respiratory proteins are bound to the inner membrane, so the density of cristae corresponds to the respiratory activity of a cell. For example, mitochondria in heart muscle cells (high rates of respiration) are densely packed with cristae, whereas mitochondria in liver cells (low rates of respiration) have more sparsely distributed cristae. 

Concentrations of various carboxylic acids in human body fluids reflect some of the major metabolic processes of the body. These metabolites apparently originate from lipid and amino acid metabolism the major metabolic defects are frequently associated with unbalanced concentrations of these acidic substances. One of the most widely occurring conditions of this kind is ketoacidosis in diabetic disease high concentrations of the so-called ketone bodies (3-hydroxybutyric acids, acetoacetic acid and others) are the traditional hallmarks of ketoacidosis. Many additional acidurias were discovered (particularly during the last 15 years) in major part due to the availability of GC and GC/MS techniques. Acidurias are among the serious medical conditions that are usually a result of genetic aberration (enzyme deficiencies), but environmental factors or nutritional deficiency could occasionally be involved. These conditions are characterized by either (a) drastically enhanced excretion of normal metabolic intermediates, or (b) excretion of unusual metabolites that are produced from the accumulated intermediates via alternate biochemical pathways. Many acidemic conditions have now been documented in the literature, and the role of GC in such medical discoveries has been adequately stressed in the recent reviews of Jellum [15] and Tanaka and Hine [373]. 

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