Someone recently bought our

students are currently browsing our notes.


Esssay On Amino Acid Metabolism Notes

Medicine Notes > Biochemistry Notes

This is an extract of our Esssay On Amino Acid Metabolism document, which we sell as part of our Biochemistry Notes collection written by the top tier of Oxford students.

The following is a more accessble plain text extract of the PDF sample above, taken from our Biochemistry Notes. Due to the challenges of extracting text from PDFs, it will have odd formatting:

Outline the overall strategy of amino acid metabolism in man. Some amino acids, in particular alanine, glutamine, citrulline and the branched chain amino acids (leucine, isoleucine and valine) play specific roles in normal metabolism. Define these roles and consider how they are integrated into the overall control of energy metabolism Importance of amino acids Amino acids are an intergral part of the diet and their main role is in the synthesis of proteins and other nitrogenous compounds such as nucleotide bases. The main supply of amino acids comes from the digestion of dietary proteins or from the breakdown of proteins within the cell. Unlike fatty acids and glucose, excess amino acids cannot be stored or excreted, so are used as a metabolic fuel. In these situations the alpha amino group is removed and the carbon skeleton is converted into a specific metabolic intermediate depending on the type of amino acid. Gluconeogenic amino acids are converted into glucose through gluconeogenesis via metabolic intermediates such as pyruvate or TCA cycle intermediates. An example of a gluconeogenic amino acid is alanine which via pyruvate is converted into glucose. However the carbon skeleton of ketogenic amino acids are broken into acetyl coA or acetoacetyl coA both which give rise to ketone bodies or fatty acids. Examples of such amino acids are leucine and lysine. Therefore amino acids have a range of fates depending on the location of where they are being absorbed. They can either be used to synthesise body proteins or can be incorporated with other types of molecules to form hormones, neurotransmitters and pigment molecules. They can also be converted into glucose or fatty acids which can then be stored as glycogen or triglycerides. Finally they can be oxidised to release energy during periods of starvation or fasting. Some amino acids can be endogenously synthesised or recycled from cell proteins in the body but those that can't known as essential amino acids must be supplied from the diet. These amino acids include arginine, histidine, isoleucine, leucine, threonine, lysine, methionine, phenylalanine, tryptophan and valine. If there is deficiency in any of these amino acids the body has a negative nitrogen balance which means more nitrogen is excreted than ingested and this often impairs growth and important protein synthesis in the body. Around 70 to 100 grams of protein is ingested and digestion of these proteins initiates in the stomach where the acid secreted by parietal cell via the K-H-ATPase pump denatures the protein. Also secreted by cells in the stomach are zymogens such as pepsinogen which

spontaneously cleaves itself into an active form in the acidic environment of the lumen. Digestion of the proteins continues further in the lumen of the small intestine via pancreatic enzymes and by enzymes embedded in the cells of the small intestine such as enterokinase. The action of these enzymes which vary in their specificity results in a mixture of free amino acids or oligopeptides that is then transported into intestinal cells from the lumen and released into the blood for absorption by other tissues. 75% of the amino acids entering the portal circulation from the GI tract after a meal are metabolised in the liver and the remaining 25% is available in the general circulation. How they are amino acids metabolised in peripheral cells?
The first stage of amino acid metabolism is transamination and is catalysed by transaminases which use the cofactor pyridoxal-phosphate (derived from vitamin pyridoxine) to transfer an amino group from the amino acid to an alpha ketoacid. In peripheral tissues catabolism of amino acids involves the alpha ketoacid, alpha ketoglutarate, which is aminated to form glutamate, which is also an amino acid. The remaining carbon skeleton of the deaminated amino acid is then used as an energy substrate. The overall reaction proceeds as below: Amino acid + alpha-ketoacid ??
alpha-ketoacid + amino acid The glutamate can either be used in protein synthesis or can be involved in other transamination reactions which regenerate the alpha ketoglutarate and synthesise specific amino acids. However to discard the amino group in glutamate generated from the transamination reactions glutamine is formed which is then transported to the liver via the circulation. The key enzyme in the removal of the ammonia rather than transferring it to another molecule from glutamate is glutamate dehydrogenase which uses the cofactor NAD+
to catalyse the reaction where the nitrogen atom in glutamate is converted into free ammonium by oxidation deamination. This reaction converts glutamate into alpha-ketoglutarate, which is one of the TCA cycle intermediates. To prevent the released ammonia accumulating into the cell and diffusing into the circulation, glutamine synthetase which has a high

affinity for ammonia catalyses the reaction that binds ammonia to another glutamate to form glutamine. Role of glutamine As mentioned above one of the main roles of glutamine is to transport waste ammonia in a non toxic form to the liver or kidney for excretion. It can also be transported to the intestine where it is used as a metabolic fuel. Free ammonia in the circulation is extremely toxic especially to the brain so the free ammonia generated in the tissues binds to glutamate using the energy from the hydrolysis of ATP to form glutamine. The importance of glutamine is portrayed in blood plasma concentrations; for ammonia it is around 10-20 micromoles/litre whereas for glutamine the concentration is between 400600 micromoles per litre. The majority of the glutamine enters the periportal cells of the liver which contains the enzyme glutaminase and this catalyses the hydrolysis reaction which converts glutamine into glutamate and releases ammonia. The glutamate released can be used in protein synthesis or can take part in transamnation reactions. However to remove the ammonia in glutamate, like in peripheral cells the enzyme glutamate dehydrogenase is used. Some of the ammonia released from glutamine and glumate can be used in the biosynthetic reaction of nitrogenous compounds, however the majority is converted into urea which is generated via the urea cycle which occurs in the periportal cells and is excreted in the urine. The first step in the urea cycle occurs in the mitochondria and involves the formation of carbamyl phosphate from the reaction of free NH3, HC03- and 2 ATP. This reaction is catalysed by carbamyl phosphate synthetase which is the committed point of entry of NH3. However this enzyme is only active in the presence of Nacetylglutamate which is produced from the reaction of glutamate and acetyl coA. The carbamyl group is then transferred to ornithine to from citrilline. The citrulline is then transported into the cytoplasm where it condenses with aspartate which also contains an amino group to form arginosuccinate. This molecule is then cleaved to form arginine and fumerate. The fumerate enters the TCA cycle where is oxidised to release energy and reduced NADH. However the arginine is hydrolysed to form urea regenerate ornithine. The ornithine is transported back into the matrix of the mitochondria which allows the urea cycle to continue. The urea is transported to the kidney where it is excreted. Deficiencies of enzymes in the urea cycle such as ornithine transcarbamolyase defciency leads to the build up of ammonia leading to hyperammonemia and this eventually results in coma.

Buy the full version of these notes or essay plans and more in our Biochemistry Notes.