THE DIGESTIVE SYSTEM III

D. C. MikuleckyProfessor of PhysiologyVirginia Commonwealth University

ABSORPTION OF SUGARS AND AMINO ACIDS

THE CARRIER HYPOTHESISPASSIVE VS ACTIVEGENETIC LINKS

CARRIERS (MEMBRANE TRANSPORT

PROTEINS):

THE CARRIER HYPOTHESIS: PASSIVE, FACUILITATED DIFFUSION

THE SIMPLE UNIPORTERSYMPORT AND ANTIPORT:

COUPLED TRANSPORTACTIVE TRANSPORT: PRIMARY

AND SECONDARY

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 RELEASEDTHE PROTEIN MOVES BACK TO PICK UP

ANOTHER LIGAND MOLECULE

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

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 <----- CSTHE REACTION EQUILIBRATES WHEN THE CONCENTRATIONS ARE EQUAL

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

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

V

S

VM

THE DOUBLE RECIPROCAL PLOT

1/V

1/S

SLOPE = KM/VM

INTERCEPT = 1/VM

1/V = (KM/VM)(1/S) + 1/VM

SYMPORT : COUPLED TRANSPORT

TRANSPORTS TWO SUBSTANCES SIMULTANEOUSLY IN THE SAME DIRECTION

THE FLOW OF THE TWO LIGANDS IS COUPLED

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

ANTIPORT: COUPLED TRANSPORT

TRANSPORTS TWO SUBSTANCES IN OPPOSITE DIRECTIONS

THE FLOW OF THE TWO LIGANDS IS COUPLED

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

PRIMARY ACTIVE TRANSPORTNa/K ATPASE

PRIMARY ACTIVE TRANSPORTNa/K ATPASE

1- SODIUM IS COMPLEXED2- CARRIER PHOSPHORYLATED3- CARRIER MOVES TO OTHER SIDE

RELEASING SODIUM4- CARRIER BINDS POTASSIUM AND

PHOSPHTE IS REMOVED5- CARRIER MOVES TO OTHER SIDE 6- CARRIER RELEASES POTASSIUM7- CARRIER RETURNS TO STEP 1

THE “MOTOR” FOR PRIMARY ACTIVE TRANSPORT

THE CRUCIAL REACTION IS:ATP + CARRIER COMPLEX ------> ADP +

CARRIER COMPLEX-PTHIS 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

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

ANALOGIES WITH ENZYME KINETICS

THE KINETICS EXHIBIT SATURATION

KT AND VMAX

COMPETITIVE AND NON-COMPETITIVE INHIBITION

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

AMINO ACID DIGESTION AND ABSORPTION.

ALSO SODIUM DEPENDENT SECONDARY ACTIVE TRANSPORT

DEPENDENCE ON MOLECULAR SIZE.

SPECIFIC PATHWAYSGENETIC LINK WITH KIDNEY

DIGESTION OF FATS

TRIGLYCERIDES: 10% HYDROLYZED IN STOMACH, REST IN DUODENUM

PHOSPHOLIPIDS:PANCREATIC PHOSPHOLIPASES

GLYCEROL: AS 2-MONOGLYCERIDES

ABSORPTION OF FATS

SOLUABALIZED IN MICELLESDIFFUSE INTO CELLTRIGLYCERIDES AND PHOSPHOLIPIDS

RESYNTHESISEDCOMBINE WITH -LIPOPROTEIN AND

FORM CHOLYMICRONSENTER LYMPH AFTER EXOCYTOSISENTER BLOOD VIA THORACIC DUCT

WATER SOLUABLE VITAMINS

SIMPLE DIFFUSION

ACTIVE TRANSPORT

FAT SOLUABLE VITAMINS

ABSORBED ALONG WITH FATS

VITAMINS A, D, E, K

OTHER MINERALS:

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

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.

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.

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.

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.

IRON ABSORPTION AND ITS REGULATION

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.

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.

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.

SOURCE DEPENDENCE:

2-20% FROM PLANTS IS ABSORBED

10-35% OF HEME IRON

THE LARGE INTESTINE

PRIMARILY A DRYING AND STORAGE ORGAN

HAUSTRAL CONTRACTIONSMASS MOVEMENTSPROTECTIVE SECRETIONSFORMATION OF FECES

THE DEFICATION REFLEX

DISTENTION OF RECTUM STIMULATES

INTERNAL ANAL SPHINCTER (SMOOTH MUSCLE) RELAXES

EXTERNAL ANAL SPHINCTER (SKELETAL MUSCLE) UNDER VOLUNTARY CONTROL