11.6 - Ions, Vitamins and Minerals Flashcards
1
Q
What is the basic terminology used?
A
- molar - one mole per litre
- millimolar (mM) = 10^-3
- micromolar (uM) = 10^-6
- nanomolar (nM) = 10^-9
- picomolar (pM) = 10^-12
- femtomolar (fM) = 10^-15
2
Q
What is diffusion?
A
- the process whereby atoms/molecules intermingle because of their random thermal motion
- occurs rapidly over microscopic distances, but slowly over macroscopic distances
- multicellular organisms evolve circulatory systems to bring individual cells within diffusion range
- cell membrane acts as a diffusion barrier, enabling cells to maintain cytoplasmic concentrations of substances different from their extracellular concentrations
- lipid soluble (non-polar) molecules can cross more easily than water soluble (polar) molecules
3
Q
Define osmosis.
A
Diffusion of water from hypotonic to hypertonic medium
4
Q
How can molecules cross the epithelium to enter the bloodstream?
A
- paracellular transport - through tight junctions and lateral intercellular spaces
- transcellular transport - through the epithelial cells
5
Q
By which methods can solutes cross cell membranes?
A
- simple diffusion
- facilitated transport
- active transport
6
Q
What two types of transport proteins are involved?
A
- channel proteins - form aqueous membrane pores allowing specific solutes to pass across the membrane, allow much faster transport than carrier proteins
- carrier proteins - bind to the solute and undergo a conformational change to transport it across the membrane
7
Q
What types of carrier protein are there?
A
- uniport - one molecule transported
- symport - two molecules transported together (co-transport)
- antiport - one molecule transported in one direction, another molecule transported in opposite direction
- symport and antiport = coupled transport
8
Q
What types of ion channel proteins are there?
A
- voltage-gated
- ligand-gated (extracellular ligand)
- ligand-gated (intracellular ligand)
- mechanically gated
9
Q
What are the two types of active transport?
A
- primary active transport - linked directly to cellular metabolism (uses ATP to power the transport)
- secondary active transport - derives energy from the concentration gradient of another substance that is actively transported
10
Q
Give examples of primary active transporters.
A
- Na+/K+ ATPase (pancreatic HCO3- secretion)
- H+/K+ ATPase (stomach parietal cell)
11
Q
Give examples of secondary active transporters.
A
- SGLT-1 co-transport (small bowel absorption of monosaccharides)
- HCO3-/Cl- counter transport (pancreatic HCO3- secretion)
- Na+/H+ counter transport (pancreatic HCO3- secretion)
12
Q
What is facilitated transport?
A
- enhances the rate a substance can flow down its concentration gradient
- tends to equilibrate the substance down the membrane and does not require energy
13
Q
Give examples of facilitated diffusion transporters.
A
GLUT-5, GLUT-2 (small bowel absorption of monosaccharides)
14
Q
How are glucose and galactose absorbed at brush border?
A
- by secondary active transport (carrier protein and electrochemical gradient)
- carrier protein = SGLT-1 on apical membrane
- SGLT-1 can transport glucose uphill against its concentration gradient (effective when glucose at levels in lumen below that of enterocyte)
15
Q
How does glucose exit at the basolateral membrane?
A
- facilitated diffusion through GLUT-2 carrier protein - a high-capacity, low-affinity facilitative transporter
- glucose between plasma and tissue/enterocyte generally equilibrated
16
Q
How is fructose absorbed at the brush border?
A
- facilitated diffusion through GLUT-5 carrier protein on apical membrane
- effective at relatively low concentrations of fructose in the lumen as tissue and plasma levels are low
17
Q
Where are water and ions absorbed in GI tract?
A
- 99% of H2O presented to GI tract is absorbed
- water absorption is powered by ion absorption
- greatest amount of water is absorbed in small intestine, especially the jejunum
- many ions slowly absorbed by passive diffusion
- calcium and iron are incompletely absorbed and absorption is regulated
18
Q
How much water do the small and large bowels absorb?
A
- 8L of water a day in small bowel
- 1.4L of water a day in large bowel
19
Q
Where does the water in our GI tract come from?
A
- ingest 2L
- saliva 1.2L
- gastric secretions 2L
- bile 0.7L
- pancreas 1.2L
- intestinal 2.4L
20
Q
How is Na+ transported into enterocyte?
A
- counter-transport in exchange for H+ in proximal bowel
- co-transport with amino acids and monosaccharides in jejunum
- co-transport with Cl- in ileum
- restricted movement through ion channels in colon
21
Q
How are other ions absorbed? (Cl- and K+)
A
- Cl- co-transported with Na+ (ileum), exchanged with HCO3- (colon) into enterocytes –> both secondary active transport
- K+ diffuses in via paracellular pathways in small intestine, leaks out between cells in colon –> passive transport
22
Q
What is standing gradient osmosis and how does it lead to water absorption from GI tract?
A
- how water is absorbed normally in GI tract
- driven by Na+ –> transported from lumen into enterocyte (becomes more efficient as travel down intestine)
- this Na+ is actively transported into lateral intracellular spaces by Na+K+ATPase transport in lateral plasma membrane
- Cl- and HCO3- transported into intercellular spaces due to electrical potential created by Na+ transport
- high concentration of ions causes fluid there to be hypertonic
- osmotic flow of water from gut lumen via adjacent cells, tight junctions into intercellular space
- water distends the intercellular channels and causes increased hydrostatic pressure
- ions and water move across basement membrane of epithelium and are carried away by capillaries
23
Q
Where and how much Ca2+ is absorbed?
A
- duodenum and ileum absorb it
- Ca2+ deficient diet increases gut’s ability to absorb
- vitamin D and PTH stimulate absorption
- diet 1-6g/day, secretions 0.6g and absorb 0.7g
24
Q
How much Ca2+ do we have intracellularly vs extracellularly?
A
- low intracellular - [Ca2+] approximately 100nM (can increase 100x during various cell functions)
- high extracellular - [Ca2+] approximately 1-3mM:
- plasma [Ca2+] approximately 2.2.-2.6mM
- luminal [Ca2+] varies
25
Q
How is Ca2+ moved across apical membrane of enterocytes?
A
- intestinal calcium-binding protein (IMcal) - facilitated diffusion
- ion channel
26
Q
What happens to Ca2+ when it is taken into cell?
A
- Ca2+ acts as an intracellular signalling molecule and we need to maintain low intracellular [Ca2+]
- so Ca2+ binds to calbindin in cytosol, preventing its action as an intracellular signal
27
Q
How is Ca2+ moved across the basolateral membrane?
A
- plasma membrane Ca2+ ATPase (PMCA) against concentration gradient - PMCA has high affinity but low capacity for Ca2+, maintains very low concentrations of calcium normally observed within a cell
- Na+/Ca2+ exchanger against concentration gradient - low affinity but high capacity for Ca2+, requires larger concentrations of Ca2+ to be effective
28
Q
What does vitamin D3 do to enterocytes to help with Ca2+ transport?
A
- enhances Ca2+ transport through cytosol
- increases calbindin levels
- increases rate of extrusion across basolateral membrane by increasing level of PMCA in membrane
29
Q
What processes in the body is iron critical for?
A
- oxygen transport in RBCs
- oxidative phosphorylation in mitochondria ETC
- can act as an electron donor and acceptor
30
Q
How much iron do we absorb and in which form?
A
- adults ingest 15-20mg a day and only 0.5-1.5mg is absorbed
- iron present in diet as inorganic iron (ferrous Fe2+ and ferric Fe3+) and as part of haem group (Hb, myoglobin, cytochromes)
- cannot absorb Fe3+ only Fe2+
- Fe3+ forms insoluble salts with hydroxide, phosphate, HCO3-
- vitamin C reduces Fe3+ to Fe2+
- haem is smaller part of diet but more readily absorbed (20% of presented rather than 5%)
31
Q
How is haem absorbed?
A
- dietary heme is highly bioavailable
- absorbed intact into enterocyte via heme carrier protein 1 (HCP-1), and via receptor-mediated endocytosis
- Fe2+ is liberated by heme oxygenase
32
Q
How are Fe3+ and Fe2+ taken up by enterocytes?
A
- duodenal cytochrome B (Dcytb) catalyses reduction of Fe3+ to Fe2+ in the process of iron absorption in duodenum
- Fe2+ transported via divalent metal transporter 1 (DMT-1), a H+ coupled co-transporter
33
Q
How is Fe2+ moved into the blood?
A
- Fe2+ binds to unknown factors, carried to basolateral membrane, moves via ferroportin ion channel into blood
- hephaestin is a transmembrane copper-dependent ferroxidase that converts Fe2+ to Fe3+
- Fe3+ binds to apotransferrin, travels in blood as transferrin
- hepcidin suppresses ferroportin function to decrease iron absorption
34
Q
How is Fe2+ stored in cell?
A
- binds to apoferritin in cytosol to form ferritin micelle
- ferritin is globular protein complex
- Fe2+ oxidised to Fe3+ which crystallises within protein shell
- single ferritin molecule can store up to 4000 iron ions
- in excess dietary iron absorption, produce more ferritin - ferritin prevents absorption of too much iron that can be toxic
35
Q
What happens to these ferritin stores?
A
- irreversible binding of iron to ferritin in epithelial cells
- iron/ferritin not available to transport into plasma
- iron/ferritin is lost in intestinal lumen and excreted in faeces
- increase in iron concentration in cytosol increases ferritin synthesis
36
Q
What are vitamins?
A
Organic compounds that cannot be manufactured by the body but vital to metabolism
37
Q
How are different vitamins taken up by the body?
A
- passive diffusion predominant mechanism
- fat soluble vitamins (A, D, E, K) transported to brush border in micelles
- K taken up by active transport
- specific transport mechanisms for vitamin C (ascorbic acid), folic acid, vitamin B1 (thiamine) and vitamin B12
38
Q
How is vitamin B12 important and where is it found?
A
- liver contains a large store (2-5mg)
- impaired absorption of vitamin B12 retards the maturation of RBCs - pernicious anaemia
- most vitamin B12 in food is bound to proteins
39
Q
What happens to vitamin B12 when it reaches the stomach?
A
- low pH and digestion of proteins (that it is attached to) by pepsin releases free vitamin B12
- B12 then binds to R protein (haptocorrin) released in saliva and from parietal cells as B12 is easily denatured by HCl
40
Q
What happens to B12 in the duodenum?
A
- R proteins are digested
- intrinsic factor (vitB12 binding glycoprotein) which was made by parietal cells in stomach bind to vitB12 and this vitB12/IF complex is resistant to digestion
- the complex binds to cubilin receptor and is taken up in distal ileum (thought to involve receptor-mediated endocytosis)
41
Q
What happens when vitB12/IF complex is inside a cell?
A
- complex broken - possibly in mitochondria
- B12 binds to protein transcobalamin II (TCII), crosses basolateral membrane by unknown mechanism and travels to liver
- TCII receptors on liver cells allow them to uptake the complex
- proteolysis then breaks down TCII inside the cell
