digestion and absorption mechanism of nutrient absorption Flashcards
what is digestion?
the breakdown of large molecules into small molecules which can then be absorbed
what are proteins broken down into?
amino acids, di and tri peptides
what are brush border enzymes attached to?
the luminal membrane of the small intestinal cells
what are polysaccharides broken into?
monosaccharides
polysaccharide vs disaccharide breakdown
polysaccharides mainly by salivary amylase and pancreatic enzymes
disaccharides mainly by brush border enzymes
what is a triglyceride made of?
a back bone of glycerol with 3 fatty acids attached by ester bonds
what are triglycerides broken into?
2 free fatty acids and a monoglycerides
what does incomplete digestion result in?
malabsorption
what are triglycerides broken down by?
gastric lipase (minor), mainly pancreatic lipase, also bile salts
what are the methods of absorption?
- simple diffusion
- carrier-mediated (amino acids and sugars) — secondary active and facilitated diffusion
- (receptor-mediated) endocytosis — vit B12 and intrinsic factor (both produced by stomach parietal cells) and cholesterol
what are the different sites of absorption?
- mouth, oesophagus, stomach — limited diffusion
- duodenum and jejunum - MAJOR SITE
- ileum
- colon
- rectum - limited diffusion
what is absorbed in the ileum?
vit B12, bile salts and K+ (all in terminal ileum)
what is absorbed in the colon?
Na+, some H2O, and short chain fatty acids
describe the sublingual and suppository routes of drug delivery
- avoid 1st pass metabolism by the liver
- mouth and rectum — the blood at these sites of absorption goes straight to heart instead of liver via portal vein
what is the total SA of the SI?
200 m2
what does a decreased SA lead to?
malabsorption
what transport proteins are expressed on the apical/brush border membrane for glucose and galactose transport?
SGLT1 - mediate Na+ dependent co-transport of glucose and galactose
what generates the sodium gradient for the movement of glucose and galactose into the cell?
NaK ATPase on the interstitial membrane
what does the sodium gradient enable in CHO absorption?
sodium gradient is used to drive glucose transport into the cell, so it can move in against its conc gradient throguh SGLT1- secondary active transport process
what is secondary active transport? what is an example of primary active transport?
against a conc gradient, energy derived from Na+ gradient created by Na+ pump
Na+ pump = primary active transport
what is absorbed along with glucose?
sodium
what happens as glucose accumulates in cell?
sets up a conc grad — allows glucose to leave the cell via glucose transporters (GLUT2) = facilities diffusion
via what does fructose enter and leave the cell?
enters via GLUT5 and leaves via GLUT2
what does GLUT4 have a dependency for?
insulin
what does a lack of transporters result in?
malabsorption
describe glucose-galactose malabsorption syndrome
- genetic disease
- SGLT1 (glucose transporter on apical membrane) mutated = no absorption of glucose or galactose
- severe and potentially fatal diarrhoea in infants (manifests early, lack nutrition and become dehydrated rapidly)
- treatment = avoid glucose and galactose
how many dietary amino acids are there?
20
50% of amino acids are absorbed as di and tri peptides by what?
PepT1
other 50% by specific transporters
what happens to peptides in enterocyte?
hydrolysed to amino acid (released into blood as aa)
name some amino acid specific transporters. superfamily?
PepT1 uses what gradient for transfer of peptides across the membrane?
H+ gradient — cotransport
alanine transport?
Bo cotransport — alanine and Na+
XAG- transproter?
what is Hartnup disease?
a rare genetic disease — B0 transporter affected
what is cystinuria?
an inherited condition characterized by a buildup of the amino acid, cystine, in the kidneys and bladder. This leads to the formation of cystine crystals and/or stones which may block the urinary tract.
B0 transproter is affected
fat digestion problems leads to deficiencies in which vitamins?
K, A and D
what enzyme mainly influences fat digestion?
pancreatic lipase
what are the 2 major roles of bile salts?
- emulsification of large fat droplets to increase the SA for action of lipase
- formation of mixed micelles = stabilises products of triglyceride hydrolysis (monoglyceride and fatty acids) while they are ‘translocated’ to apical membrane
what do mixed micelles consist of?
monoglcyerides, fatty acids, bile slats, phospholipids and cholesterol
what does a lack of bile result in?
steatorrhoea
what is the average dissociation constant of free fatty acids? what does this mean?
pKa of 4.9
means that at a pH of 4.9, 50% of the fatty acids will be in the undissociated form (simple diffusion is possible in the undissociated form)
if you go more acidic than 4.9, more than 50% will be in the undissociated form, opposite for above 4.9 (more alkali)
what is the pH of the lining/wall of the SI?
pH 6.5 (slight acidity) — therefore few FFAs in the undissociated state
name 2 fatty acid transporters
FAT (fatty acid transproter) + CD36
SFCA (short chain fatty acid) transporters in colon
what happens after fatty acids and monoglycerides are absorbed?
- triglycerides resynthesised in endoplasmic reticulum and packaged into chylomicrons
- chylomicrons then leave by exocytosis
- chylomicrons transproted in lymphatic system to liver (lacteal)
where is cholesterol absorbed?
duodenum
what is cholesterol absorption largely dependent on?
Niemann-Pick C1-Like 1 (NPC1L1) protein
what does NPC1L1 enable?
receptor-mediated endocytosis in cholesterol absorption
what does ezetimibe do?
inhibits cholesterol endocytosis — decreases plasma cholesterol
can be used in combination with statins or when statins aren’t tolerated
name 3 short chain fatty acids
butyrate, propionate, acetate
describe SCFA
- not major component of diet
- produced by bacterial fermentation of undigested polysaccharides in the colon
what are SCFAs absorbed with and via what?
with Na+ via the sodium co transproter called the SMCT1
what are SCFAs mainly used by the colonocyte for?
intracellular metabolism
what enhances health of colon epithelium and may help prevent colon cancer?
butyrate
bacteria that mainly produce _____ are much better for you than ____ and _____
- butyrate
- proprionate and acetate
via what does water move across the wall of the SI?
osmotic gradient
what is the osmotic gradient mainly created by?
the absorption of gradients
how many litres of water are absorbed each day?
8.4 L
(6.5L in SI whereas only 1.9L in colon)
route for H20 absorption in SI?
- via junctional complexes between cells
- via SGLT1 and aa transporters
- NOT aquaporin water channels
what enters the gut via saliva (mouth)?
NaCl
what enters the gut via the stomach (gastric secretion)?
HCl
what enters the gut via pancreatic and bile secretion (duodenum)?
HCO3-
what enters the gut in the jejunum?
NaCL
what enters the gut in the ileum?
HCO3-
what enters the gut in the colon?
K+ and HCO3-
what transporters are present in the jejnumum and ileum?
Na/glucose or Na/amino acid cotransporters
what exchanger is present in the duodenum and jejunum?
Na-H exchanger
what exchangers are present in the ileum and proximal colon?
parallel Na-H and Cl-HCO3- exchangers
what channel is present in the distal colon?
epithelial Na+ channel
what are sodium channels in the distal colon regulated by?
steroid hormone called aldosterone — increases sodium absorption in the colon
what has no active absoprtion in the SI or LI?
HCO3-
how is K+ absorbed in the ileum?
para cellular diffusion
K+ in the LI?
predominantly secretion
concentrations of K+ and HCO3- in faeces?
quite HIGH
[K+] = 90 mM
[HCO3-] = 30 mM
what does severe/chronic diarrhoea lead to?
hypokalaemia and metabolic acidosis
what does an increased osmotic load in the colon lead to?
increased fluid in faeces — diarrhoea
what causes increased osmotic load?
incomplete digestion and absorption of food
- lack of enzymes or transporters
- damage to mucosal cells
secretion of ions by gut
- enhanced secretions of NaCl (esp in SI) — oversaturated the capacity to reabsorb fluid
describe lack of enzymes or transporters causing diarrhoea
- congenital (neonate) = ‘watery’
- glucose-galactose malabsorption (SGLT1)
- lactase deficiency - disease of pancreas and biliary systems = steatorrhoea — fats passed into LI where it is metabolised by bacteria — flatulence — abdominal pain and foul smelling stool
- pancreatitis, cystic fibrosis
- hepatitis, gall stones
what autoimmune disease can cause damage to mucosa?
coeliac disease and chron’s disease
effects of shigella and campylobacter
bacteria (shigella and campylobacter) cause destruction of intestinal wall (decreases SA) —> blood in faeces (dysentery)
effects of salmonella
inflammation —> chronic diarrhoea
what are the main causes of diarrhoea in the UK?
rotavirus and norovirus
describe vibrio cholera, some strains of E. Coli and rotavirus infections
secretions of ions by gut
- toxin produced by bacteria which “hi-jacks” normal cellular processes
- intestinal cells normally secrete H2O 9togegtehr with mucus and HCO3-) — roughly 1 litre a day
- in cholera secretion exceeds 20 litres a day
- toxins may also inhibit sodium absorption BUT not SGLT1 — basis of oral rehydration therapy
name the fat vs water soluble vitamins
fat soluble = vitamins A/D/E/K
water soluble = B group and C vitamins
how are fat soluble vitamins absorbed?
facilitated diffusion and/or endocytosis at physiological concentrations
what does the absorption of fat soluble vitamins require? clinical significance?
optimal fat digestion — means what people with pancreatic and biliary disease have deficiencies in these vitamins (esp vit K which doesnt have large stores in the body)
how are water soluble vitamins absorbed? exception?
have specific transporters (facilitated and secondary)
exception is B12 — endocytosis — requires intrinsic factor secreted from parietal cells in the stomach which binds to B12 - this complex is then absorbed via endocytosis
vitamin C has a specific transporter coupled to what?
Na+ entry
what 2 routes can Ca++ absorption in the SI occur by?
trans cellular and paracellular
which route for Ca++ absorption in the SI is regulated by vitamin D?
transcellular
calcium enters the cell apical membrane by what channel?
TRPV6
TRPV5 vs V6
both for calcium absorption
V5 - kidney
V6 - SI
what does Ca++ bind to once in the cell?
calbindin
why does Ca++ have to bind to something in the cell?
high concentrations of calcium in the cell can be bad for the cell
functions of calbindin binding
- sequest Ca++ out of cytoplasm
- enable Ca++ movement from apical to basolateral membrane
how is Ca++ removed from the cell at the basolateral membrane?
by active transport using PMCA (plasma membrnae Ca++ ATPase)
describe PMCA
expends ATP to pump out Ca++ in exchange for H+ coming in
what regulates calcium absorption?
the active form of vitamin D (1,25 - dihydroxy-vitamin D)
what does the active form of vitamin D do?
binds to intracellular receptors which trigger transcription of mRNA. mRNA transcribed codes for 3 proteins:
• TRPV6 channel
• calbindin protein
• PMCA
each of these proteins are upregulated by vitamin D to increase Ca++ absorption
where does iron absorption occur?
duodenum
what kind of transport process is iron absorption?
transcellular (has to cross apical and basolateral membranes)
at the apical membrane, via what 2 mechanisms can iron enter the cell?
- divalent metal transporter (DMT) - transports ferrous/reduced form of iron at the same time as protons — secondary active transport
- iron can also be absorbed in the form of heme (we don’t know how this crosses membrane) - heme oxidised once in cell to release iron in the form of ferric iron — then reduced to ferrous iron
once oxidised what does the remained of the heme protein go to produce?
biliverdin = precursor to bilirubin (excreted in bile)
once in the cell, the ferrous irons are potentially toxic so must be bound to what?
a protein called mobilferrin
what does mobilferrin do?
sequesters the iron out of the cytoplasm and facilitates its movement from the apical to basolateral membrane
how does iron leave the cell at the basolateral membrane?
via facilitated diffusion in a transporter called ferroportin 1 (FP1)
what happens to the ferrous iron once released from the cell?
reoxidised to ferric irons which can then bind to the plasma transport protein = plasma transferrin
the oxidation of ferrous to ferric iron once outside of the cell is mediated by what?
hephaestin (located at basolateral membrane)
name the hormone that regulates iron absorption
hepcidin
what produces hepcidin and when?
- produced by liver cells
- produced when there is plenty of iron in the body
what does hepcidin do/result in?
binds to ferroportin — results in the internalisation of ferroportin transporters — decreased ferroportin transporters — inhibit exit step in absorption, entry step continues
therefore iron gets stored in enterocytes bound to mobilferrin, but within a day or 2 the enterocytes slough off in the villus tip into the lumen of the intestine — iron lost from the body with faeces
what happens if you are deficient in iron?
- reduced hepcidin release
- more ferroportin in membrane
- enhances rate of iron absorption
