Protein Digestion PDF - Babylon Medical College

Babylon Medical College Clinical Biochemistry Protein Digestion Second stage Lectures 1 Prof D. Thana Mohammed E mail [email protected]  Objective 1.Describe the main the process of Metabolism with anabolism and catabolism 2. Describe Pr...

Babylon Medical College Clinical Biochemistry Protein Digestion Second stage Lectures 1 Prof D. Thana Mohammed E mail [email protected]  Objective 1.Describe the main the process of Metabolism with anabolism and catabolism 2. Describe Process of digestion of protein and role of HCL on protein metabolism 3. Describe the main Proteolytic enzymes and theirs role on protein metabolism 4.Study the main clinical disorder associated with protein metabolism  Protein a class of nitrogenous organic compounds which have large molecules composed of one or more long chains of amino acids that consists of amino acid residues joined by peptide bonds. and are an essential part of all living organisms, especially as structural components of body tissues such as muscle, hair, etc., and as enzymes and antibodies Amino acid structure General structural formula for α-amino acids. There are 20 different R groups in the commonly occurring amino acids.  Biological Roles of Proteins (examples ) 1. Catalysis (enzymes) 2. Transport (e.g., hemoglobin - O2 transport in blood; transport of ions across cell membranes) 3. Storage (e.g., myoglobin - oxygen storage in muscle; Ferritin storage of iron 4. Coordinated motion (e.g., in muscle like actine and myosin,) 5. Mechanical support (e.g., collagen) 6. Protection (e.g., immune system - antibodies; blood clotting proteins) 7. Regulation and communication (e.g., hormones, receptors,) Globular and Fibrous Proteins Globular Proteins Molecule forms a coiled shape (globule) Hydrophobic amino acid located inside centre of molecule away from water Only hydrophilic amino acid are exposed outside the molecule so globular proteins are soluble Globular proteins have roles in metabolic reactions: – Enzymes - catalyse metabolic reactions – Haemoglobin - binds to oxygen to transport it around body  Fibrous Proteins Polypeptides form long chains running parallel to each other These chains are linked by disulphide cross bridges – making the proteins very stable and strong Fibrous proteins have Structural functions: – Keratin in skin and hair – Collagen - found in bone, cartilage, tendons and ligaments for tensile strength  Metabolism of protein Metabolism consists of anabolism (the buildup of substances) and catabolism (the breakdown of substances). The term metabolism is commonly used to refer specifically to the breakdown of food and its transformation into energy. Dr.Saba 9 Amino acid catabolism is part of the larger process of the metabolism of nitrogencontaining molecules. Nitrogen enters the body in a variety of compounds present in food,the most important being amino acids contained in dietary protein. Nitrogen leaves the body as urea, ammonia, and other products derived from amino acid metabolism. Digestion of protein  The dietary proteins are denatured on cooking and therefore more easily digested by enzyme called peptidase an enzyme that hydrolyzes simple peptides these enzymes are hydrolases (class 3 enzymes) Depending on the source of peptidases, the protein digestive process can be divided into 3 phases: 1-Gastric 2-Pancreatic 3-Intestinal Peptidase are Proteolytic enzymes are secreted as inactive form called zymogens which are converted to their active form in the intestinal lumen. This would prevent autodigestion of the secretory acini.  Protein digestion in the stomach. Entry of dietary protein into the stomach stimulates the gastric mucosa to secrete gastrin which is a peptide hormone primarily responsible for secretion of hydrochloric acid (HCl) into the stomach. HCI secreted by the parietal cells reduces the pH of stomach to 1-2 The acidic gastric juice is both an antiseptic agent, killing most bacteria and other foreign cells, and a denaturating agent, unfolding globular proteins. Gastric Digestion of protein Activation of pepsine Pepsin is an endopeptidase, Pepsin catalyses hydrolysis of the bonds formed by carboxyl groups of Phe, Tyr, Trp and Met.  Pancreatic Digestion of Proteins Pancreatic juice contains the important endopeptidases,namely Trypsin, Chymotrypsin, Elastase and Carboxypeptidase. These enzymes are also secreted as zymogens (trypsinogen, chymotrypsinogen and pro-elastase), so that the pancreatic acinar cells are not autolysed. All the three are serine proteases, i.e. the active centers of these enzymes contain serine residues.The part of the enzyme where the substrate binds is called the active site (since that's where the catalytic “action” happens). A substrate enters the active site of the enzyme. The optimum pH for the activity of pancreatic enzymes (pH 8) is provided Bicarbonate [HCO3 secreted by the pancreas in response to the intestinal hormone secretin, raises the intestinal pH.) The secretion of pancreatic juice is stimulated by the peptide hormones, Cholecystokinin  Pancreatic Digestion of Proteins Exopeptidase: An enzyme that catalyzes the cleavage of the terminal (last) or next- to-last peptide bond from a polypeptide or protein, releasing a single amino acid or dipeptide. By contrast, an endopeptidase catalyzes the cleavage of then internal peptide bonds within a polypeptide or protein Action of protease Endopeptidases (cleave internal peptide bonds) Exopeptidases Carboxypeptidases Aminopeptidases  Pancreatic proteases have different substrate specificity with respect to peptide bond cleavage. Trypsin arginine and Iysine residues Chymotrypsin aromatic amino acids Elastase hydrophobic amino acids  The end products of this surface enzyme activity are free amino acids, and di-and tripeptides which are absorbed across the enterocyte membrane by specific carrier-mediated transport. Di-and tri-peptides are further hydrolyzed to their constituent amino acids within the enterocyte. Final step is the transfer of amino acids out of the enterocyte into portal blood. In humans, most globular proteins from animal sources are almost completely hydrolyzed to amino acids in the GI tract, some fibrous proteins, such as keratin, are only partly digested.  Clinical significant Food Allergy Dipeptides and tripeptides can enter the brusborder of mucosal cells; they are immediately hydrolysed into single amino acids. They are then transported into portal vein. Rarely, larger moleculesmay pass paracellularly (between epithelial cells) and enter blood stream. These are immunogenic,causing antibody reaction, leading to food allergy. The allergy to certain food proteins (milk, fish) is believed to result from absorption of partially digested proteins. Celiac disease (gluten-sensitive enteropath) is a disease of malabsorption resulting from immune-mediated damage to the small intestine in response to ingestion of gluten (or gliadin produced from gluten), a protein found in wheat, barley and rye.  Acute pancreatitis: Premature activation of trypsinogen inside the pancreas itself will result in the autodigestion of pancreatic cells. The result is acute pancreatitis. Abnrmalities in protein digestion: In individuals with a deficiency in pancreatic secretion (for example, due to chronic pancreatitis, cystic fibrosis, or surgical removal of the pancreas), the digestion and absorption of fat and protein are incomplete. Amino acid and small peptide intestinal absorption The absorption of amino acids occurs mainly in the small intestine. It is an energy requiring process. These transport systems are carrier mediated and or ATP sodium dependent symport systems. Most free amino acids are taken into enterocytes via sodium-dependent secondary active transport. free amino acids are released from enterocytes into the portal system by sodiumindependent transporters of the basolateral membrane. Therefore, onlyf ree amino acids are found in the portal vein after a meal containing protein. These amino acids are either metabolized by the liver or released into the general circulation. There are different carriers for amino acids: 1. Neutral amino acids (Alanine, Valine, Leucine,Methionine, Phenylalanine,Tyrosine, Isoleucine) 2. Basic amino acids (Lys, Arg) and Cysteine 3. Acidic amino acids (Asp, Glu) Classification of amino acid