Protein and carbohydrate digestion and absorption

From Iusmphysiology

• started here on 02/21/11 at 11AM.

Contents 1 Protein and carbohydrate digestion and absorption 1.1 Objectives 1.2 The exocrine pancreas 1.2.1 Acinar cells and zymogens 1.2.1.1 Cellular pathways 1.2.1.2 Duct cells secrete isotonic NaHCO3 1.2.2 Regulation of secretion 1.2.3 Hormones 1.2.4 Pancreatitis 1.2.5 Cystic fibrosis 1.3 Digestion 1.4 Carbs 1.4.1 Absorption 1.4.2 Clinical applications 1.5 Protien digestion 1.5.1 Proteases are secretead as inactive precursors 1.5.2 Oligopeptide absorption 1.5.3 Defects in apical aa transporters 1.5.4 Absorption of water soluble vitamins 1.5.5 Dietary folate absorption 1.5.6 GAstric intrinsic factor and intestinal vitamin b12 absorption 1.6 Summary

[edit] Protein and carbohydrate digestion and absorption

We're talking aobut how the intestine digests foods.

[edit] Objectives

• Pancreas is an important secondary organ for digestion.
  • We'll tlak about secretions and regulation.

[edit] The exocrine pancreas

• Just under the stomach.
• Connects to duodenum thorugh pancreatic duct
  • Joins the bile duct just before.
• Secretes digestive enzymes
• Also neutralizes lumenal contents
  • Chyme from stomach is very acidic
  • Must neutralize the acids to allow enzymes to work.
• Salivary glands and the exocrine glands are similar = compound exocrine glands.
• There are acinar surrounding the ducts
• Acinar cells make the protein secretions, put them into the ducts, which take them to the duodenum.
  • Acinar cells are epithelial cells
• Prteoins go through golgi and rough ER
• Protein sput in zymogen granules
  • Zymogens are inctive enzymes
  • Activated upon enterance into the lumen.
• Ducts are lined with these pancreatic ductal epithelial cells
  • Specialized for fluid and electrolyte export
  • Help neutralize acids
• Ducts also have goblet cells
  • MUcus helps with movmeent and protection

[edit] Acinar cells and zymogens

• Acinar cells release enzymes
• Stimulated by CCK and muscarinic receptors (ach).
  • Use Ca as second messenger
• VIP and Secretin also stimulate
  • Use cAMP as second messsneger

Two other cell types

[edit] Cellular pathways

• Don't need to know all the details
• PKC and PLC are important.
• An actin network restricts the movement of the vesciles to the membrane.
• Fusion increases the apical plasma membrane surface area 30-fold.
• Acinar cells secrete a NaCl rich fluid which pulls water and hleps to hydrate the secretion.
• One of the key transport proteins is the beta-lactate, ATP dependent Na transporter.
  • Puts Na on the outside
  • Provides secondary electrochemical gradient energy for other transporters.
• Cl is taken from the interstitial space on the basal membrane, into the cell, and then into the lumen.
  • Water follows.
• CCK increases intracellular Ca to increase Kinases to increase Ca channels for uptake and secretion into the lumen.

[edit] Duct cells secrete isotonic NaHCO3

• Bicarb is moved with Na to help neutralize acid of the stomach.
• Bicarb excreted through bicarb-Cl antiporter.
• Bicarb can come from blood or from Carbonic Anhydrase (CA).
  • Protoons are left over when CA used.
  • So we use proton pumps to put hydrogens into the blood to keep intracellular pH low.
• Transproter of naHco3 is drivin by Cl gradient
  • CFTR is activated by cAMP (think ach and secretin).
  • CFTR is the rate limiting step
  • Secretes cl so NaHCO3 can follow
  • In CF, CFTR doesn't work so not enough bicarb is secreted to neutralize acid from stomach.

[edit] Regulation of secretion

• Three phases of regulation (like with stomach secretion regulation).
• Cephalic:
  • Recepotrs in the head
  • Sight or smell, activation occurs.
  • HOrmones or neurons work on acinar cells via ach
  • Gastrin can bind to acinar cells ti sstimulate release, too.
  • Ach on ductal cells can stimulate HCO3 release.
• GAstric phase:
  • Stimuli within the stomach
  • GAstric distension: vagal-vagal
  • Rlease of gastrin which regulates secretion
  • Similar pathways as with cephalic but initiated by signals in the stomach, through the brain, then on the pancrease (acinar, ductal, etc.)
• Intestinal phase
  • Acid on the S cells within the duodenum stimulates secretion of secretin
    • Goes through paracrine and endocrine to stimulate ductal cells to secrete bicarb.
  • Pancreatic secretion inhibited when lipids get to the distal samll intestine
  • Stimuli comes from the intestine itself.
  • Acid on I cells cause release of CCK.
    • CCK goes through endocrine to cause rlease of...

[edit] Hormones

• SEcretin is a 27 aa hormone
  • Produced by S cells in duodenum
  • Release is stimulated by acidic pH
  • Stimulates:
• CCK

Look at this slide.

[edit] Pancreatitis

• Acute:
  • Gallstones can cause this because it can block the bile duct and pancreatic duct.
  • Acinar cells borked
  • Injury will be perpetuated by infammatory response
• Chronic:
  • Happens when tissue starts to scare
  • Can happen in alcohole abuse
  • Occurs in cystic fibrosis
  • Abdomenal pain
  • Steatorrhea
  • Malnutrition can both occur because of and cause CF.
• Treatment:
  • Give protease inhibitors to stop the enzymes from damagine body
  • Give enzyme supplements to avoid malnutrition
  • Surgery to remove the blockage or increase drainage.

[edit] Cystic fibrosis

• Mutations in CFTR causing it to be degraded.
• Should be on the apical membrane of the ductal cells to help hydrate and neutralize.
• Thickening of secretion causes obstruction.
• Scarring occurs.
• Enzyme deficiency occurs.
  • Steatorrhea occurs
• Must give supplemental enzymes for proper digestion

[edit] Digestion

• Usually a two step process: bulk lumenal phase, then smaller phase.
• Smaller particles digested by brush border enzymes.
• Very small particles absorbed by epithelial cells.

[edit] Carbs

• Many types
• Non digestible
  • Pass through
• Starch
  • Amylase breaks it down into maltose, and alpha-lima dextrose (small disaccharides)
  • Disaccharideases break them down into monosacchs
  • Monosacchs absorbed
  • Disaccharides:
    • Lactase: lactose to glucose and galactose (which are absorbed by SGLT1, a Na transporter)
    • Glucoamylase: maltose and maltitriose to glucose (which is absorbed through SGLT1)
    • Sucrase / isomaltase (alpha dextrinase): Sucrose to glucose and fructose, and side chains to glucose (glucose through SGLT1, fructuse through facilitation of GLUT5)

[edit] Absorption

• Na gradient needed for Na-coupled transport
  • Recall that beta-lact? sets up the Na gradient.
• Fructose is moved by faciliated diffusion so it doesn't require the Na gradient.

[edit] Clinical applications

• Malaborption of carbohydrates.
• Lactose intolerance:
  • If you don't have lactase
  • CAuses diarrhea, cramps, and gas
  • Lactose stays int he lumen acts as a osmolyte.
  • Colonic bacteria uses the lactose and gives of CO2 and H2
    • Can even detect with high H2 expiration
• Villous attrophy
  • Low surface area = poor absorption
• Fruit=juic diarrhea
  • Can't absorb fast enough,
  • Get an osmotic load in the intestine, causes diarrhea
• Oral rehydration solution
  • Cheap, effective
  • Treatment for diarrhea
  • Especially good for exotoxins and bacteria

[edit] Protien digestion

• Pancreas make sproteases
  • Pepsin, trypsin, chymotripsin, elastase, carobxypeptidases
• Absorb aa, or even short peptides.
• Peptidases on the membrane can take peptides and break them down into smaller peptides.
• There are di and tri-peptide transporters, too.
  • Borken down into aa
  • Then put in blood

Energy source?

• Aa tranporters are moved with Na-AA cotransporter
  • Again, drivn by Na gradient
• These proteins will not just be that which we eat but also the proteins from our shedd epithelial cells.

[edit] Proteases are secretead as inactive precursors

• Pepsinogen, for example, gets activated by low pH into pepsin.
• Enterokinase in the lumen of the intestine activates trypsinogen into tyrpsin.
  • Trypsin can auto activate, too.
• Trypsin then activates proelastase and procarboxypeptidase.

[edit] Oligopeptide absorption

• This co transport moves peptides and ?
  • Requires H ions
  • The H-Na antiporter generates the H gradient and uses the Na gradient.
• Peptide absorption kineticall has an advantage over carb absorption.
  • As one peptide is gaken in you get 3 amino acids

Something about energy?

• Absorption of aa is less favorable b/c for every unit of energy you only get one aa.

[edit] Defects in apical aa transporters

• Heartnup disease:
  • Phenylalanine trapsorter is misisng
  • But can absorb peptides with phenylalanine in it.
• Cystinuria

Look it up

[edit] Absorption of water soluble vitamins

• C uses active transport
• B1 has active and passive
• ....
• Folic acid uses facilitated transport.
  • Requires lumenal digestive before it can be absorbed
  • IMportant for nucelic acid synthesis so rapidly dividing cells cannot get enough DNA
• Vitamin B12
  • Uses active transport
  • Requires intrinsic factor
    • Made by parietal cells of the stomach
  • Acts with folic acid to cause similar defects when deficient

[edit] Dietary folate absorption

• Folate essential for thymine and purines
• Found in spinach, beans, and liver
• Megaloblastic anemia occurs b/c protein synthesis works but DNA synthesis is inhibited.
• Folate in food has several glutamic acid attached to it.
  • These must be removed before it can be absorbed.
• Folate in dietary supplements only has one glu on it and can be directly absorbed.
• AGain, peptidases ont eh brush border usually remove the two extra glus on the food folate to allow absorption.
• Once in the cell, the epith cells or the liver will have methyl groups added to make it biochemically active.
• Methyl is added via serine to generate 5,10 met-THF.
  • This form is impt for nucleic acid synthesis.
• CAn also be turned into n5 meth THF so that we can make methionine.
• Methotrexate inhibits DHF reductase and can thus stop nucelic acid synthesis in prolific cells like cancer.

[edit] GAstric intrinsic factor and intestinal vitamin b12 absorption

• Dietary B12 is mostly from proteins in plants.
• Impt coenzyme for homocystein:methionine methyltransferase
  • Makes methionine from 5,10 THF and homocysteine.
• A deficiency in B12, you get the same effects as if you have no folate.
  • Can't make methionine
  • Can't make nucelic acids
• Also get high levels for homocystein
  • Causes increased risk for cardiovascular disease.

• Gastric intrinsic factor
  • Made in stomach
  • Impt for absorption of B12
  • In the stomach, pepsin releases B12 from proteins.
  • Free b12 binds haptocorrin
  • Pancreatic proteases digest haptocurrin in the duod
  • Intrinsic factor then binds b12
  • The complex of Intrinsic factor and b12 is what is absorbed.
  • Inside the cell, b12 is released.
  • B12 then gets moved into the blood
  • Intrinsic factor is required to bind b12 for absorption

[edit] Summary

• Read the slide.

• stopped here on 02/21/11 at 12PM.