digestion and absorption of nutrients (lecture series) Flashcards
What are proteins broken down (digested) into ?
- amino acids
- dipeptides
- tripeptides
What are carbohydrates (polysaccharides) broken down (digested) into ?
monosaccharides
Where are the enzymes found that digest proteins?
- stomach
- pancrease
- brush border
Where are the enzymes found that digest carbohydrates?
- saliva
- pancreas
- brush border
Where are the enzymes found that digest fats?
- stomach
- pancreas
- bile salts
What are fats (triglycerides) broken down (digested) into ?
- free fatty acids
- glycerol (monoglycerides)
What is another name for carbohydrates ?
polysaccharides / disaccharides
What is/causes malabsorption ?
incomplete digestion of large molecules into smaller ones (e.g proteins into amino acids)
How does malabsorption cause diarrhoea ?
- incomplete digestion
- large molecules continue to move through GI tract
-
large molecules draw water with them
= stool is loose
What are the main methods of absorption ?
- simple diffusion
- carrier mediated (facilitated diffusion, secondary active transport)
- receptor-mediated endocytosis (vit B12, intrinsic factor, cholesterol)
Where does the majority of absorption take place ?
duodenum
jejunum
Which substances are absorbed in the terminal ileum ?
- vitamin B12
- bile salts
- potassium
Which substances are absorbed in the colon ?
- sodium
- some water
- short chain fatty acids
Which sites in the GI tract are only involved in very limited absorption of nutrients ?
- mouth
- oesophagus
- stomach
- rectum
What is the benefit of delivering drugs via mouth or rectum?
the blood supply from these areas go to the heart whereas the blood from the intestines go via the liver
What are the 2 main features of the small intestine that make it the major site of absorption ?
- surface area (200m^2 total area)
- polarised expression of transport proteins used in absorption
What features of the small intestine create such a large surface area?
- Plicae circularis/folds of kerckring= circular folds in the wall
- villi
- microvilli = “brush border”
What does “polarised expression of transport proteins” mean ?
there are different ion transports on each side of the cell meaning that a gradient can be formed
What is another name for co-transport ?
secondary active transport
What drives co-transport/secondary active transport ?
usually, an Na gradient created by the sodium-potassium pump on the opposite membrane
What physical problems can cause malabsorption ?
- indigestion (lack of enzymes)
- decreased surface area
- lack of transporters
What is the co-transport protein for glucose called ?
SGLT1 protein
What is the protein transporter for fructose called that’s in the apical intestinal membrane ?
GLUT5
What is the protein transporter for fructose called that’s in the basement intestinal membrane ?
GLUT2
What is glucose-galactose malabsorption syndrome ?
- genetic disease
- SGLT1 mutation (glucose co-transporter protein on apical membrane)
= cannot absorb glucose or galactose in the intestines
How does glucose-galactose malabsorption syndrome manifest/present in infants?
Severe/potentially fatal diarrhoea
= child becomes malnourished and quickly dehydrated
What is the treatment for glucose-galactose malabsorption syndrome ?
- avoid glucose and galactose in diet
- provide child with nutrients via other methods
How many dietary amino acids are there ?
20
What % of amino acids are absorbed as tri/dipeptides ?
50%
Which transporter is used in the absorption of tri/dipeptides in the intestines ?
PepT1
What happens to tri/dipeptides once they’re absorbed into the cell from the intestine ?
hydrolysed into amino acids, so leave into blood as amino acids
What method of transport does the PepT1 transporter use ?
co transport / secondary active transport
(uses a H gradient rather than Na)
What would cause amino acids in the urine ?
rare genetic diseases that affect protein transporters, resulting in malabsorption
Which enzyme mainly influences lipid digestion ?
Pancreatic lipase
some gastric lipase has a minor role
What substance is the digestion of lipids dependant on ?
bile salts
Are bile salts acids or alkali ?
Acids
What are the roles of bile salts in lipid digestion ?
- emulsify large fat droplets = increases SA for action of lipase
- transport via formation of mixed micelles = stabilises products of triglyceride hydrolysis
What do micelles contain ?
- bile salts
- monoglycerides
- fatty acids
- phospholipids
- cholesterol
What is the condition caused primarily by an absence/deficiency of bile salts ?
Steatorrhea (a fatty type of diarrhoea)
Currently, what are the proposed methods of lipid transport across membranes ?
simple diffusion
phospholipids in micelles bind to the phospholipid membrane and release contents into the cell
Free fatty acid transporters
FAT and CD36
Monoglyceride transporters
evidence for carrier-mediated mechanisms (no details)
What is the average dissociation constant (pKa) of free fatty acids ?
~ 4.9
means: at pH 4.9, 50% of fatty acids will be undissociated and susceptible to simple diffusion
Describe how lipids are turned into chylomicrons …
- bile salts emulsify + form micelles
- micelles diffuse into cells
- triglycerides reform within cell
- packaged into chylomicrons in endoplasmic reticulum
Where are chylomicrons transported to ?
Lymphatic system via lacteals
Where is cholesterol absorbed?
duodenum
Which protein is cholesterol absorption dependant on ?
NPC1L1 protein
Niemann-Pick C1-Like 1 protein
What does the NPC1L1 protein do in the intestine ?
enables receptor mediated endocytosis of cholesterol into the cells
Which receptor is the target of the drug Ezetimibe ?
NPC1L1 protein
What is the action of the drug Ezetimibe ?
Inhibits endocytosis of cholesterol into intestine = decreases plasma cholesterol
What drug can Ezetimibe be used in combo with/instead of ?
statins
usually in cases where the patient is allergic to statins
Name 3 short chain fatty acids …
- butyrate
- propionate
- acetate
Where do short chain fatty acids present in the GI tract come from ?
Bacterial fermentation of undigested polysaccharides in the colon
not really from the diet
What are short chain fatty acids mainly used for once absorbed ?
intracellular metabolism
don’t pass into the blood at all really
How are short chain fatty acids absorbed ?
by the SMCT1 protein = a Na-coupled transporter
driven by a Na-K pump on opposite membrane
Which short chain fatty acid is associated with a decreased risk of colon cancer and metabolic diseases (e.g diabetes) ?
butyrate
Which short chain fatty acids are associated with an increased risk of colon cancer and metabolic diseases (e.g diabetes) ?
proprionate
acetate
How is water absorbed into the small intestine ?
following an osmotic gradient
full explanation unknown…
- via junctional complexed between cells ?
- via SGLT1 and amino acid transporters ?
- NOT aquaporins
What creates the osmotic gradient across the intestinal epithelium ?
absorption of nutrients
water follows
What volume of water is absorbed per day, on average, by:
a) small intestine?
b) colon ?
8.4L total
a) small intestine = 6.5 L
b) colon = 1.9 L
Where is the majority of water absorbed in the GI tract?
small intestine following nutrient absorption
Roughly how much water is lost in faeces each day ?
100 ml
Which 2 ions come out in quite significant amounts in faeces ?
potassium (90mM)
bicarbonate (30mM)
Which steroid hormone regulates sodium channels in the distal colon?
aldosterone
= increases sodium absorption
What effect does aldosterone have on sodium absorption in the distal colon ?
INCREASES absorption
Is the transport/absorption of Na throughout the GI tract classed as active or passive transport ?
active
Is the transport/absorption of bicarbonate throughout the GI tract classed as active or passive transport ?
passive
Why do people with severe/chronic diarrhoea get hypokalaemia and metabolic acidosis ?
because a lot of potassium and bicarbonate are lost in faeces anyway, so excessive diarrhoea will expel excessive quantities of both ions resulting in hypokalaemia and metabolic acidosis
What causes diarrhoeas ?
increased osmotic load in the colon = increased fluid in faeces
What makes up the increased osmotic load in the colon of patients with diarrhoea ?
incomplete digestion and absorption of food
due to:
- lack of enzymes
- lack of transporters
- excess ion secretion into gut
- damage to mucosal cells
What can cause a person to have a lack of digestive enzymes or absorption transporters ?
**congenital problems **
- lactase deficiency
- glucose-galactose malabsorption (SGLT1 mutation)
disease of pancreas and biliary systems = steatorrhoea
- pancreatitis
- cystic fibrosis
- hepatitis
- gall stones
What can cause damage to the mucosa in the GI tract ?
immune/autoimmune diseases
- coeliac
- crohn’s
bacterial infections
= damage epithelium and decrease SA
What does dysentery mean ?
dysentery = an infection of the intestines that causes diarrhoea containing blood or mucus
What are the main infection causes of diarrhoea in the UK ?
Rotavirus
Norovirus
How does cholera and rotavirus cause diarrhoea ?
- virus produces a toxin
- toxin hijacks normal cellular processes
- intestine normal secretes 1L water a day
- in cholera secretion of water exceeds 20L a day
- toxins also may inhibit Na absorption (but not SGLT1)
What is oral rehydration therapy? How does it help in cases of cholera causing diarrhoea ?
oral rehydration therapy = drinking water with salt and glucose in it
helps because toxins from cholera inhibit Na absorption but not SGLT1 (glucose) absorption, so this increases glucose absorption, taking water with it
What are the 2 distinct groups of vitamins ?
- fat soluble
- water soluble
Name the fat soluble vitamins …
- Vitamin A
- Vitamin D
- Vitamin E
- Vitamin K
Name the water soluble vitamins …
- Vitamins in the B group
- Vitamin C
How are fat soluble vitamins absorbed ?
facilitated diffusion and/or endocytosis
What type of digestion/absorption also helps with absorption of fat soluble vitamins ?
requires optimal fat digestion
Patients with which diseases will be more likely to have fat-soluble vitamin deficiencies ?
- pancreatic disease
- biliary disease
How are water soluble vitamins absorbed ?
specific transporters (facilitated and secondary active)
B12 is via endocytosis
What are the 2 routes of Ca absorption ?
- transcellular = through the cell via transport proteins
- paracellular = through tight junctions between the cells
Which vitamin regulates the transcellular route of Ca absorption ?
Vitamin D
What is the name of the Ca channel protein in…
a) the small intestine ?
b) the kidney ?
small intestine = TRPV6
kidney = TRVP5
In the process of Ca absorption in the small intestine, which protein does Ca bind to within the epithelial cell?
Calbindin
Why does Ca bind to a protein within the epithelial cells ?
- removes excess Ca from cytoplasm because high levels of free Ca is detrimental to the health of the cell
- enables movement of Ca from apical to basolateral membrane
How is Ca removed from the intestinal epithelium in absorption ?
active transport via PMCA pump
- Ca out, H+ in
How does Vitamin D regulate Ca absorption ?
vitamin D binds to receptors that trigger transcription of 3 proteins:
- TRPV6 (Ca channel protein)
- Calbindin
- PMCA (Ca-H pump)
Where does iron absorption occur in the GI tract ?
duodenum
Is iron absorption a transcellular or paracellular process ?
transcellular
(travels through the cell, rather than between them)
Is iron absorption a transcellular or paracellular process?
transcellular
(travels through the cell, rather than between them)
What are the 2 mechanisms in which iron enters the apical membrane in the duodenum ?
- via DMT protein (co-transports Fe and H+)
- in the form of heme (not certain how)
In the process of iron absorption in the duodenum, what happens to heme once inside the cell ?
heme is oxidised, releasing iron in form of ferric ions
What form of iron is released from heme in the absorption of iron in the duodenum ?
ferric ions
What substance is reduced to form ferris ions ?
ferric ions —> ferrous ions
In the absorption of iron in the duodenum, what happens to the remaining heme protein once ferric ions have been released ?
It goes to form biliverdin, and therefore bilirubin
biliverdin is the precursor to bilirubin
What is the precursor of bilirubin?
biliverdin
In the absorption of iron in the duodenum, what happens to the ferrous ions within the cell ?
they are bound to a protein called mobilferrin, as they are toxic when left free
What is the ionic formulae for
a) ferric ions ?
b) ferrous ions ?
ferric ions = Fe3+
ferrous ions = Fe2+
What is the name of the protein that ferrous ions bind to once inside the intestinal epithelium ?
mobilferrin
How does iron leave the cell via the basolateral membrane ?
facilitated diffusion via FP1protein
What is the name of the iron transport protein on the basolateral membrane of the duodenal epithelial cells ?
FP1 protein
(ferroportin 1)
What is the iron plasma-transport protein called ?
plasma transferrin
Which hormone regulates iron absorption ?
Hepcidin
Where is hepcidin produced ?
by liver cells
Which transporter protein does hepcidin bind to in the regulation of iron absorption in the duodenum ?
FP1
ferroportin 1 on basolateral membrane
What causes a decrease in hepcidin production ?
iron deficiency
hepcidin is produced when the body has surplus iron in the blood
