Kidney amino acid metabolism

Amino acid metabolism is important in all tissues/organs but especially so in the liver, intestine, skeletal muscle, adipose tissue, kidney, lung, brain, cells in the bone marrow and cells of the immune system. 

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). 

Abstract The diet of industrialised countries is usually rich in amino acids, which are partly used as a source of calories. However, metabolic alterations are observed in diseased patients and a preferential retention of Sulphurated Amino Acids (SAA) occurs during the inflammatory response. It has been demonstrated in an acute sepsis phase model in rats that the metabolism of L-Cysteine (Cys) is modified. Glutathione (GSH) concentration is greater in the liver, kidneys and other organs and Cys incorporation into proteins is higher in the spleen and lungs. In the plasma Acute Phase Proteins are released while Albumin is decreased. The pro-inflammatory cytokines such as Interleukin-1, lnterleukin-6 and TNF-a are the main initiators altering protein and amino acid metabolism. 

Glutamate dehydrogenase plays a major role in amino acid metabolism. It is a zinc protein, requires NAD+ or NADP+ as coenzyme, and is present in high concentrations in mitochondria of liver, heart, muscle, and kidney. It catalyzes the (reversible) oxidative deamination of L-glutamate to a-ketoglutarate and NH3. The initial step probably involves formation of a-iminoglutarate by dehydrogenation. This step is followed by hydrolysis of the imino acid to a keto acid and NH3 ... 

Understand amino acid metabolism in various tissues (muscle, gastrointestinal [Gl], kidney). 

An aspect of branched-chain amino-acid metabolism which may help in the control of fluxes is that the aminotransferases are very high in muscle, almost missing in liver, and have intermediate activity in the kidney, with the branched-chain a-keto acid dehydrogenase being very high in liver and kidney and less active in muscle. 

The large accumulation in the urine of the a-keto acid compared to the amino acid occurs because the kidney is adapted to effectively reabsorb amino acids, but not to reabsorb the branched-chain a-keto acids as effectively. Therefore, there is a greater spillage of the a-keto acids than the amino acids. We will see the same occurrence of large amounts of a-keto acid compared to amino acid in the urine when we look at another metabolic disease associated with aromatic amino-acid metabolism. 

In studies on the role of the adrenal hormones in amino acid metabolism, cortisone has been reported to inhibit the incorporation of glycine and alanine into liver proteins and to increase the catabolism of glycine (Clark, 1950 Sinex, 1951 Barton, 1951). Proline oxidation by kidney homogenates was depressed by adrenalectomy and restored to normal by cortisone (Umbreit and Tonhazy, 1951a, 1951b). 

Q Uric acid is the end-prod uct of amino acid metabolism in birds, land-based reptiles and many insects. In contrast to urea. It has low water solubility and Is excreted as a solid. This enables the animals to save on water and therefore weight. In humans, the purine metabolism generates urea, which is excreted via the kidneys at a rate of approximately 1 gram per day. 

The enzyme has a pH optimum of 10.0, a Qo of 52, and a turnover number of 6. The enzyme is low or absent in cat, dog, guinea pig, rabbit, pig, ox, or sheep tissues, the best source being rat liver or kidney. The limited distribution of this L-amino acid oxidase and its extremely low turnover number make it highly doubtful that this enzyme plays any major part in mammalian amino acid metabolism. 

In vivo deuterium ( H) MRS has been used to characterize amino acid metabolism, body iron content, brain and kidney metabolism and body fat utilization rates in rodents. These studies rely on the use of deuterium labelling or the existence of natural-abundance deuterium in water or lipids. For example, deuterium-labelled methionine was used to confirm the dominant contribution of the glycine/ sarcosine shuttle to the metabolism of excess methionine, while deuterium-labelled glucose was used to show that systemic glucose level influences brain... 

Some oxidases are specific for n-amino acids and others oxidize only the L-form. The physiological significance of the former is not known, since n-amino acids practically never appear in the organism. The one L-amino acid oxidase which was purified from rat kidneys contains flavin mononucleotide and has a remarkably small turnover number One enzyme molecule acts on only six molecules per minute. It is very doubtful, therefore, whether it has a significant role in amino acid metabolism. 

A metabolic cycle involving GSH as a carrier has been implicated in the transport of certain amino acids across membranes in the kidney. The first reaction of the cycle is shown below. 

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