Metabolism of Proteins

1. Metabolism of Proteins Dr. Gamal Gabr, College of Pharmacy

2. Proteins are another major food component and are found throughout the body as structural components (e.g., collagen) and as functional components, such as enzymes, receptors, transporters, and contractile elements in muscle. • Under normal conditions of dietary food intake and insulin availability, there is a dynamic balance between protein breakdown and synthesis so that individual protein levels are maintained. • Thus, there is a turnover of proteins, as old molecules are destroyed and new ones made to take their place. This emphasizes the functional importance of proteins in the body. Dr. Gamal Gabr, College of Pharmacy

3. The half-life of albumin is approximately 20 days, while some enzymes may have a half-life of only a few hours or even less. • The synthesis of protein relies on the availability of the 20 amino acids, and these can be derived from dietary proteins or are contributed by the breakdown of existing proteins within the body. Dr. Gamal Gabr, College of Pharmacy

4. The amino acids that can be made in the body are termed nonessential, while those that must be supplied in dietary protein are called essential amino acids • A deficiency in just one essential amino acid can retard growth; thus, children are particularly at risk if they have poor or restricted dietary sources of protein. Dr. Gamal Gabr, College of Pharmacy

5. Proteolysis • The hydrolysis of a protein within the body is carried out by enzymes known as proteases. • These utilize water to break the peptide bonds between amino acids, and they have a specificity for certain amino acids found within a protein sequence. • For example, the protease trypsin, active in the intestinal digestion of dietary protein, recognizes the amino acids lysine and arginine and hydrolyzes the peptide bonds on the carboxyl side of these amino acid residues. • Inside the cells and tissues of the body, proteolysis takes place within lysosome, a small cellular particle that contains many different hydrolases that break a variety of chemical bonds found within proteins, carbohydrates, lipids, and other low molecular-weight molecules

6. Proteolysis • The first step in the metabolic breakdown of amino acids is often the replacement of the –NH2group with a C=O group by the action of á-ketoglutaric acid in a process called transamination • Oxidative deamination then regenerates the á-ketoglutaric acid from the glutamic acid product of transamination. • As a net result of transamination, N(-III) is removed from amino acids and eliminated from the body. For this to occur, nitrogen is first converted to urea:

7. protein metabolism Dr. Gamal Gabr, College of Pharmacy

8. Transamination of an amino acid Dr. Gamal Gabr, College of Pharmacy

9. Urea is a solute that is contained in urine, and it is eliminated from the body via the kidneys and bladder. The α-keto acids formed by transamination of amino acids are further broken down in the citric acid (Krebs) cycle. This process yields energy, and the body’s energy needs can be met with protein if sufficient carbohydrates or fats are not available. Dr. Gamal Gabr, College of Pharmacy

10. Urea Cycle • The urea cycle takes place in the liver and involves two cellular compartments, the mitochondria and cytosol. • Initially in the mitochondria, ammonia and carbon dioxide are used along with ATP to form carbamoyl phosphate. • The carbamoyl group is transferred to a rather unusual amino acid called ornithine to form another amino acid known as citrulline. • Regulation of the urea cycle is found at the first step catalyzed by carbamoylphosphate synthase. • The molecule N-acetylglutamate can allosterically activate this enzyme. Dr. Gamal Gabr, College of Pharmacy

11. Urea Cycle Dr. Gamal Gabr, College of Pharmacy

12. The urea cycle. Ammonia is converted to carbamoyl phosphate in the presence of carbon dioxide and ATP. • The cycle begins within the mitochondria and transfers the carbamoyl group to the amino acid ornithine. • The citrulline product enters the cytosol, where it is joined with a molecule of aspartate. • The argininosuccinate product is converted to arginine and urea is liberated from this molecule in a hydrolytic step. • The enzymes involved are: • (1) carbamoylphosphate synthase, • (2) ornithine transcarbamoylase, • (3) argininosuccinate synthase, • (4)argininosuccinase, and (5) arginase.

13. Fate of Carbon Skeletons Derived from Amino Acids Dr. Gamal Gabr, College of Pharmacy

14. The fate of carbon skeletons produced from amino acids. • In transamination and transdeamination reactions, carbon skeletons from the 20 amino acids are converted into various metabolites, including pyruvate, acetyl-CoA, and various Krebs cycle intermediates. • These compounds can be used in energy generation or for ketone body synthesis or gluconeogenesis. Dr. Gamal Gabr, College of Pharmacy