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PROTEIN METABOLISM DEPT OF BIOCHEMISTRY ACS MEDICAL COLLEGE CHENNAI - 77 DIGESTION & ABSORPTION DIETARY PROTEINS SERVE 3 FUNCTIONS 1. THEIR CONSTITUTENT AMINOACIDS ARE USED FOR SYNTHESIS OF BODY PROTEINS 2. THE CARBON SKELETONS OF THE AMINO ACIDS ARE OXIDISED TO YIELD ENERGY 3. THEIR CARBON & NITROGEN ATOMS MAY BE USED TO SYNTHESISE OTHER ‘N’ CONTAINING CELLULAR CONSTITUENTS AS WELL AS MANY NONNITROGEN CONTAINING METABOLITES DIGESTION TAKES PLACE WITH THE HELP OF ENZYMES SECRETED BY 1. STOMACH 2. PANCREAS 3. SMALL INTESTINE 1.DIGESTION IN STOMACH ENTERING PROTEINS (+) GASTRIN (+) GASTRIC JUICE (pH 1.5 – 2.5) CONTAINING 1. HCL 2. PEPSINOGEN 3. RENNIN (IN INFANTS) HYDROCHLORIC ACID • SECRETED BY PARIETAL CELLS • KILLS MICRO-ORGANISMS • DENATURES PROTEIN MAKING INTERNAL PEPTIDE BONDS MORE SUSCEPTIBLE TO SUBSSEQUENT HYDROLYSIS BY PROTEOSES • PROVIDES ACID ENVIRONMENT FOR PEPSIN ACTION PEPSIN • SECRETED BY CHIEF CELLS AS PEPSINOGEN – INACTIVE PRECURSOR • CONVERTED TO ACTIVE PEPSIN BY AUTOCATALYSIS • WORKS AT ACIDIC pH • CLEAVES PEPTIDE BONDS INVOLVING AROMATIC & ACIDIC AA PEPSINOGEN PEPSIN H+(pH 1.5 – 2.5) PEPSIN DIETARY PROTEIN SMALLER PEPTIDES + AA RENNIN • CHYMOSIN / RENNET • IMPORTANT IN INFANTS DIGESTIVE PROCESS • CLOTTING OF MILK CASEIN R PARACASEIN Ca++ Ca++PARACASEINATE THE PURPOSE OF THIS REACTION IS TO CONVERT MILK INTO MORE SOLID FORM TO PREVENT THE RAPID PASSAGE OF MILK FROM STOMACH OF INFANTS 2.DIGESTION IN INTESTINE BY PANCREATIC ENZYMES ACIDIC CONTENTS (CHYME) PASSING INTO SMALL INTESTINE TRIGGERS THE SECRETION OF 1. SECRETIN 2. CHOLECYSTOKININ SECRETIN • STIMULATES PANCREAS TO SECRETE BICARBONATE & RELEASE OF PANCREATIC JUICE INTO THE SMALL INTESTINE. • NEUTRALISES GASTRIC HCL CHANGING pH FROM 1.5 – 7.0 CHOLECYSTOKININ • STIMULATES SECRETION OF PANCREATIC ENDOPEPTIDASE & EXOPEPTIDASE • ENDOPEPTIDASE INCLUDES CHYMOTRYPSIN & ELASTASE, CLEAVING INTERNAL PEPTIDE BONDS • EXOPEPTIDASE CLEAVES 1 AA AT A TIME FROM EITHER ‘C’ OR ‘N’ END. INCLUDES CARBOXYPEPTIDASE & AMINOPEPTIDASE ACTIVATION OF PANCREATIC PRO-ENZYMES TRYPSINOGEN ENTEROPEPTIDASE TRYPSIN CHYMOTRYPSINOGEN PRO-ELASTASE PROCARBOXYPEPTIDASE CHYMOTRYPSIN ELASTASE CARBOXYPEPTIDASE • TRYPSIN – HYDROLYSES PEPTIDE BONDS WHOSE CRBOXYL GROUPS ARE CONTRIBUTED NY LYS & ARG RESIDUES • CHYMOTRYPSIN-CLEAVES PEPTIDE BONDS INVOLING CARBOXYL GROUP OF AROMATIC AA • ELASTASE – HYDROLYSES THOSE PEPTIDE BONDS FORMED BY SMALL NONPOLAR AA RESIDUES SUCH AS ALA, SER & GLY • THUS 3 ENZYMES HYDROLYSE POLYPEPTIDES TO SMALLER PEPTIDES Degradation of short peptides in the small intestine is continued by an EXOPEPETIDASE- CARBOXYPEPTIDASE which removes the successive carboxy terminal aa residues from peptide 1. CARBOXYPEPTIDASE ‘A’ – RELEASES HYDROPHOBIC AA 2. CARBOXYPEPTIDASE ‘B’ – RELEASES BASIC AA 3.DIGESTION IN INTESTINE BY INTESTINAL PROTEOSES • The digestion is completed by the PEPTIDASES of the mucosa of the small intestine namely: 1. AMINOPEPTIDASES 2. GROUP OF DIPEPTIDASES AMINO-PEPTIDASE - EXOPEPTIDASE - REQUIRE Mg/Mn - HYDROLYSE PEPTIDE BONDS NEXT TO N-TERMINAL AA OF SHORT PEPTIDES DIPEPTIDASES - COMPLETE THE DIGESTION OF DIPEPTIDES TO FREE AMINO ACIDS ABSORPTION OF AMINOACIDS • MOSTLY THRU ACTIVE TRANSPORT • 5 SEPARATE SYSTEMS – TRANSPORT LAMINOACIDS FROM INTESTINAL LUMEN INTO INTESTINAL EPITHELIAL CELLS • THUS AA RELEASED BY DIGESTION PASS FRM GUT THRU HEPATIC PORTAL VEIN TO THE LIVER • TRANSPORT SYSTEM ALSO PRESENT IN RENAL SYSTEM TRANSPORT SYSTEM AMINOACID TRANSPORTD DISORDER Small neutral aminoacids Ala Ser & Thr Large neutral aminoacids Basic aa & Cysteine Isoleu, Leu, Val,Tyr,Trp,Ph e Arg, Lys, CYSTINUTIA Ornithine, Cys Acidic aminoacids Glutamic acid Aspartic acid Iminoacid, Glycine Pro, Hydroxy pro, Gly HARTNUP Disease GLYCINURIA MEISTER CYCLE GAMMA GLUTAMYL CYCLE AMINO ACID GLUTATHIONE GLUTAMYL AMINOACID CYSTEINYL GLYCINE AMINOACID GLYCINE CYSTEINE OXOPROLINE GLUTAMYL-CYSTEINE GLUTAMATE