Transcript No Slide Title - people.vcu.edu - Virginia Commonwealth University

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):
THE CARRIER HYPOTHESIS:
PASSIVE, FACUILITATED DIFFUSION
THE SIMPLE UNIPORTER
SYMPORT AND ANTIPORT: COUPLED
TRANSPORT
ACTIVE 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 RELEASED
THE 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 <----- CS
THE 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
VM
V
V = VM*S/(KM +S)
THIS IS A “SATURATION”
CURVE
S
THE DOUBLE RECIPROCAL
PLOT
1/V = (KM/VM)(1/S) + 1/VM
1/V
SLOPE = KM/VM
INTERCEPT = 1/VM
1/S
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 TRANSPORT
Na/K ATPASE
PRIMARY ACTIVE TRANSPORT
Na/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
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
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 NONCOMPETITIVE 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 PATHWAYS
GENETIC 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 MICELLES
DIFFUSE INTO CELL
TRIGLYCERIDES AND PHOSPHOLIPIDS
RESYNTHESISED
COMBINE WITH -LIPOPROTEIN AND
FORM CHOLYMICRONS
ENTER LYMPH AFTER EXOCYTOSIS
ENTER 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 CONTRACTIONS
MASS MOVEMENTS
PROTECTIVE SECRETIONS
FORMATION OF FECES
THE DEFICATION REFLEX
DISTENTION OF RECTUM
STIMULATES
INTERNAL ANAL SPHINCTER
(SMOOTH MUSCLE) RELAXES
EXTERNAL ANAL SPHINCTER
(SKELETAL MUSCLE) UNDER
VOLUNTARY CONTROL