THE DIGESTIVE SYSTEM III

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THE DIGESTIVE SYSTEM III

• D. C. Mikulecky
• Professor of Physiology
• Virginia Commonwealth University

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ABSORPTION OF SUGARS AND AMINO ACIDS

• THE CARRIER HYPOTHESIS
• PASSIVE VS ACTIVE
• GENETIC LINKS

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CARRIERS (MEMBRANE TRANSPORT PROTEINS)

• THE CARRIER HYPOTHESIS PASSIVE, FACUILITATED
  DIFFUSION
• THE SIMPLE UNIPORTER
• SYMPORT AND ANTIPORT COUPLED TRANSPORT
• ACTIVE TRANSPORT PRIMARY AND SECONDARY

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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

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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

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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 ------gtCS C S
lt----- CS THE REACTION EQUILIBRATES WHEN THE
CONCENTRATIONS ARE EQUAL
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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
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MICHAELIS-MENTEN KINETICS
FOR AN ENZYMATIC REACTION E S ?? ES ?? E
P THE REACTION RATE (V - dS/dt) IS GIVEN
BY V VMS/(KM S) THIS IS A
SATURATION CURVE
VM
V
S
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THE DOUBLE RECIPROCAL PLOT
1/V (KM/VM)(1/S) 1/VM
1/V
SLOPE KM/VM
INTERCEPT 1/VM
1/S
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SYMPORT COUPLED TRANSPORT

• TRANSPORTS TWO SUBSTANCES SIMULTANEOUSLY IN THE
  SAME DIRECTION
• THE FLOW OF THE TWO LIGANDS IS COUPLED

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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
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ANTIPORT COUPLED TRANSPORT

• TRANSPORTS TWO SUBSTANCES IN OPPOSITE DIRECTIONS
• THE FLOW OF THE TWO LIGANDS IS COUPLED

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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

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PRIMARY ACTIVE TRANSPORTNa/K ATPASE
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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

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THE MOTOR FOR PRIMARY ACTIVE TRANSPORT

• THE CRUCIAL REACTION IS
• ATP CARRIER COMPLEX ------gt 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

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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

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ANALOGIES WITH ENZYME KINETICS

• THE KINETICS EXHIBIT SATURATION
• KT AND VMAX
• COMPETITIVE AND NON-COMPETITIVE INHIBITION

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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

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AMINO ACID DIGESTION AND ABSORPTION.

• ALSO SODIUM DEPENDENT SECONDARY ACTIVE TRANSPORT
• DEPENDENCE ON MOLECULAR SIZE.
• SPECIFIC PATHWAYS
• GENETIC LINK WITH KIDNEY

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DIGESTION OF FATS

• TRIGLYCERIDES 10 HYDROLYZED IN STOMACH, REST IN
  DUODENUM
• PHOSPHOLIPIDSPANCREATIC PHOSPHOLIPASES
• GLYCEROL AS 2-MONOGLYCERIDES

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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

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WATER SOLUABLE VITAMINS

• SIMPLE DIFFUSION
• ACTIVE TRANSPORT

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FAT SOLUABLE VITAMINS

• ABSORBED ALONG WITH FATS
• VITAMINS A, D, E, K

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OTHER MINERALS

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

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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.

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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.

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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.

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REGULATION OF IRON ABSORPTION

• TRANSPORT TO BLOOD DEPENDENT ON BLOOD LEVELS
• HYPOTHESIS WHEN BLOOD LEVELS ARE HIGH, MORE
  FERRITIN IS FORMED --gt 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.

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IRON ABSORPTION AND ITS REGULATION
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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.

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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.

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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.

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SOURCE DEPENDENCE

• 2-20 FROM PLANTS IS ABSORBED
• 10-35 OF HEME IRON

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THE LARGE INTESTINE

• PRIMARILY A DRYING AND STORAGE ORGAN
• HAUSTRAL CONTRACTIONS
• MASS MOVEMENTS
• PROTECTIVE SECRETIONS
• FORMATION OF FECES

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THE DEFICATION REFLEX

• DISTENTION OF RECTUM STIMULATES
• INTERNAL ANAL SPHINCTER (SMOOTH MUSCLE) RELAXES
• EXTERNAL ANAL SPHINCTER (SKELETAL MUSCLE) UNDER
  VOLUNTARY CONTROL