Lecture 14 Catabolism of Body Proteins PDF

Lippincott’s illustrated reviews Chapter 19, Page 245 Lecture 14 Catabolism of Body Proteins 1  Specific Objectives By the end of this lecture students can be able to: Discuss the absorption and transport mechanism...

Lippincott’s illustrated reviews Chapter 19, Page 245 Lecture 14 Catabolism of Body Proteins 1  Specific Objectives By the end of this lecture students can be able to: Discuss the absorption and transport mechanism of amino acids. Explain some abnormalities in protein digestion, absorption and transport. Understand the meaning of amino acid pool and protein turnover. Explain the catabolic pathway of body proteins. 2  Abnormalities in protein digestion Individual with deficiency in pancreatic secretion (for example, due to chronic pancreatitis, cystic fibrosis, surgical removal of pancrease), the digestion and absorption of fat and protein are incomplete. This resulted in abnormal appearance of lipids (which called steatorrhea) and undigested protein in feces. 3 4  Transport of amino acid into cells Absorbed amino acids are either metabolized by liver or released into the general circulation. Free amino acids transported from extracellular fluid to the cell by active transport with the hydrolysis of ATP. At least there are seven different transport system for different amino acids. Small intestine and proximal tubule of the kidney have the common transport system for amino acids. 5 6 Cystinuria Cystinuria is an inherited autosomal recessive disease characterized by error in transport and reabsorption of of amino acids lysine, ornithine, arginine and cystine. High concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones (calculi) in the kidneys, ureters, and bladder. It is a type of aminoaciduria. "Cystine", not “Cysteine," is implicated in this disease; the cystine is a dimer of the cysteine. 7 8  Degradation of body proteins There are two major enzyme systems responsible for degrading damaged of unneeded proteins: a. The ATP-dependent ubiquitin-proteasome system of the cytosol. b. The ATP-independent degradative enzyme system of the lysosome. 9 a. Ubiquitin-proteasome proteolytic pathway: ubiquitin, a small, globular, non-enzymic protein. Unwanted proteins that selected for degradation by this method are first covalently attached to ubiquitin through amino acid lysine. Proteins tagged with ubiquitin are then recognized by a large, barrel-shaped, macromolecular, proteolytic complex called a proteasome, which functions like a garbage disposal. 10  Proteasomes degrade mainly endogenous proteins, that is, proteins that were synthesized within the cell. The proteasome unfolds, deubiquitinates, and cuts the target protein into fragments that are then further degraded to amino acids, which enter the amino acid pool. It is noteworthy that the selective degradation of proteins by the ubiquitin-proteasome complex requires energy in the form of ATP. 11 b. The ATP-independent degradative enzyme system of the lysosome: Lysosomal enzymes (acid hydrolases) degrade primarily extracellular proteins, such as: Plasma proteins that are taken into the cell by endocytosis. Cell-surface membrane proteins that are used in receptor-mediated endocytosis. 12 Chemical signals for protein degradation: Proteins have different half-lives. The half-life of a protein is influenced by the nature of the N- terminal residue. For example: Proteins that have serine as the N-terminal amino acid are long- lived, with a half-life of more than 20 hours. In contrast, proteins with aspartate as the N-terminal amino acid have a half-life of only 3 minutes. Additionally, proteins rich in sequences containing proline, glutamate, serine, and threonine are rapidly degraded. 13  Amino acid pool It is the free amino acids present throughout the body, for example, in cells, blood, and the extracellular fluids. The amino acid pool is comprised of about 90–100 g of amino acids. This pool is supplied by three sources: 1) amino acids provided by the degradation of body Proteins. 2) amino acids derived from dietary protein. 3) synthesis of nonessential amino acids from simple intermediates of metabolism. 14 Amino acid pool 15 The amino acid pool is depleted by three routes: 1) synthesis of body protein. 2) amino acids consumed as precursors of essential nitrogen- containing small molecules. 3) conversion of amino acids to glucose, glycogen, fatty acids, ketone bodies, or CO2 + H2O. In healthy, well-fed individuals, the input to the amino acid pool is balanced by the output, that is, the amount of amino acids contained in the pool is constant. The amino acid pool is said to be in a steady state, and the individual is said to in nitrogen balance. 16  Protein turnover protein turnover mean that, in the healthy adults, the total amount of protein in the body remains constant, because the rate of protein synthesis is just sufficient to replace the protein that is degraded. Hydrolysis and resynthesize of 300–400 g of body protein takes place each day. 17 18 Reference Book: Vasudevan, D. M., Sreekumari, S., and Kannan, V.., 2011. Textbook of biochemistry for medical students, 6th Edition. 19 Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 20