Normal Digestion And Absorption Part 1

Front 1

Chemical nature of absorbable end-products of the digestion of carbohydrates, proteins and lipids

Back 1

C: Glucose, galactose, fructose
P:
L:

Front 2

Enzymes that digest ingested carbohydrates (plus source, stimuli causing secretion, mechanism(s) of digestion)

Back 2

--Amylase:
*Starch digestion is by pancreatic amylase in small intestine (duodenum)- (amylase also secreted by salivary glands)
*Hydrolyzes internal alpha 1,4 linkages only
*Produces maltose and other oligomers that are then broken down in the brush border of the SI
--Smooth muscle segmentation and peristalsis mixes
pancreatic amylase with chyme and brings the
products of amylase digestion in contact with the
epithelial “brush border” of duodenum and jejunem

Front 3

Epithelial cell mechanisms that enable carbohydrate absorption and importance of sodium transport mechanisms in glucose absorption

Back 3

**Apical membranes of epithelial brush border cells contain three important enzymes for completing starch digestion (End product is glucose): α-dextrinase (isomaltase), sucrase, maltase (glucoamylase)
**Glucose and galactose moved across apical membrane by SGLT1 (Na+ Glu co-transporter), secondary active transport powered by Na gradient created by Na/K ATPase on basolateral membrane (Glut 2 takes glucose (and fructose, galactose) across basolateral membrane into blood)
**Fructose goes across apical by Glut5 facilitated diffusion

Front 4

Describe the cause and consequences of “lactose intolerance.”

Back 4

Lactose --> Glucose + Galactose

Front 5

Enzymes that digest ingested proteins (plus source, stimuli causing secretion, mechanism(s) of digestion)

Back 5

1. PEPSIN -- Stomach (chief cells) -- secreted reflexly by as pepsinogen and converted to pepsin by low pH -- responsible for 15% of protein digestion and inactivated in duodenum by incr pH
2. PROTEASES (secreted by pancreas) -- IN Lumen of small intestine (esp. duodenum and jejunum) AND on brush border of small intestine (due to proteases in epithelial apical membranes) AND within epithelial cells of small intestine after transfer across the apical membrane (due to cytosolic proteases)

Front 6

Describe the state of the pancreatic proteases secreted into the duodenum and the mechanisms by which they are activated.

Back 6

--Proteases secreted as inactive zymogens and proenzymes
--Trypsinogen is activated to Trypsin in apical membrane of brush border by Enteropeptidase (Enterokinase)
--Trypsin then autocatalyzes itself and activates all other

Front 7

Digested forms of dietary protein taken into epithelial cells and why only amino acids are transferred across epithelial cells and the importance of sodium transport mechanisms in the absorption of small peptides and
amino acids

Back 7

--L-amino acids cross apical via Na-AA cotransporters energized by Na gradient (set up by ATPase)
--Most protein absorbed as di- and tri-peptides via PEPT1 transporter in apical membrane that co-transports H+ and peptides using localized H+ gradient set up by Na+/H+ exchanger in apical membrane
--Cytosolic proteases (peptidases) then further break down peptides into AAs in cytosol for facilitated diffusion across basolateral membrane

Front 8

Enzymes that digest ingested lipids (plus source, stimuli causing secretion, mechanism(s) of digestion)

Back 8

***Gastric LIPASE--Small Amt (10-15%) of dig (in stomach) --secreted by chief cells, stimulated by Gastrin -- C1 FA of triglycerides -- pH optimum of 4.0-5.5 - Inactivated in duodenum when acid is neutralized by HCO3- secretion from pancreas
***Pancreatic LIPASE -- most dig. (in duod and jj) -- when chyme in duodenum:
*low pH stimulates incr in SECRETIN -->secr. of panc. juice rich in HCO3 --> raise pH to approx. 7
*Free Fatty acids and small peptides --> incr. Cholecystokinin (CCK), stimulated by I cells --> secr. of panc. juice rich in lipases
*FFAs and small pep --> incr. CCK -->gallbladder contraction + relaxation of sphincter of oddi --> Bile

Front 9

Explain why lipid digestion requires mechanisms that deal with water solubility in addition to digestive enzymes.

Back 9

** Lipids are insoluble in H20 and additional processes are necessary to overcome barriers to lipid digestion produced by H2O insolubility – including emulsification of lipids, secretion of colipase by the pancreas and secretion of bile salts and phosphatidylcholine
(constituents of bile) by the liver.

Front 10

Explain the role of bile salts in (1) lipid digestion and (2) absorption of the end products of lipid digestion.

Back 10

Bile aids lipid assimilation by the action of its two
primary constituents: bile salts and phospholipids
(primarily lecithin)
--Pre-digestion: BS and PL form a boundary around fat
droplets such that the inner core contains the water-insoluble lipid --> stabilizes fat droplets (i.e., sustains their emulsification) --> increases the available surface area of ingested lipids for digestion by lipases.
--Post-digestion: Bile salts generate micelles --Lateral (outside) surface of cylinder is the hydrophilic side of bile salts and inner core is hydrophobic side of bile salts - provides a compartment that can solubilize end-products of lipid digestion.
**Being H2O soluble, micelles readily diffuse through unstirred H2O layer --> brings digested lipid products right up to the apical membranes --> increases conc. gradient across apical membrane --> greatly enhances rate of diffusional uptake
***Enabling property for both actions: Amphipathic!!

Front 11

Describe the special role of co-lipase.

Back 11

*With Micelle formation, bile salts and PLs alter the conformation of PTL (lipase) so that its activity is VERY inhibited (Micelles also physically separate lipids needing digestion from lipases)...
*SO...Colipase (CL), protein co-factor, binds to PTL to form a CL-PTL complex, functionally activating PTL so that it can digest TGs
**Anchors the complex in the lipid droplet water interface (brings PTL close to TGs) -- Causes conformational change of the PTL molecule to expose the substrate binding site -- Removes the inhibitory effect of bile salts and phospholipids on PTL activity.
**CL is secreted by pancreas in an inactive form called procolipase --> Converted in the intestinal lumen into the active form - colipase - by trypsin. Trypsin cleaves a pentapeptide from the N-terminus.
*PTL often called Colipase-dependent Lipase (Chronic absence of colipase reduces TG digestion by 50-60% --> steatorrhea)

Front 12

Compare the molecular forms of ingested lipids that enter intestinal epithelial cells with those that leave these cells to go into lymph and describe the processes within epithelial cells that effect these changes.

Back 12

*FFAs, monoglycerides, lysolethicin, cholesterol and fat-soluble vitamins all cross apical by simple or carrier-mediated diffusion
*Inside the epithelial cell all products of digestion are
re-esterified into their parent compounds
*Re-esterified lipids + apoprotein B coalesce into chylomicrons that cross the basolateral membrane.

Front 13

Name the substrates and end-products of colonic digestion by anaerobic bacteria, describe the chemical process by which they carry out digestion, and describe the mechanisms by which colonic epithelia absorb the end-products of bacterial digestion.

Back 13

*Predominant substrate: Undigested carbohydrates (“fiber”) – the resistant starches (RS) and the non-starch polysaccharides (NSP).!
*Two-step Process: Bacterial secretion of digestive enzymes into fecal fluid --> breakdown RS and NSP to glucose and other monosaccharides (no SGLT1 or GLUT transporters in colon) THEN Bacterial uptake and fermentation of glucose to: short chain fatty acids (SCFA): acetic, propionic and butyric acids AND gases: predominantly H2 and CO2
*About 10% of undigested carbohydrates is converted
**SCFAs are absorbed by colonic epithelia via Non-ionic diffusion AND via SCFA-HCO3 exchanger in both apical and BL membranes
**Absorption of SCFAs promotes electrolyte and H2O
absorption - apical SCFA-HCO3 exchanger works with apical Na-H and SCFA-HCO3 exchangers to absorb Na+ and Cl- H2O follows --> Reduction in colonic digestion can produce diarrhea!

Front 14

Pancreatic Lipases: Pancreatic Triglyceride Lipase

Back 14

--Pancreatic Triglyceride Lipase--
a. by far, the most predominant pancreatic lipase – often just called “pancreatic lipase.”
b. secreted by the pancreas in active form BUT not functionally active until pancreatic colipase binds to it.
c. acts specifically on triglycerides: cleaves FA from 1 & 3 positions of triglycerides 2FFA + 2-monglyceride.
d. Absence of PTL: 50-60% of dietary TGs are not digested and absorbed --> feces with high fat content --> Steatorrhea: feces with abnormally
high fat content – pale, oily, smelly!

Front 15

Pancreatic Lipases: Pancreatic Cholesterol Esterase (Cholesterol Ester Hydrolase)

Back 15

--Pancreatic Cholesterol Esterase--
a. secreted by the pancreas in active form BUT not functionally active in intestine until it interacts with bile salts.
b. primary action: cleaves FFA from cholesterol ester & other sterols
c. not a very specific lipase:
• cleaves FFA from esterified fat-soluble vitamins (A, D, E, K) AND cleaves FFA from di- & monoglycerides
FFA + glycerol

Front 16

Pancreatic Lipases: Phospholipase A2

Back 16

Phospholipase A2:
a. secreted by the pancreas as a proenzyme and converted to active enzyme by trypsin in small intestine.
b. primary action: hydrolyzes fatty acid in the C2-position of phospholipids.
---Lecithin --> Lysolethicin