Digestion and Absorption Flashcards
Remember that the stem cells of the GI tract are located in the intestinal crypts and they migrate up the villi to differentiate into enterocytes, goblet cells, or endocrine cells. Also cells can migrate down the villi to differentiate into pana cells, defense cells
Remember that cells in the crypts are mostly secretory and the cells in the villus are more absorptive
T or F. There is a very high proliferation rate in the intestine
T. Very 3-5 days all cells will replace themselves as a protective mechanism against damage/mutation
Trypsin breaks carboxyl terminal bonds of basic peptides like arginine and lysine
chymotrypsin breaks N-terminus bonds of aromatic AA bonds (elastase is similar but broader)
Note that there are two main categories/locations of digestion in the Gi tract, lumenal digestion which is mediated by secreted enzymes mainly from the pancreas, and membrane-digestion which is mainly mediated by brush-border dissaccharidases such as maltase, sucrase, lactase, etc.
What are the main layers/barriers that a molecule must pass to be absorbed from the GI tract?
- The undisturbed mucosal layer
- The glycocalyx layer
- The epithelium, cytoplasm, and then basolateral membrane
What are the main mechanisms of GI absorption?
1) Pinocytosis- simple invagination of the epithelium of the villi (very little). Note that proteins mostly arent absorbed by the small intestine, but those that are, are mediated by pinocytosis
2) Passive diffusion via paracellular (leakly in small intestine) routes for only some molecules (semi-permeable)
3) Facilitated diffusion
4) Active transport (Na, sugars, AAs)
How does the GI respond to starvation or resection?
During starvation the villi shorten and some digestive enzymes do not proliferate, but during resection you will initially see undernutrition but the remaining tissue will expand and adapt
Malnutrition doesnt really occur until 70% of the small intestine is removed/damaged
Digestion of carbs
Luminal digestion of carbs is mediated by salivary a-amylase in the mouth (break a1,4-glycosidic bonds to form maltose, maltotriose, and limit dextrin) and pancreatic a-amylase in the small intestine
Membrane digestion is mediated by glucoamylase, sucrase, isomaltase, lactase, and trehalase
Note that the body has a very high carb digestive capacity so that pretty much everything we eat is digested
What are the main products of GI digestion to be absorbed?
glucose
galactose, fructose
The vast majority of glucose absorption is aerobic and via active transport
How is glucose absorbed from the GI lumen?
1) SGLT 1, which is a Na/Glucose co-transporter that depends on a gradient of sodium which is maintained by active sodium transporters on the BL membrane
2) GLUT 2-BL (glucose, galactose, and fructose) and 5-apical (glucose and fructose). These are Na independent (more facilitated than active)
These have a VERY high absorptive capacity (and is not very regulated- dont overdo it)
Sucrase-Isomaltase normally presents in children because they only express lactase in early childhood and then switch primarily to sucrase-isomaltase expression and this can occur when the timing messes up
A: Normal
B: Absence of SGLT2
C: Overall impaired absorption
How much protein are adults exposed to on a normal day?
About 100g dietary and another 40g from secretions, cellular degeneration, etc. Note that all of this is acted upon by proteases in the GI lumen
How is trypsinogen secreted from the pancreas activated?
Once it reaches the duodenum, enterokinase from duodenal cells cleaves a 6 AA residue from the C-terminal end to produce active trypsin. Trypsin then activates the other pancreatic enzymes, as well as more trypsin
What predominantly causes acute pancreatitis? Chronic?
Acute: Biliary obstruction and alcohol
Chronic: alcohol
What is the mechanism of pancreatitis?
there is premature activation of trypsin in the pancreas caused by interaction of trypsinogen with pancreatic lysosomes (which contain enterokinase) or genetically due to a R117H mutation (prevents inactivation/stabilizes) that causes pancreatic destruction
There are many types of free AA transporters including Na dependent transporters, PAF proteins (driven by NHE) and facilitated diffusion as well, specific for basic, acidic, neutral AAs
Large peptides are broken down further by brush border peptidases
Note that the absorptive capacity of di- and tripeptides is greater than that of free AAs suggesting seperate carrier systems for them, predominantly in the proximal intestine (whereas free AA transporters are more clustered in the distal small intestine). These are coupled to NHE
Note that if you present arginine as a dipeptide it will be absorbed better b/c its absorbed using a different transporter
How is fat absorbed?
This requires the presence of bile and lipases and emulsification (breaking down for action with lipases). Lipases include gastric lipase (breaks down the fatty acid/glycerol bond at position 3) producing diglycerides
Monoglycerides and free fatty acids can be absorbed
What are the products of lipids being hydrolyzed by lipases?
cholesterol
fatty acid
monoglycerides
What happens to the monoglycerides, fatty acids, and cholesterol?
They form mixed micellese are diffuse across the lumenal membrane via passive diffusion (may be facilitated), but the entire micelles are not absorbed all together so the carriers may be different
Once in the cytosol, these particles are insoluble again and are transported by binding to fatty acid binding proteins to the smooth ER where the triglycerides are re-synthesized using acyl CoA and ATP and then packaged into chylomicrons
How are chylomicrons produced in the small intestine?
They are composed of mostly TAGs and they are formed via 2 parts:
1) Formation of a particle 1 (Apo-B + core lipid) formed in the RER
2) Particle 2 is formed in the SER
3) These particles combine to form a pre-chylomicron
The pre-chylomicron that budds of the ER using a PCTV and acquires a Apo-A1 in the golgi, and then is exocytosed into lymph (not blood like carbs and proteins)
