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1、Digestive enzymes,mirka.rovenskalfmotol.cuni.cz,Various organs in digestion and absorption,Pancreas is the major organ that synthesizes the digestive enzymes,Small intestine is a principal site of digestion and absorption,Pancreatic enzymes together with bile are poured into the lumen of the descend
2、ing part of the duodenumDigestion of oligomers of AA and saccharides is accomplished by the enzymes in the luminal plasma membranes of enterocytes; these enzymes usually glycoproteinsHydrolysis of di- and tripeptides occurs in the cytoplasm of enterocytes,and there are 3 compartments where digestion
3、 and absorption occur:,Zymogens,Digestive enzymes are usually synthesized as larger inactive precursors zymogens Otherwise they would digest the tissues that synthesize them:acute pancreatitis: premature activation of digestive enzymes produced by pancreas auto-digestion of pancreas; activated phosp
4、holipase A2 converts lecithin to lysolecithin that can damage cell membranes,Synthesis of zymogens,Proteins destined for secretion are synthesized on polysomes of the RERTheir N-terminus contains a signal sequence release of the protein into ER; then, the signal sequence may be clipped offTransport
5、to the Golgi complexThe proteins are stored in vesicles; after stimulus, granules move to the luminal plasma membrane (PM) and fuse with PM exocytosis,Zymogens are activated by proteolysis,Proenzymes (zymogens) are activated by proteolytic cleavage in the lumen of the GIT:pepsinogen trypsinogenchymo
6、trypsinogenproelastaseprocarboxypeptidasesprophospholipases,Activation of pepsinogen,Pepsinogen is secreted from the stomach cells Pepsinogen is activated by the proteolytic removal of 44 AA from its N-terminus either as an intramolecular reaction or by active pepsin This reaction takes place at pH
7、values below 5,Activation of pancreatic zymogens in the lumen of the small intestine,Strategies“ that prevent premature zymogen activation,At pH2, the peptide (44 AA) clipped of pepsinogen remains bound to pepsin, masking its active site; it is released by a drop of pH below 2 or by further degradat
8、ion by pepsinPancreatic secretory trypsin inhibitor (PSTI), a small polypeptide, blocks any trypsin that is erroneously activated within the pancreas,Regulation of secretion,Through secretagogues that interact with the receptors on the surface of the exocrine cells signal cascade leading to fusion o
9、f granules with PMCholecystokinin: peptide secreted by cells of small int. after stimulation by AA and peptides from gastric proteolysis, by FA, and by acid pHSecretin: peptide secreted by cells of small int.; stimulated by luminal pH 5,DIGESTION OF PROTEINS,By peptidases (proteases):endopeptidases
10、attack internal bonds:pepsintrypsinchymotrypsinelastaseexopeptidases cleave off 1 AA at a time from the:C-terminus carboxypeptidasesN-terminus aminopeptidases,Classes of peptidases,Peptidases hydrolyze the peptide bond,and differ in substrate specificity:,Pepsins,Acid in the stomach serves to kill o
11、ff microorganisms and to denature proteins (denaturation makes proteins more susceptible to proteolysis)Pepsins are acid stable and pH optimum is about 2!Major products of pepsin action: larger peptide fragments and some free AA; this mix = peptone Importance lies mainly in generation of peptides an
12、d AAs that stimulate cholecystokinin release in the duodenum,Pancreatic enzymes,trypsinchymotrypsinelastasecarboxypeptidasesActive at neutral pH depend on neutralization of gastric HCl by pancreatic NaHCO3 The combined action of pancreatic peptidases results in the formation of free AA and small pep
13、tides (2-8 AA),Intestinal peptidases,Luminal surface of intestinal epithelial cells contains endopeptidases, aminopeptidases, and dipeptidases that cleave oligopeptides released by pancreatic peptidasesProducts: AA, di- and tripeptides absorbed by enterocytes Di- and tripeptides are hydrolyzed by in
14、testinal cytoplasmic peptidases AA are absorbed into the portal blood,DIGESTION OF SACCHARIDES,1) Polysaccharides (starch, glycogen) are attacked by -amylase, which is present in saliva and pancreatic juice (more important) -amylase attacks the internal -1,4-glucosidic bonds products: maltose, malto
15、triose, -limit dextrins,2) Hydrolysis of oligosaccharides is carried out by surface enzymes of the intestinal epithelial cells disaccharidases and oligosaccharidasesThese enzymes often exoglycosidases,Saccharide absorption,End products: monosaccharides, mainly D-glucose, D-galactose, D-fructoseThese
16、 are transported by a carrier-mediated process into enterocytes and then into the blood of the portal venous system,Not everything can be digested,Many plant polymers, including celluloses, hemicelluloses, inulin, pectin, are resistant to human digestive enzymes A small percentage of this dietary fibre“ is hydrolyzed and then anaerobically metabolized by the bacteria of the lower intestinal tractThis bacterial fermentation produces H2, CH4, CO2, H2S, acetate, propionate, butyrate, lactate,
