Ions, Vitamins and Minerals Flashcards
What is diffusion?
The process whereby atoms or molecules intermingle because of their random thermal motion
What does the cell membrane act as?
Diffusion barrier, enabling cells to maintain cytoplasmic concentrations of substances different from their extracellular concentrations
What can pass more easily across a cell membrane?
Lipid soluble (non-polar) molecules can cross more easily than water soluble (polar) molecules
What is paracellular transport?
through tight junctions and lateral intercellular spaces
What is trans-cellular transport?
Through the epithelial cells
How can solutes cross cell membranes?
- simple diffusion
- facilitated transport
- active transport
What are channel proteins?
form aqueous pores allowing specific solutes to pass across the membrane
What are carrier proteins?
Bind to the solute and undergo a conformational change to transport it across the membrane
Which proteins allow for faster transport?
Channel proteins
What are the different types of ion channels?
Voltage gates Ligand gated (extra-cellular ligand) Ligand gated (intracellular ligands) Mechanically gated
What are the types of carrier-mediated transport?
Uniport
Symport
Antiport
What is primary active transport?
is linked directly to cellular metabolism (uses ATP to power the transport)
What is secondary active transport?
derives energy from the concentration gradient of another substance that is actively transported
What is facilitated diffusion?
Enhances the rate a substance can flow down its concentration gradient. This tends to equilibrate the substance across the membrane and does not require energy
Give example of primary active transporter?
Na+/K+ ATPase
Give examples of secondary active transporters?
SLGT-1 co-transport
HC03-/Cl- counter transport
Na+/H+ counter transport
Give examples of facilitates transport?
GLUT-5
GLUT-2
(Small bowel absorption of monosaccharides)
How does absorption of glucose and galactose take place?
Secondary active transport (carrier protein & electrochemical gradient). Carrier protein = SGLT-1 on apical membrane
How does GLGT1 work?
SGLT1 can transport glucose uphill against its concentration gradient (so effective when glucose at levels in the lumen are below those in the enterocyte
How is fructose absorbed?
facilitated diffusion
Carrier protein = GLUT-5 on apical membrane
Effective at relatively low concentrations of fructose in the lumen as tissue and plasma levels are low
What percentage of the water presented to the GI tract is absorbed?
99%
What is the absorption of water powered by?
Absorption of ions
Where is the greatest amount of water absorbed?
Small intestine
esp. jejunum
How are many ions absorbed?
Passive diffusion
How much water is absorbed in the small bowel?
8 litres
How much water is absorbed in the large bowel?
1.4 litres
Where do we get 9L of water from?
Ingest 2L Saliva 1.2L Gastic secretions 2L Bile 0.7L Pancreas 1.2L Intestinal 2.4L
What is osmosis driven by?
Na+
Transport of Na+ from lumen into enterocyte- complex
How does Na+ transport become more efficient as you travel down the intestine?
Counter-transport in exchange for H+ (proximal bowel)
Co-transport with amino acids, monosaccharides (jejunum)
Co-transport with Cl- (ileum)
Restricted movement through ion channels (colon)
How is Cl- absorbed?
Cl- co-transported with Na+ (ileum), exchanged with HCO3- (colon) into enterocytes.
Secondary active transport
How is K+ absorbed?
K+ diffuses in via paracellular pathways in small intestine, leaks out between cells in colon.
Passive transport.
Why is the intracellular space said to be hypertonic?
High conc of ions in the intercellular spaces
What does the intracellular space being hypertonic lead to?
Osmotic flow of water from the gut lumen via adjacent cells, tight junctions into the intercellular space.
Water distends the intercellular channels and causes increased hydrostatic pressure.
Ions and water move across the basement membrane of the epithelium and are carried away by the capillaries.
What parts of the bowel absorb Ca2+?
Duodenum
Ileum
What does a Ca2+ deficient diet do?
increases gut’s ability to absorb
What stimulates calcium absorption?
Vit D
PTH
What are the pathways via which Ca2+ is absorbed?
Directly via inter-cellular channels
Indirectly via channels facilitating diffusion via the duodenum of the small bowel
What happens after calcium is transported into the enterocyte?
Ideal for it not to be free
Otherwise the significant charge would result in an action potential
So it binds to calbindin
Calbindin allows it to be transported via PMCA
Or via exchange with sodium
Why is vitamin D so important in calcium absorption?
Increase the paracellular absorption of calcium
Increases the transcription of the channels that allows for absorption of calcium and for calcium to move out of enterocyte into capillaries
What are the two ways by which calcium is carried across apical membrane?
Intestinal calcium-binding protein (IMcal)- facilitated diffusion.
Ion channel
What are the implications for Ca2+ transport across the cell?
Need to transport Ca2+ whilst maintaining low intracellular concentrations
Binds to calbindin in cytosol, preventing its action as an intracellular signal
How does PMCA work?
Ca2+ pumped across basolateral membrane by plasma membrane Ca2+ ATPase (PMCA) against concentration gradient.
PMCA has a high affinity for Ca2+ (but low capacity).
Maintains the very low concentrations of calcium normally observed within a cell.
How does the ion channel work in calcium absorption?
Ca2+ pumped across basolateral membrane by plasma membrane Na+/Ca2+ exchanger against concentration gradient.
The Na+/Ca2+ exchanger has a low affinity for Ca2+ but a high capacity. Requires larger concentrations of Ca2+ to be effective
What does Vit D deficiency cause?
Rickets and osteoporosis
What does 1,25-dihydroxy D3 taken up by enterocytes do?
Enhances the transport of Ca2+ through the cytosol
Increases the levels of calbindin
Increases rate of extrusion across basolateral membrane by increasing the level of Ca2+ ATPase in the membrane.
How is iron transported?
Presented as haem or non haem
Haem iron is directly absorbed via a haem transporter
Can enter blood as Fe2+ or stored as ferritin
What is the role of duodenal cytochrome B?
Non haem iron changes to Fe2+ as it is the only form we can absorb
What channel is Fe2+ from non-haem absorbed via?
DMT1
(Divalent metal transporter 1)
H+ coupled co-transporter
What channel crosses the basolateral membrane?
Ferroporitin
Transports Fe2+ across apical membrane
What happens after Fe2+ crosses the apical membrane?
Hepastin transform Fe2+ to Fe3+
So it can enter the bloodstream
Hephaestin: transmembrane copper-dependent ferroxidase
What happens when iron levels are sufficient?
Activation of hepcidin which acts negatively on ferroportin
Prevents iron excess
How much iron is ingested and absorbed?
Adult ingests approx 15-20mg/day
But absorbs only 0.5-1.5mg/day.
How does ferritin store iron?
Binds to apoferritin in cytosol to form ferritin micelle.
Ferritin is globular protein complex. Fe2+ is oxidised to Fe3+ which crystallises within protein shell.
A single ferritin molecule can store up to 4,000 iron ions.
In excess dietary iron absorption, produce more ferritin.
Why do we need to prevent excess iron absorption?
Toxic in excess
How do we loose excess iron?
Iron/Ferritin is lost in the intestinal lumen and excreted in the faeces
Where is there a large store of Vitamin B12?
Liver
2-5mg
What does impaired absorption of B12 cause?
Retards the maturation of red blood cells - pernicious anaemia
What is most B12 in food bound to?
Proteins
How is B-12 absorbed (steps in stomach)?
Dietary B12 is attached to dietary protein
Acid causes detachment in stomach
But B12 is easily denatured by HCl so it attaches itself to haptocorin (usually secreted in saliva)
What is the function of haptocorin?
Prevents acid to destroy B12 molecules
Allows safe passage to the duodenum
What happens when B12 enters the duodenum?
Detaches from haptocorin
Travels through small bowel
What happens when B12 enters the ileum?
B12 attaches itself to intrinsic factors secreted by stomach parietal cells
Vit B12/IF is resistant to digestion.
No IF then no absorption of vit B12
Vit B12/IF complex binds to cubilin receptor, taken up in distal ileum
What happens when B12 enters cells?
Vit B12/IF complex broken
B12 binds to protein transcobalamin II (TCII), crosses basolateral membrane by unknown mechanism
Travels to liver bound to TCII.
TCII receptors on cells allow them to uptake complex.
Proteolysis then breaks down TCII inside the cell
