B5-096 GI Physiology III Flashcards
what phase of digestion has a large secretion of insulin?
cephalic phase
where are carbohydrates and lipids absorbed?
duodenum > jejunum > ileum
where is iron absorbed?
duodenum
where is folate absorbed?
duodenum
where is calcium absorbed?
primarily duodenum but jejunum and ileum as well
where are bile acids absorbed?
iluem > jejunum, colon > duodenum
where is cobalamin absorbed?
ileum
breaks down carbohydrates at the a 1-4 linkages
a-amylase
can a-amlyase split a1-6 linkages?
no
continued breakdown of carbohydrates after a-amylase is carried out by enzymes at the
brush border
coupled transporter that brings Na+ and glucose into cell
SGLT-1
mediates facilitated diffusion of fructose into cell
GLUT5
mediates monosaccharide efflux into interstial space
GLUT2
lactase splits […]
both monomers are transported via […]
lactose
SGLT-1
- two enzymes
- sucrase moiety splits sucrose/maltose
- isolmaltase activity splits a-limit dextrins/maltose
sucrase-isomaltase
removes glucose monomers for transport
glucoamylase
what do brush border peptidases do?
progressively hydrolyze oligopeptides to amino acids
H/oligopeptide cotransporter
PepT1
there is also a Na/AA cotransporter
the enterocyte can directly absorbs some oligopeptides through […]
these are then disgested to amino acids by […] within the cytoplasm
transporter/ enzyme
PEPT1
peptidases
there is also a Na/AA cotransporter
enterocytes take up 90% of protein resulting in […]
complete lysosomal degradation
M cells take up 10% of protein but half […]
emerges from the membrane intact
package proteins and present them to APCs in interstitium
M cells
endopeptidases
3
- trypsin
- chymotrypsin
- elastase
exopeptidases
2
carboxypeptidases A and B
result in oligopeptides (2-6 AA)
endo or exopeptidases
endopeptidases
result in single amino acids
endo or exo peptidases
exopeptidase
produce peptide with C terminal basic AA
trypsin
produce peptide with C terminal neutral AA
2
chymotrypsin
elastase
what is the advantage of oligopeptide absorption?
think about PepT1
PepT1 moves several AA per turnover = faster absorption
act within the AA chain
endo or exo peptidases
endopeptidase
act on either end of the AA chain
endo or exopeptidases
exopeptidases
hydrolyze TAGs at surface
TAGs from core replace them, causing droplet to shrink
pancreatic lipase
describe the breakdown of emulsion droplets to mixed micelles
- emulsion droplet: pancreatic lipase breaks down TAGs to shrink core
- multilamellar liquid-crystalline: bile salts cause small pieces to bud off into multilamellar vesicle
- unilamellar vesicle- formed by addition of more bile salts to multilamellar vesicle
- mixed micelle: even more bile salts
how to lipids enter enterocytes?
3 ways
mixed micelle crossed into acidic microenviornment to release lipids:
* non ionic diffusion
* incorporation into enterocyte membrane
* carrier-mediated transport
why do the lipids release when the mixed micelle crosses into the acidic microenvironment?
protanation of FFA is favored in the acidic environment
FAT/CD36 does what?
carrier mediated transport of lipids into enterocytes
enterocytes can reform esters to make
apoliproteins and chylomicrons
describe the re-esterfication of lipids into chylomicrons and VLDLs
- LCFA are coverted back to lipids in SER
- fat droplets form in cisternae of SER
- apoliproteins are synthesized in the RER and move to SER to associate with droplets (except Apoli A-1)
- chylomicrons and VLDLs arrive at cis face of Golgi to be glycosylated
- vesicles carrying VLDLs bud off trans-Golgi and move to membrane
- vesicle fuse to membrane to be released
- chylomicrons and VLDLs enter lymph
- enter circulation
Apoli A-1 associated with chylomicrons in Golgi
fatty acids most readily available to us after eating
short and medium chain
produce VLDLs and chylomicrons
enterocytes
after being synthesized in the RER, apoliprotein A moves to
Golgi to associate with chylomicrons
3 parts of folate
pteridine moiety (biologically active)
p-aminobenzoate
glutamate
dietary folate just has more gluatmates
for folate breakdown, brush border peptidases remove
all but one glutamate
becomes PteGlu1
brings PteGlu1 into enterocyte
broken down folate
folate-OH exchanger
critical to serve as methyl donor for DNA synthesis or methionine synthesis
folate
THF is methylated
describe the absorption of cobalamin
- cobalamin bound to nutrients in food
- gastric acid/pepsin release cobalamin from dietary protein
- gastric glands secreted haptocorrin which binds to cobalamin
- gastric parietal cells secrete intrinsic factor
- pancreas secretes proteases and HCO3-
- cobalamin is released after degradation of haptocorrin (duodenum)
- IF-CBL complex forms
- ileal enterocyte absorbs IF-CBL complex
[…] binds cobalamin in somach
haptocorrin
binds cobalamin in duodenum
intrinsic factor
the IF-CBL complex is absorbed in the
ileus
to efflux cobalamin out of enterocyte into interstitial space, it must bind to
trans-cobalamin II
describe active Ca++ absorption
- Ca++ enters via channel
- binds cytoplasmic calbindin or goes into intracellular organelles
- effluxed into interstitial space via Na/Ca exhanger
where does active Ca++ uptake occur
duodenum
predominant paracellular absorption of Ca++ throughout small intestine
passive
active form of vitamin D drives the production of
calbindin
describe the absoprtion of non-heme iron
- Dcytb reduces non-heme iron Fe3+ to Fe2+
- DMT cotransports Fe2+ with H+
- Fe2+ transfers to mobilferrin
- Fe2+ leaves cell via ferroportin and hephaestin oxidizes it to Fe3+
- iron binds to transferrin in plasma
heme iron absorbs at [..] the rate of nonheme iron
10x
why does hephaestin oxidize Fe2+ to Fe3+ ?
- keeps it in interstitial space
- allows to bind to transferrin
describe the absoprtion of heme iron in the duodenum
- Heme Fe2+ enters cell (unknown mechanism)
- Fe2+ transfers to mobilferrin
- Fe2+ leaves cell via ferroportin and hephaestin oxidizes it to Fe3+
- iron binds to transferrin in plasma
short chain and medium chain lipids directly enter
systemic circulation
which zone of the liver has highest oxygen tension?
zone 1
what zone of the liver do beta oxidation and gluconeogenesis occur in?
zone 1
high oxygen demand, greatest area of oxygen
what zone of the liver do lipogenesis, ketogenesis, tryglyceride synthesis and glycolysis occur in?
zone 3
describe the synthesis of bile acid through CYP7A1
cholic acid -> deoxycolic acid -> glycine
cholic acid, deoxycholic acid, and glycine are products of which CYP route?
bile acid synthesis
CYP7A1
describe bile synthesis through the CYP27A1 route
chenodeoxycholic acid -> lithocolic acid -> taurine
chenodeoxycholic acid, lithocolic acid, and taurine are products of which CYP route?
bile acid synthesis
CYP27A1
- bile duct epithelial cells
- protect hepatocytes by transporting bile
cholangiocytes
what conjugates bile salts to bile acids?
bacteria
how much bile acids are reabsorbed?
90-95%
feedback to liver to prevent production of primary bile acids
2
FGF19
recycled bile acids
the production of amino acids produces […] which has to be gotten rid of
ammonia
85% of the circulating […] is taken up by the liver and processed to urea
ammonia
urea is excreted through to kidneys or […] into the colon
recycled
deamination of hepatic amino acids results in
2
glutamate and keto acid
amino group is transferred to alpha-ketoglutarate
the NH4+ that results from the regeneration of alpha-ketoglutarate is consumed in the
urea cycle
ApoB-48
chylomicrons
exogenous lipids to liver
B100
VLDL
rate limiting step of cholesterol synthesis
HMG CoA reductase
why is cholesterol synthesis tightly regulated?
very energy expensive
only two ways to get rid of cholesterol
- secreted in bile acids
- secreted directly into bile duct -> feces
what can the liver do with cholesterol?
3
- excrete in bile
- excrete in feces
- package to VLDLs
moves peptides into intestinal epithelial cells together with a proton supplied by Na/K/H+ exchanger
PEPT1
receptors for B12 are in the […]
terminal ileum
intrinsic factor is made by
parietal cells
moves vitamin B12 into blood
transcobalamin II
individuals who avoid meat/dairy intake have low levels of what vitamin?
B12
non-heme iron transporter
DMT1
functions to remove iron from heme
heme oxygenase
transports iron out of enterocyte
ferroportin
Roux-en-Y causes thaimine deficiency via
diversion of chyme from duodenum to jejunum
can cause thiamine deficiency
3
- Roux-en-Y
- excessive alcohol consumption
- excessive vomiting (especially in pregnancy)
cause a reduction in the sequential breakdown of emulsion droplets
bile acid sequestrants
increase bile acid synthesis in liver and do not decrease bile production
drug class
bile acid sequestrants
a decrease in vitamin D results in a decrease of
calbindin