What are the 2 types of transporter proteins?
Carrier proteins and channel proteins (much faster)
What are the 2 types of ion channels?
Gated or non gated, pics
3 Types of carrier mediated transport
Uniport, symport, antiport NB: if both molecules are oppositely charged they are moved via symporters
Where does water absorption take place?
Most is reabsorbed - mainly in Jejunum, some in colon Needs power of ion absorption (mostly by diffusion)
Where does the water that you excrete come from?
Ingest (2L), saliva (1.2L), gastric secretions (2L), bile (0.7L), pancreas (1.2L), intestinal (2.4L) Small intestine absorbs (8L), colon (1.5L)
What is the standing gradient of osmosis driven by?
Driven by Na, and transport of Na from lumen into Enterocytes are complex and varies between species
How is sodium transported to keep the standing gradient of osmosis?
Counter-transport i exchange for H+ (proximal bowel), co-transport with a.a., monosaccharides (jejunum). co-transport with Cl- (ileum), restricted movement through ion channels (colon)
How do molecules cross the epithelium to enter the bloodstream?
Paracellular transport, transcellular transport
What type of gated can channel proteins be?
Voltage gated, ligand gated - extra/intracellular, mechanically gated
What is a uniport carrier?
Carries just on type of molecule across
What is an antiport/symport carrier?
Carries 2 molecules either in the same/opposite across the membrane
What are some examples for primary active transport?
Na/K ATPase, H/K ATPase
What are some examples for secondary active transport?
SGLT-1 co-transport, HCO3-/Cl- counter transport, Na/H counter transport
What are some examples for facillitated transport?
How is calcium absorbed in the intestines?
Cl- is co-transported with Na+ (ileum), exchanged with HCO3- (colon) into enterocytes - both secondary active transport
How is potassium absorbed in the intestines?
K+ diffuses in via paracellular pathways in small intestine, leaks out between cells in colon - passive transport
What happens to the intracellular sodium from the standing gradient osmosis?
Active transport of Na+ into lateral intercellular spaces by Na/K ATPase transport in the lateral plasma membrane
What happens when sodium is transported into the intercellular spaces?
Cl- and HCO3- are transported into the intercellular spaces as well and the high concentration of ions in the intercellular space causes the fluid to become hypertonic
What happens due to the fluid in the intercellular space becoming hypertonic?
Water distends in the intercellular channels and causes increased hydrostatic pressure, so ions and water move across the basement membrane of epithelium and are carried away by the capillaries
How is the standing gradient of osmosis maintained? (image)
Where calcium absorbed in the gut?
In the duodenum and ileum - if diet low in Ca, then gut's absorptive ability inceases
What stimulates calcium absorption?
Vitamin D and parathyroid hormone stimulate absorption
How much calcium is absorbed in a day?
Diet 1-6g/day, secretions 0.6g, absorb 0.7g
What are the intra/extracellular [Ca2+]?
Low intra, but can increase in during various cellular functions High extracellular fluid, (plasma around 2.2mM and luminal varying)
How does Ca2+ get carried across the apical membrane?
Intestinal Ca-binding protein (IMcal) - facilitated diffusion OR ion channel
What is the function of Ca2+?
Acts as an intracellular signalling molecule - so this proses a problem when needed to be transported across the membrane
How is calcium transported into the cytosol?
Binds to calbindin, which prevents the action of Ca as an intracellular signal
How do we get Ca out of the cell and into the blood stream?
Ca2+ is pumped out by PMCA against conc gradient OR Ca2+ pumped across basolateral membrane via Na/Ca exchanger
What is an advantage of PMCA?
It helps maintain basal levels of Ca inside the cell
What does PMCA stand for?
Plasma membrane Ca2+ ATPase
What is the difference between the PMCA and Na/Ca exchanger?
PMCA - has a high affinity for calcium, but low capacity, so needs low conc to be effective, but is slower Na/Ca exchanger - has a low affinity but high capacity, so needs higher conc to be effective, but is very fast
What is vitamin D used for?
Essential for normal Ca absorption Deficiency causes rickets and osteoporosis
What happens when 1,25-DHD3 is taken up by enterocytes?
Enhances the transport of Ca through cytosol, increases levels of calbindin, increases rates of extrusion across basolateral membrane by increasing the level of Ca ATPase in the membrane
What is the function of iron?
It can act as an electron donor and an electron acceptor - oxygen transport and oxidative phosphorylation
What happens when iron is in excess?
Iron is toxic, but there is no mechanism for actively excreting iron - so iron should be absorbed rapidly when required and absorption should also be limited
How is iron present in your diet?
Adults ingest 15-20mg/day and absorb 0.5-1.5mg/day Present as: inorganic iron or as part of haem group
What is the difference between Fe3+ and Fe2+ absorption?
Can't absorb Fe3+ as it forms insoluble salts with hydroxide, phosphate and HCO3-
Why do we need vitamin C?
It reduces Fe3+ to Fe2+, so it can be absorbed
Can haem be absorbed readily?
It is a smaller part of the diet but it is more readily absorbed - 20% of presented
What are haem molecules and how are they absorbed?
Dietary haem is highly bioavailable, absorbed intact into enterocyte by HCP-1 and via receptor mediated endocytosis, with Fe2+ liberated by haem oxygenase
What is HCP-1?
Haem Carrier Protein 1
How do we uptake inorganic iron?
Dcytb catalyses reduction of Fe3+ to Fe2+ in process of iron absorption in duodenum, Fe2+ is transported via DMT-1, a H+-coupled co-transporter, Fe2+ binds to unknown factors, carried to basolateral membrane and moves via ferroportin ion channel into blood
What happens after the ferroportin-Fe2+ moves into blood?
Hephaestin converts Fe2+ and Fe3+, so Fe3+ binds to aoptransferrin and travels in blood as transferrin
How is the uptake of iron regulated?
Hepcidin suppresses ferroportin function to decrease iron absorption
What is DMT-1?
Divalent metal transporter 1
What is Dcytb?
Duodenal cytochrome B
What is hephaestin?
Transmembrane copper-dependent ferroxidase
If Fe2+ doesn't get transported out of the cell, what happens? (Ferritin pathway)
Fe2+ binds to apoferritin in cytosol, forming ferritin micelle, where Fe2+ is oxidised to Fe3+, which crystalises within the protein shell
What is ferritin?
Globular protein complex - which can store up to 4000 iron ions
What happens to excess ferritins?
Irreversible binding of iron to ferritins in epithelial cells, so iron isn't available for transport into plasma, so it is lost in intestinal lumen and excreted in faeces
How is ferritin synthesis increased?
Increased concentration of iron in cytosol
What are vitamins?
Organic compounds that can't be manufactured by the body but are vital to metabolism
How are vitamins taken up?
Fat soluble vitamins (ADEK) are transported to brush border in micelles, and K is taken up by active transport Specific transport mechanisms for vit C, folic acid, vit B1 and B12
Where is vit B12 stored?
Liver contains a large store, most B12 in food is bound to proteins
What happens if there is impaired absorption of vit B12?
Retards the maturation of RBC, causing pernicious anaemia
How is the denaturation of vit B12 in the stomach avaoided?
B12 is released when proteins broken down, but becomes denatured in acidic pH of stomach - so binds to R protein released in saliva from parietal cells
What are R proteins?
A.K.A. Haptocorrin - digested in duodenum
What happens to B12 in the duodenum?
When R protein is digested, B12 binds to intrinsic factor, which is resistant to digestion
What does the Vit B12/IF complex do when it reaches the ileum?
Binds to cubilin receptor, taken up in distal ileum, where it is broken down in mitochondria
What are intrinsic factors?
Vit B12 binding glycoproteins secreted by parietal cells
What happens to B12 in the cell, after IF is broken down?
B12 binds to TCII where it crosses the basolateral membrane and travels to the liver, TCII receptors on cells allowing for uptake of complex, then proteolysis breaks down TCII inside the cell, then B12 can be stored in the liver
How is B12 taken up by the cells from intestine?