Protein Metabolism PDF

DIGESTION OF PROTEINS  Dietary proteins Proteins which we take in our diet are either from animal source or vegetable source. Principal animal sources: Milk and dairy products, meat, fish, liver, eggs Principal vegetable sources:...

DIGESTION OF PROTEINS  Dietary proteins Proteins which we take in our diet are either from animal source or vegetable source. Principal animal sources: Milk and dairy products, meat, fish, liver, eggs Principal vegetable sources: Cereals, pulses, peas, beans and nuts The intake of dietary protein is in the range of 50-100 g/day g/day of endogenous protein is derived form the About 30-100 digestive enzymes and worn out cells of the digestive tract. Very little protein (about 5-10 g/day) is lost through feces  DIGESTION IN MOUTH There are no proteolytic enzymesAfter in mouth: mastication and chewing, the bolus of food reaches stomach where it meets the gastric juice. Proteolytic enzymes responsible for the digestion of proteins are produced by the stomach, the pancreas and the small intestine. Proteins are not digested in the mouth due to the absence of proteases in saliva. Proteins are degraded by a class of enzymes Namely hydrolases: Which specifically cleave the peptide bonds, hence known as peptidases. Endopeptid Exopeptid They are divided into two groups ases ases (proteases) Which act on the peptide bonds of terminal amino acids Which attack the internal peptide bonds and carboxypeptid aminopeptid release peptide ases ases fragments, e.g. pepsin, trypsin. (act on C-terminal (act on N-terminal amino acid) amino acid) DIGESTION IN STOMACH Gastric juice: Contains a number of proteolytic enzymes HCL Pepsi n Renni n Gastris cin Gelatin ase  Hydrochloric acid HCL: The pH of the stomach is < 2 due to the presence of HCl, secreted by parietal (oxyntic) cells of gastric gland. This acid performs two important functions- denaturation of proteins and killing of certain microorganisms. The denatured proteins are more susceptible to proteases for digestion.  Pepsin Potent proteolytic enzyme and is present in gastric juices synthesised in “chief cells” of stomach. It is secreted as inactive zymogen form, pepsinogen, (mol. wt.; 42,500 approx. 99% is poured in gastric juice as pepsinogen and 1% secreted in the blood stream and ultimately excreted in the urine as urinary pepsin (uropepsin). MWt:34,500 MWt:42,500 act as stimulants for the release of the hormone cholecystokinin  Pepsin is an acid-stable endopeptidase optimally active at a very low pH (2.0). Optimum pH for pepsin is 1.6 to 2.5 and pepsin gets denatured if the pH is greater than 5. Pepsin is a proteinase, a non-specific endopeptidase, and it hydrolyses peptide bonds well inside the protein molecule and produces proteoses and peptones. It is particularly active on a peptide bond, which connects the –COOH group of an aromatic amino acid like Phe, Tyr, and Tryp with the amino group.  Rennin Also called chymosin. Found in the stomach of infants and children. Absent in adults. Rennin is involved in the curdling of milk. It converts milk protein casein to calcium paracaseinate which can be effectively digested by pepsin.  Gastriscin The enzyme is secreted in the gastric juice of humans as inactive zymogen form, Which is activated in presence of HCl. Optimum pH is 3 to 4. It acts as a Proteinase and requires an acidic medium for its activity. Gelatinase Gelatin is hydrolysed by the enzyme Gelatinase present in gastric juice. It acts in an acidic medium.  DIGESTION IN DUODENUM Food after leaving stomach reaches duodenum, where it meets with pancreatic juice. Proteolytic enzymes are present in Pancreatic juice to act on proteins and partly digested products. Proteases of pancreatic juice are secreted as zymogens (proenzymes) and then converted to active forms. Cholecystokinin and secretin from the intestine stimulate to secrete the Pancreatic juice. Trypsin Chymotrypsin Chief Carboxy enzymes are peptidases Elastases Collagenases.  Trypsin Trypsin, a proteinase, is secreted as an inactive zymogen form trypsinogen. hexapeptide (6 pH of 5.5 aa fragment) from the N- terminal end of trypsinogen to produce active trypsin. Trypsin acts in an alkaline medium pH 8 to 9 (optimum pH-7.9) A glycoprotein Enteropeptidase (enterokinase) produced by intestinal (mostly duodenal) mucosal epithelial cells. Trypsin is the common activator of all other pancreatic zymogens to produce the active proteases, namely chymotrypsin, elastase and Chymotrypsin Chymotrypsin, a proteinase is secreted as inactive zymogen chymotrypsinogen. α-Chymotrypsin is the active form, it is included under serine proteases like trypsin. Optimum pH = 7 to 8.  Carboxy Peptidases Carboxy peptidas es Carboxy Carboxy peptidase peptidase A B  Carboxy peptidase A It is a metalloenzyme, contains zinc (Zn-protein). Secreted as inactive zymogen procarboxy peptidase A. Trypsin converts subunit II to a proteinase and subunit III is degraded. changes subunit I of procarboxy peptidase A to active carboxy peptidase A. The enzyme hydrolyses the terminal peptide bond connected to an end a.a bearing free α- COOH group, particularly if the end a.a is Tyr, Phe or Trypt. It liberates the end a.a as “free” form, so that the peptide becomes shorter by one a.a.  Carboxy Peptidase B It is also an “exopeptidase”. Also hydrolyses terminal peptide bonds, which are connected with “basic” amino acids e.g., Arg, Lysine bearing free-COOH gr. Similarities of both carboxy peptidases A and B Both are exopeptidases: Optimum pH = 7.5 for both. Both enzymes are ineffective in hydrolysing dipeptides.  Elastase and Collagenase Elastase: A serine protease, secreted as inactive zymogen proelastase, activated by trypsin to active elastase. The enzyme has maximum activity on peptide bonds connected to carbonyl groups of neutral aliphaticAn Collagenase: a.a. enzyme which can act on proteins present in collagen. Both the enzymes can digest yellow and white connective tissue fibres respectively to yield peptides. (Cholecystokinin)  DIGESTION IN SMALL INTESTINE Proteolytic enzymes present in intestinal juice: Amino Enterokinase peptidases Tri and Di- Prolidase peptidases  Enterokinase Also known as enteropeptidase. A glycoprotein enzyme, also present in the epithelial cells of brushborder of duodenal mucosa and secreted in duodenum. Action: It hydrolyses a peptide bond connected to a lysine residue in pancreatic trypsinogen, so that an inactive hexapeptide is split off from the N- terminal end and “active” trypsin is produced.  Amino Peptidases Can hydrolyse peptides to tripeptides but cant hydrolyse a dipeptide. Requires presence of Zn++, Mn++ and Mg++ which help in formation of a metal-enz-substrate coordination complex for the catalysis. Can hydrolyse a terminal peptide bond connected to an end a.a bearing a free-α NH2 group and thus splits off the end a.a. from the N-terminal end of a peptide, changing the latter gradually stepwise to a “tripeptide”. Cannot hydrolyse a peptide bond connected with a proline residue.  Prolidase An exopeptidase and can hydrolyse a proline peptide of collagen molecule, acts on terminal peptide bond connected to proline as end a.a, liberating a proline molecule. Tri and Di-peptidases Tri-peptidase acts on a tri-peptide and produces a di- peptide and free a.a. A di-peptidase hydrolyses a di-peptide to produce two molecules of amino acids. They require the presence of Mn++, Co++ or Zn++ as cofactors for their activity. Enzymes hydrolyse the peptides in microvillus membrane of intestinal epithelial cells, or inside the epithelial cells after the peptides have been absorbed inside the cell. Digestion of proteins—Specificity of enzyme cleavage of peptide bonds. ( R1 can be from any amino acid)  Action of proteolytic enzyme Action of proteases  ABSORPTION OF AMINO ACIDS Under normal circumstances, the dietary proteins are almost completely digested to their constituent amino acids. But some amounts of oligopeptides like tri and dipeptides may remain as such.  Site of Absorption Amino acids are absorbed from ileum and distal jejunum. Oligopeptides like di and tri-peptides are absorbed from duodenum and proximal jejunum.  How Do They Reach Liver? Amino acids and other products of digestion like di and tripeptides, if any, after absorption are carried by portal blood to Liver. The portal vein (PV) is the main vessel of the portal venous system (PVS), which drains the blood from the gastrointestinal tract, gallbladder, pancreas, and spleen to the liver. Rate of Absorption There is difference in rate of absorption from the intestine of the two isomers. L-amino acids and L-peptides are absorbed more rapidly than D-isomers and they have been shown to be absorbed by‘active’ transport process. D-amino acids are absorbed slowly and they are Chief cells Chief cells Activation High pH, Inactive pepsi Pancrease Overview of digestion of proteins Thank you