1 / 37

THE DIGESTIVE SYSTEM III

THE DIGESTIVE SYSTEM III. D. C. Mikulecky Professor of Physiology Virginia Commonwealth University. ABSORPTION OF SUGARS AND AMINO ACIDS. THE CARRIER HYPOTHESIS PASSIVE VS ACTIVE GENETIC LINKS. CARRIERS (MEMBRANE TRANSPORT PROTEINS ):.

dsciortino
Download Presentation

THE DIGESTIVE SYSTEM III

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. THE DIGESTIVE SYSTEM III D. C. Mikulecky Professor of Physiology Virginia Commonwealth University

  2. ABSORPTION OF SUGARS AND AMINO ACIDS • THE CARRIER HYPOTHESIS • PASSIVE VS ACTIVE • GENETIC LINKS

  3. CARRIERS (MEMBRANE TRANSPORT PROTEINS): • THE CARRIER HYPOTHESIS: PASSIVE, FACUILITATED DIFFUSION • THE SIMPLE UNIPORTER • SYMPORT AND ANTIPORT: COUPLED TRANSPORT • ACTIVE TRANSPORT: PRIMARY AND SECONDARY

  4. THE CARRIER HYPOTHESIS: PASSIVE, FACILITATED DIFFUSION • MEMBRANE PROTEINS ASSOCIATE WITH LIGANDS AT THE CELL SURFACE • THE PROTEIN SURROUNDS THE LIGAND WITH HYDROPHOBIC SIDE GROUPS • THE COMPLEX MOVES TO THE OTHER SIDE OF THE MEMBRANE • THE LIGAND IS RELEASED • THE PROTEIN MOVES BACK TO PICK UP ANOTHER LIGAND MOLECULE

  5. THE SIMPLE UNIPORTER • THE CARRIER MOLECULE RESIDES IN THE MEMBRANE • IT HAS ACCESS TO BOTH SIDES • IT IS SELECTIVE • IT CAN ONLY EQUALIZE THE CONCENTRATION

  6. ANALYSIS OF THE THE SIMPLE UNIPORTER THE CARIER BINDS THE LIGAND REVERSIBLY AT EITHER INTERFACE: C + SL CSL C + SR C SR THE DIRECTION OF THE REACTION IS GOVERNED SOLELY BY THE LAW OF MASS ACTION C + S ------>CS C + S <----- CS THE REACTION EQUILIBRATES WHEN THE CONCENTRATIONS ARE EQUAL

  7. ANALYSIS OF THE THE SIMPLE UNIPORTER THE ENTIRE TRANSPORT PROCESS IS ANALOGOUS TO AN ENZYMATIC REACTION: C + SL CS  C + SR E + S  ES  E + P THIS MEANS THAT THE MATHEMATICS OF CARRIER MEDIATED TRANSPORT IS THE SAME AS THAT FOR MICHAELIS-MENTEN KINETICS

  8. MICHAELIS-MENTEN KINETICS FOR AN ENZYMATIC REACTION: E + S  ES  E + P THE REACTION RATE (V = - dS/dt) IS GIVEN BY V = VM*S/(KM +S) THIS IS A “SATURATION” CURVE VM V S

  9. THE DOUBLE RECIPROCAL PLOT 1/V = (KM/VM)(1/S) + 1/VM 1/V SLOPE = KM/VM INTERCEPT = 1/VM 1/S

  10. SYMPORT : COUPLED TRANSPORT • TRANSPORTS TWO SUBSTANCES SIMULTANEOUSLY IN THE SAME DIRECTION • THE FLOW OF THE TWO LIGANDS IS COUPLED

  11. COUPLED TRANSPORT CAN BE DESCRIBED BY NON-EQUILIBRIUM THERMODYNAMICS • THERMODYNAMICS OF THE STEADY STATE PHENOMENOLOGICAL EQUATIONS: J1 = L11 X1 + L12 X2 J2 = L21 X1 + L22 X2 DISSIPATION FUNCTION: T dS/dt= J1 X1 + J2 X2

  12. ANTIPORT: COUPLED TRANSPORT • TRANSPORTS TWO SUBSTANCES IN OPPOSITE DIRECTIONS • THE FLOW OF THE TWO LIGANDS IS COUPLED

  13. ACTIVE TRANSPORT: PRIMARY AND SECONDARY • PRIMARY ACTIVE TRANSPORT INVOLVES THE DIRECT COUPLING OF METABOLIC ENERGY (ATP) TO MASS TRANSPORT • SECONDARY ACTIVE TRANSPORT INVOLVES THE PUMPING OF ON CHEMICAL SPECIES AGAIST AN ELECTROCHEMICAL GRADIENT AT THE EXPENSE OF A SECOND

  14. PRIMARY ACTIVE TRANSPORTNa/K ATPASE

  15. PRIMARY ACTIVE TRANSPORTNa/K ATPASE • 1- SODIUM IS COMPLEXED • 2- CARRIER PHOSPHORYLATED • 3- CARRIER MOVES TO OTHER SIDE RELEASING SODIUM • 4- CARRIER BINDS POTASSIUM AND PHOSPHTE IS REMOVED • 5- CARRIER MOVES TO OTHER SIDE • 6- CARRIER RELEASES POTASSIUM • 7- CARRIER RETURNS TO STEP 1

  16. THE “MOTOR” FOR PRIMARY ACTIVE TRANSPORT • THE CRUCIAL REACTION IS: • ATP + CARRIER COMPLEX ------> ADP + CARRIER COMPLEX-P • THIS REACTION CAN BE DRIVEN TO A HIGH CONCENTRATION OF COMPLEX IF SUFFICIENT ATP IS PRESENT • THIS IS THE “MOTOR” WHICH DRIVES THE CYCLE AND ALLOWS UPHILL TRANSPORT

  17. SECONDARY ACTIVE TRANSPORT • WHEN TRANSPORT OF TWO SUBSTANCES IS COUPLED, THE GRADIENT OF ONE CAN SUPPLY THE ENERGY FOR MOVING THE OTHER UPHILL • SYMPORTS AND ANTIPORTS CAN DO THIS • AN EXAMPLE IS SUGAR TRANSPORT IN THE GUT: DRIVEN BY THE SODIUM GRADIENT ACROSS THE APICAL CELL MEMBRANE

  18. ANALOGIES WITH ENZYME KINETICS • THE KINETICS EXHIBIT SATURATION • KT AND VMAX • COMPETITIVE AND NON-COMPETITIVE INHIBITION

  19. SODIUM DEPENDENCE THE SUGAR/NA+ SYMPORT • CARRIER BINDS SUGAR AND SODIUM AS A SYMPORT • SECONDARY ACTIVE TRANSPORT • CARRIER COMPLEX USES ENERGY STORED IN SODIUM GRADIENT

  20. AMINO ACID DIGESTION AND ABSORPTION. • ALSO SODIUM DEPENDENT SECONDARY ACTIVE TRANSPORT • DEPENDENCE ON MOLECULAR SIZE. • SPECIFIC PATHWAYS • GENETIC LINK WITH KIDNEY

  21. DIGESTION OF FATS • TRIGLYCERIDES: 10% HYDROLYZED IN STOMACH, REST IN DUODENUM • PHOSPHOLIPIDS:PANCREATIC PHOSPHOLIPASES • GLYCEROL: AS 2-MONOGLYCERIDES

  22. ABSORPTION OF FATS • SOLUABALIZED IN MICELLES • DIFFUSE INTO CELL • TRIGLYCERIDES AND PHOSPHOLIPIDS RESYNTHESISED • COMBINE WITH -LIPOPROTEIN AND FORM CHOLYMICRONS • ENTER LYMPH AFTER EXOCYTOSIS • ENTER BLOOD VIA THORACIC DUCT

  23. WATER SOLUABLE VITAMINS • SIMPLE DIFFUSION • ACTIVE TRANSPORT

  24. FAT SOLUABLE VITAMINS • ABSORBED ALONG WITH FATS • VITAMINS A, D, E, K

  25. OTHER MINERALS: • LARGE SURFACE AREA MAKES PASSIVE DIFFUSION ADEQUATE FOR THE ABSORPTION OF MANY SUBSTANCES. SPECIAL MECHANISMS EXIST FOR MANY, IN SPITE OF THIS.

  26. SOLUBILITY AND THE INTERACTION BETWEEN NUTRIENTS: • MANY SUBSTANCES, SUCH AS OXALATE, PHYTIC ACID, AND PHOSPHATE FORM INSOLUBLE PRECIPITATES WITH OTHER NUTRIENTS. • MOST NUTRIENTS MUST BE SOLUBLE FOR ABSORPTION. CALCIUM, MAGNESIUM, ZINC, IRON, ALUMINUM, AND BERYLLIUM ARE AMONG THESE. • ALSO MOST OF THEIR SALTS ARE LESS SOLUBLE IN ALKALINE SOLUTIONS. • FIBER HAS BEEN IMPLICATED IN REDUCING THE ABSORPTION OF MINERALS AS WELL.

  27. OTHER MINERALS • POTASSIUM: ABSORBED PASSIVELY ALONG ENTIRE SMALL INTESTINE. IF LUMINAL LEVELS BECOME LOWER THAN SERUM (4 - 5 MEQ/L), NET SECRETION WILL OCCUR IN ILEUM AND COLON. • MAGNESIUM: AVERAGE DAILY DIET CONTAINS 10MILLIMOLES OF WHICH LESS THAN HALF IS ABSORBED. PASSIVELY ABSORBED ALONG THE ENTIRE SMALL INTESTINE. • PHOSPHATE: ABSORPTION ALL ALONG SMALL INTESTINE BY PASSIVE AND ACTIVE TRANSPORT.

  28. COPPER AND CALCIUM • COPPER: ABSORBED IN THE JEJUNUM. ABOUT 50% OF THE INGESTED LOAD ABSORBED. SOME COPPER IS SECRETED IN THE BILE IN A BOUND FORM AND THIS IS LOST IN THE FECES. FAILURE OF THIS SECRETION MECHANISM RESULTS IN ACCUMULATION IN CERTAIN TISSUES. • CALCIUM:ACTIVELY ABSORBED. VITAMIN D INVOLVED.

  29. REGULATION OF IRON ABSORPTION • TRANSPORT TO BLOOD DEPENDENT ON BLOOD LEVELS • HYPOTHESIS: WHEN BLOOD LEVELS ARE HIGH, MORE FERRITIN IS FORMED --> MORE "TRAPPED" IN CELLS. IN IRON DEFICIENCY, MORE TRANSPORT PROTEIN IS SYNTHESIZED AND LESS FERRITIN. • IRON TRAPPED IN CELL BOUND TO FERRITIN IS LOST WHEN CELLS SLOUGH OFF AND DISINTEGRATE, SINCE IT CAN NOT GET INTO THE INTACT CELLS IN THIS FORM.

  30. IRON ABSORPTION AND ITS REGULATION

  31. STEPS IN IRON ABSORPTION • 1) IRON IN HEME IS ABSORBED DIRECTLY AND THEN THE IRON IS RELEASED FROM THE HEME INSIDE THE CELL AND IS COMBINED WITH NONHEME IRON. • 2) NONHEME IRON BOUND TO COMPONENTS OF FOOD MUST BE LIBERATED ENZYMATICALLY. MANY FACTORS INFLUENCE THE BIOAVAILABILITY OF IRON.

  32. STEPS IN IRON ABSORPTION • 3)IRON IS ABSORBED BEST IN THE FERROUS FE2+ FORM. THIS IS MAINLY DUE TO HIGHER SOLUBILITY. • 4) IRON CROSSES THE CELL MEMBRANE • 5) ONCE INSIDE, BINDING TO APOTRANSFERRIN SEEMS TO FACILITATE ITS ENTRY.

  33. STEPS IN IRON ABSORPTION • 6) DEPENDING ON THE LEVEL OF IRON STORES AND BLOOD LEVELS OF IRON, THE IRON CAN BE STORED INSIDE THE EPITHELIAL CELL OR MOVED TO THE BLOOD • 7) THE IRON IS TRANSPORTED OUT OF THE CELL INTO THE PLASMA. ONCE IN THE PLASMA, THE IRON IS OXIDIZED TO THE FERRIC FORM BY CERULOPLASMIN AND IS THEN TAKEN UP BY TRANSFERRIN.

  34. SOURCE DEPENDENCE: • 2-20% FROM PLANTS IS ABSORBED • 10-35% OF HEME IRON

  35. THE LARGE INTESTINE • PRIMARILY A DRYING AND STORAGE ORGAN • HAUSTRAL CONTRACTIONS • MASS MOVEMENTS • PROTECTIVE SECRETIONS • FORMATION OF FECES

  36. THE DEFICATION REFLEX • DISTENTION OF RECTUM STIMULATES • INTERNAL ANAL SPHINCTER (SMOOTH MUSCLE) RELAXES • EXTERNAL ANAL SPHINCTER (SKELETAL MUSCLE) UNDER VOLUNTARY CONTROL

More Related