Unit 6 - Intestinal Transport II: Nutrients Flashcards
are the following endopeptidases or exopeptidases?
- trypsin
- chymotrypsin
- elastase
- carboxypeptidase
endopeptidases: trypsin, chymotrypsin, elastase
exopeptidase: carboxypeptidase A/B
what is the “trigger” for pepsin activation?
enterokinase converts trypsinogen to trypsin, which then activates:
- trypsinogen –> trypsin
- chymotrypsinogen –> chymotrypsin
- proelastase –> elastase
- procarboxypeptidase A/B –> carboxypeptidase A/B
how thoroughly does lumenal protein digestion occur?
40% free AA
60% peptides (2-6 residues)
what kinds of people can absorb proteins other than mono, di, or tripeptides?
- newborn infants (globulins and whole PRO can be absorbed)
- people with certain food allergies (whole PRO absorbed by pinocytosis at base of microvilli)
how are monopeptides absorbed compared to di/tri/tetrapeptides?
monopeptides: Na+/AA cotransproter into lumen
di/tri/tetrapeptides: H+/(AA)n cotransporters (PepT1) into lumen
-(AA)n further broken down into AA by tripeptidases and dipeptidases
what are some characteristics of carrier-mediated AA transport?
- AA transport is sterospecific with L-isomers preferentially absorbed over D-isomers
- although symport properties predict equality - AA can be concentrated via concentration gradient (proven via everted hamster intestine experiment)
- most AA need inward Na+ concentration gradient for concentrative uptake
- if no Na+, very little is absorbed - rate of transport of AA reaches plateau value when [AA] varies
- transport determined by Vmax and Km
how do Vmax and Km contribute to transport kinetics?
Vmax - determined by number of transporters in membrane and turnover time of single transporter
- saturation kinetics implies limited number of transport sites
- free diffusion would be linear, and not show a plateau
- kinetics are analogous to Michaelis-Menten
on the brush border membrane, which substrates are Na+ dependent or independent?
need Na+
- neutral (aromatic and aliphatic)
- phe and met
- acidic (glu, asp)
- imino (pro, hydroxy-pro)
don’t need Na+
- basic AA
- neutral AA with hydrophobic side chains
on the basolateral membrane, which substrates are Na+ dependent or independent?
need Na+
- small neutral AA
- 3-4 carbon neutral AA
don’t need Na+
- neutral AA with hydrophobic side chains
- basic AA
what is the “kinetic advantage” of peptide absorption?
if gly is present in lumen as free AA, then the enterocyte absorbs only thru apical AA transporters
- if same gly is present as dipeptide gly-gly, then rate of appearance in blood is 2x as high
- thus, PepT1 is an effective mechanism for “absorbing” AA
what happens in Hartnup disease? what AA are affected the most?
“system B” apical membrane AA transporter is defective
- absorption of neutral AA (like L-phe) is reduced in both intestines and kidneys
- excessive amounts of trp are excreted in urine (important precursor for serotinin, melatonin, and niacin)
what happen sin cystinuria? what AA are affected the most?
“system B0+” apical membrane AA transporter is defective
- absorption of L-cystine and basic AA is reduced
- in kidney, affected patient has inadequate absorption of cystine, causing kidney stones
how is digestion of starch begun?
ingested CHO is 60% starch, 30% sucrose, 10% lactose
- salivary amylase (ptyalin) starts conversion of starch to sugar
- -has optimum pH of 6.7, and inactivated in stomach
- most starch broken down in intestine by pancreatic amylase
what are the starch digesting enzymes on the brush border?
lactase, maltase, sucrase, and isomaltase
what is the mechanism of transport for sugars?
facilitated diffusion or Na-coupled cotransport
- SGLT1 - Na+ coupled for glucose or galactose to enter enterocyte
- GLUT5 - facilitated diffusion of fructose to enter enterocyte
- GLUT2 - mediates efflux of all across basolateral membrane into interstitial space
why does lactose cause osmotic diarrhea?
lactose is osmotically active
what is the lactose tolerance test?
if give lactose…
- plasma glucose will not rise as much as if given glucose
- H2 will be present in breath due to colonic bacteria metabolizing the lactose that enters the colon (takes 8 hours)
what is glucose-galactose malabsorption?
rare genetic disease (only 100 patients reported) where SGLT1 are missing or defective
- accumulation of glucose and galactose in intestines causes diarrhea, dehydration, death
- patients die soon after birth unless diagnosed properly
- no cure, but treat with restricted diet to fructose-based solid diet
what does presence of fat in duodenum cause release of?
GIP (to decrease gastric acid secretion) and CCK
- slows gastric motility and emptying
- stimulates pancreatic enzyme secretion
- stimulates intestinal fluid secretion
- stimulates GB contraction
- relaxes sphincter of Oddi
how does digestion of fats start and continue?
starts with lingual lipase, and continues with gastric lipase and food-bearing lipase with acidic pH optima
- digestion mostly in jejunum, completed by mid-jejunum via:
- -pancreatic phospholipase A2
- -cholesterol esterase
- -pancreatic lipase
is lipase fat or water soluble?
it is water soluble like all lumenal enzymes of digestion
what does colipase do?
anchors lipase to micelles to provide access to neutral TGs inside micelles
what do 2-MAGs sometimes isomerize to?
1- or 3-MAGs that are converted by lipase to glycerol
how small are fat globules emulsified?
fats separate from aqueous phase of chyme as globules about 1 micron in diamter
- bile salts, FA, and PL emulsify into smaller micelles 30-100 Angstrums in diameter
- micelles have negative surface charge, so mutual charge repulsion stabilizes emulsion
what kinds of FA can diffuse directly to portal blood?
short-chain FA (up to 12 carbons), b/c more hydrophilic than the rest
-the enterocyte doesn’t re-esterify them, so directly transferred to portal blood
what does fatty acid-binding PRO do?
cytosolic PRO that binds to LCFA in enterocyte
- minimizes reflux back into intestinal lumen
- ensures transfer of FA up to SER for re-esterification
what does the enterocyte re-esterify?
absorbed monoglycerides, lisophospholipids, cholesterol, and LCFA
what is necessary for cholesterol absorption? what blocks it?
Niemann-Pick C1 like (NPC1L1) transporter
-Ezetimibe inhibits this transporter to lower cholesterol
formation of chylomicrons
- LCFA and other products of lipid digestion are converted back to TGs, PLs, and esters of cholesterol in SER
- fat droplets form in cisternae of SER
- apoPRO are made in RER, then transferred to SER, where apoPRO associate with lipid droplets
- nascent chylomicrons and VLDLs arrive at cis face of Golgi, and apoPRO are glycosylated
- vesicles with chylomicrons or VLDLs bud off from trans-Golgi apparatus and move to basolateral membrane in transport vesicles
- transport vesicles fuse with basolateral membrane, releasing chylomicrons or VLDLs
- chylomicrons and VLDLs pass thru large interendothelial channels of lymphatic capillaries and enter lymph
how are chylomicrons transferred from lymph to blood?
once vesicles fuse with basolateral membrane and contents pass thru membrane by exocytosis are picked up by lymphatic system, the lymph delivers chylomicrons to blood thru thoracic duct
