Unit 6 - Intestinal Transport II: Nutrients

Question 1

are the following endopeptidases or exopeptidases?

• trypsin
• chymotrypsin
• elastase
• carboxypeptidase

Answer 1

endopeptidases: trypsin, chymotrypsin, elastase
exopeptidase: carboxypeptidase A/B

Question 2

what is the “trigger” for pepsin activation?

Answer 2

enterokinase converts trypsinogen to trypsin, which then activates:

• trypsinogen –> trypsin
• chymotrypsinogen –> chymotrypsin
• proelastase –> elastase
• procarboxypeptidase A/B –> carboxypeptidase A/B

Question 3

how thoroughly does lumenal protein digestion occur?

Answer 3

40% free AA

60% peptides (2-6 residues)

Question 4

what kinds of people can absorb proteins other than mono, di, or tripeptides?

Answer 4

• newborn infants (globulins and whole PRO can be absorbed)

- people with certain food allergies (whole PRO absorbed by pinocytosis at base of microvilli)

Question 5

how are monopeptides absorbed compared to di/tri/tetrapeptides?

Answer 5

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

Question 6

what are some characteristics of carrier-mediated AA transport?

Answer 6

1. AA transport is sterospecific with L-isomers preferentially absorbed over D-isomers
   - although symport properties predict equality
2. AA can be concentrated via concentration gradient (proven via everted hamster intestine experiment)
3. most AA need inward Na+ concentration gradient for concentrative uptake
   - if no Na+, very little is absorbed
4. rate of transport of AA reaches plateau value when [AA] varies
   - transport determined by Vmax and Km

Question 7

how do Vmax and Km contribute to transport kinetics?

Answer 7

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

Question 8

on the brush border membrane, which substrates are Na+ dependent or independent?

Answer 8

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

Question 9

on the basolateral membrane, which substrates are Na+ dependent or independent?

Answer 9

need Na+

• small neutral AA
• 3-4 carbon neutral AA

don’t need Na+

• neutral AA with hydrophobic side chains
• basic AA

Question 10

what is the “kinetic advantage” of peptide absorption?

Answer 10

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

Question 11

what happens in Hartnup disease? what AA are affected the most?

Answer 11

“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)

Question 12

what happen sin cystinuria? what AA are affected the most?

Answer 12

“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

Question 13

how is digestion of starch begun?

Answer 13

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

Question 14

what are the starch digesting enzymes on the brush border?

Answer 14

lactase, maltase, sucrase, and isomaltase

Question 15

what is the mechanism of transport for sugars?

Answer 15

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

Question 16

why does lactose cause osmotic diarrhea?

Answer 16

lactose is osmotically active

Question 17

what is the lactose tolerance test?

Answer 17

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)

Question 18

what is glucose-galactose malabsorption?

Answer 18

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

Question 19

what does presence of fat in duodenum cause release of?

Answer 19

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

Question 20

how does digestion of fats start and continue?

Answer 20

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

Question 21

is lipase fat or water soluble?

Answer 21

it is water soluble like all lumenal enzymes of digestion

Question 22

what does colipase do?

Answer 22

anchors lipase to micelles to provide access to neutral TGs inside micelles

Question 23

what do 2-MAGs sometimes isomerize to?

Answer 23

1- or 3-MAGs that are converted by lipase to glycerol

Question 24

how small are fat globules emulsified?

Answer 24

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

Question 25

what kinds of FA can diffuse directly to portal blood?

Answer 25

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

Question 26

what does fatty acid-binding PRO do?

Answer 26

cytosolic PRO that binds to LCFA in enterocyte

• minimizes reflux back into intestinal lumen
• ensures transfer of FA up to SER for re-esterification

Question 27

what does the enterocyte re-esterify?

Answer 27

absorbed monoglycerides, lisophospholipids, cholesterol, and LCFA

Question 28

what is necessary for cholesterol absorption? what blocks it?

Answer 28

Niemann-Pick C1 like (NPC1L1) transporter

-Ezetimibe inhibits this transporter to lower cholesterol

Question 29

formation of chylomicrons

Answer 29

1. LCFA and other products of lipid digestion are converted back to TGs, PLs, and esters of cholesterol in SER
2. fat droplets form in cisternae of SER
3. apoPRO are made in RER, then transferred to SER, where apoPRO associate with lipid droplets
4. nascent chylomicrons and VLDLs arrive at cis face of Golgi, and apoPRO are glycosylated
5. vesicles with chylomicrons or VLDLs bud off from trans-Golgi apparatus and move to basolateral membrane in transport vesicles
6. transport vesicles fuse with basolateral membrane, releasing chylomicrons or VLDLs
7. chylomicrons and VLDLs pass thru large interendothelial channels of lymphatic capillaries and enter lymph

Question 30

how are chylomicrons transferred from lymph to blood?

Answer 30

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