Free Amino Acid Metabolism Essay Sample
In mammals, the degradation of amino acids takes place in the liver. Within the body, body tissues have the ability of synthesis of amino acids, amino acids remodelling and conversion of non-amino acids carbon skeletons into amino acids. Nitrogen metabolism within the body takes place in the liver. In cases of toxic nitrogen, elimination occurs through the process of deamination, transamination, and urea formation. During this process, conservation of carbon skeletons as carbohydrates occurs through fatty acids synthesis. Amino acids fall into three categories: glucogenic, ketogenic, or glucogenic and ketogenic. Glucogenic amino acids are those that facilitate the production of pyruvate or TCA cycle intermediates.
All amino acids except lysine and leucine are least partly glucogenic. Lysine and leucine are the only amino acids that are solely ketogenic to giving rise only to acetylCoA or acetoacetylCoA, neither of which can bring about net glucose production. Amino acids comprising isoleucine, phenylalanine, threonine, tryptophan, and tyrosine produce glucose and fatty acids. They are thus categorized as being glucogenic and ketogenic. It is also important to note that during starvation, the number of carbon skeleton reduces. Carbon skeleton is broken down to produce energy. Oxidation takes place to release CO2 and H2O.
The Metabolism and Synthesis of Amino Acids
According to Mosby’s Medical dictionary, Amino acid metabolism is the process whereby the body uses the consumed protein foods to make tissue proteins. This takes place alongside with the breakdown of tissue proteins in energy production. Food proteins are broken down into amino acids before absorption into the bloodstream and being used up min the body cells to form new proteins. The liver enzymes break down into keto acids and urea converts excess amino acids. Keto acids are a source of energy in the citric acid cycle. They can also be converted into glucose or fats and stored in the body. Urea is secreted in urine and sweat. Stimulation of protein formation is triggered by insulin and androgen growth hormones. Adrenal cortical hormone causes the breakdown of body proteins. Diseases affecting protein metabolism include homocystinuria, liver disease, maple sugar urine disease, and phenylketonuria.
During the synthesis of amino acids, a nitrogen source is essential. In animals, glutamate and glutamine are the key players. According to Stryer (1995), Majority of amino acids come from transamination reaction where the amino acid group transfers glutamate to a α-ketoacid acceptor. Glutamate is synthesized from ammonia and α-ketoglutarate by the process of glutamate dehydrogenase.
Plants and bacteria have the ability to synthesize all the twenty amino acids. Humans can only synthesize nine amino acids. These nine amino acids evolve from the human diet. They are commonly termed as essential amino acids. They are Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and Valine. Arginine is essential in infants. Deficiency of one of the essential amino acids causes a negative nitrogen balance. This means that more proteins are degraded than they are synthesized and more nitrogen is excreted than it is ingested. The other amino acids that humans are not able to synthesize are non-essential amino acids and they include Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine, and Tyrosine. Non-essential amino acids are synthesized using simple pathways while the biosynthesis of essential amino acids is complex. Biosynthesis of non-essential amino acids takes place in either a one-step reaction or multiple step reactions (Wendisch, 2007).
Pyruvate + glutamate ⇔ alanine + α-ketoglutarate
Oxaloacetate + glutamate ⇔ aspartate + α-ketoglutarate
Aspartate + NH4+ + ATP → asparagine + AMP + PPi + H+
Phenylalanine + O2 + NADPH + H+ → tyrosine + NADP+ + H20
Glutamate →→→ proline and arginine
3-phosphoglycerate →→→ serine, cysteine and glycine
Most Amino acids humans consume are in the form of proteins, which during digestion are broken down into amino acids. The digestion of proteins takes place in the gut. Monomers, which are free amino acids pass through the wall and into the blood stream and are taken up the cell. Excess amino acids are converted into glucose, fatty acids and ketone bodies. Degradation of amino acids takes place in three stages. The first stage is deamination of amino acids, which are converted into ammonia or amino group of aspartate. In the second stage, there is the incorporation of ammonia or aspartate nitrogen into urea for excretion. In the last stage, there is the conversion of the AA carbon skeletons to the common intermediates. The AA carbon skeletons are the keto acids that result from deamination.
Deamination is the removal of amine group of cells from a molecule. This reaction is catalyzed by enzymes known as deaminase. In the human body, deamination takes place in the liver. During the process of deamination, amino acids are broke down. The amino group present is removed from the amino acid and converted into ammonia. The rest of the amino acids mainly comprising of carbon and hydrogen is recycled and oxidized to release energy. Since ammonia is toxic in the human system, the enzymes convert it into urea and uric acid by adding carbon dioxide molecules into it. Urea and uric acid then diffuse into the blood and are later excreted in urine.
Deamination is also an oxidative reaction that occurs under aerobic conditions in the liver. During oxidative deamination, amino acids are converted into corresponding keto acids by removing the amine group as ammonia and replacing it by the ketone group. The ammonia eventually goes into the urea cycle. Oxidative deamination takes place in the presence of glutamic acid since glutamic acid is the end product of many transamination reactions. The glutamate dehydrogenase is under the control of ATP and ADP. During chemical reactions, ATP acts as an inhibitor while ADP is an activator; it speeds up the rate of the reaction.
According to Michael King (1995), there are several deamination reactions that take place in DNA. Spontaneous deamination is the process of hydrolysis reaction of cytosine into uracil releasing ammonia in the process. This process occurs in vitro through the use of bisulphate, which converts cytosine. In DNA, deamination is corrected by removing uracil with uracil-DNA glycosylase, which results in an abasic site. Enzymes recognize this site by breaking down phosphodiester bond in the DNA enhancing the repair lesion and replacement of cytosine. DNA polymerase performs this replacement through nick translation. DNA ligase then forms a phosphodiester bond to seal the resulting nicked duplex product.
Spontaneous deamination of 5-methylctosine results in thymine and ammonia. This is a single nucleotide mutation. In DNA, correction of this reaction is impossible as the repair mechanisms do not recognize thymine as erroneous, unless there is an effect in the gene functioning the mutation persists. In Guanine, spontaneous deamination ends in the formation of xamine. Xanthine pairs with thymine instead of cytosine resulting in a post-replicative transition mutation where the actual G-C base pair transforms into an A-T base repair. During its correction alkyladenine glycosylase reaction takes place. Deamination of adenine results in formation of hypoxanthine. Hypoxanthine carries out its repairs with cytosine instead of thymine. Final out come is a post-replicative transition mutation where the original A-T base repair transforms into a G-C base repair.
The urea cycle takes place within the liver. As the liver cleans blood, it releases ammonia (NH4+) from the body in form of urea. Urea is excreted from the body through the kidneys in urine. Ammonia originates from the breakdown of amino acids. Break down of amino acids takes when there is an excess of amino acids present for direct use by a process known as deamination (The Bello Lectures, 2002). Deamination of amino acids results in the production of ammonia (NH3). This mostly takes place in western countries, where there is consumption of lots of proteins.
Ammonium ions are always at equilibrium with 1% free ammonia at psychological PH. The toxic state of ammonium salts causes vomiting, convulsions, and in cases where the blood concentration exceeds 0.25mM, it leads to a coma and at times to death. The liver contains a system of carrier molecules and enzymes, which converts ammonia into urea. This process is the urea cycle. The overall urea formation reaction is:
2 Ammonia + carbon dioxide + 3ATP ---> urea + water + 3 ADP
One amine group occurs through oxidative deamination of glutamic acid while the other comes from oxidation of aspartic acid. Brosnan (2000) says, Aspartic acid is regenerated from fumatic acid produced in the urea cycle. Carbon atoms come from carbon dioxide. Transportation of carbon and nitrogen atoms takes place through the amino acid ornithine. Urea is then formed from arginine. Hydrolysis of arginine forms urea and ornithine through arginase enzyme. Other reactions of urea cycle regenerate arginine from ornithine. Carbamoyl group of carbamolyl phosphate transfers to the orthinine forming citrulline, a reaction catalyzed by ornithine transcarbamoylase enzyme (Malandro & Kilberg, 1996).
Consequently, argininosuccinate synthetase catalyses the condensation of citrulline and aspartate. Splitting of ATP in AMP and pyrophosphate and hydrolysis of the generated pyrophosphate produces energy required for formation of argininosuccinate. Finally, argininosuccinate in arginine and fumarate splits up with the aid of argininosuccinase enzyme making the amine group of phosphate transfer to form arginine by the reactions. The remaining carbon skeleton of aspartate is left over in the form of fumarate. Formation of Carbamoyl phosphate takes place in the mitochondria of the cell from CO2, H2O, NH4+ and ATP. The reaction is:
CO2 + NH4+ + 2 ATP + H2O→Carbamoyl Phosphate + 2ADP + Pi + 3H+
Therefore, coupling of the urea cycle and the citric acid cycle occurs through the intermediate fumarate (Malandro & Kilberg, 1996).
In conclusion, Amino acid metabolism is important for the normal functioning of the pancreatic β-cell. Key amino acids like alanine and glutamine regulate the β-cell function and secretion of insulin. Amino acids confer their regulatory functions in a complex way involving the mitochondria metabolism. L-Glutamine metabolism is essential in stimulus secretions especially in the presence of glucose and for the production of glutathione. Biosynthesis of amino acids is often regulated highly such that synthesis takes place when supplies are low. In cases where the final product has high concentration, there is inhibiting of the activity of enzymes, which function early in the pathway.