Ions, Vitamins and Minerals Flashcards
What does molar mean?
One mole per litre
What is diffusion?
-Diffusion: The process whereby atoms or molecules intermingle because of their random thermal motion.
•Diffusion occurs rapidly over microscopic distances, but slowly over macroscopic distances.
•Multicellular organisms evolve circulatory systems to bring individual cells within diffusion range.
How does the cell membrane act?
- The 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.
How does water move in osmosis?
hypotonic to isotonic to hypertonic
How can molecules cross the epithelium to enter the bloodstream?
- Paracellular transport: through tight junctions and lateral intercellular spaces
- Trasncellular trasporti through the epithelial cells
How do solutes cross cell membrane?
- simple diffusion
- facilitated transport
- active transport
What are the two types of transport proteins involved?
- Channel proteins form aqueous pores allowing specific solutes to pass across the membrane.
- Carrier proteins bind to the solute and undergo a conformational change to transport it across the membrane.
- Channel proteins allow much faster transport than carrier proteins.
What happens in an ion
channel?
-Ions selective filter in aqueous pore
What are different types of gates?
- Voltage gated
- Ligand gated (extracellular gland)
- Ligand gated (intracellular ligand)
- Mechanical gated
What re the two types of active transport?
- Primary active transport is 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.
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
What is absorption of glucose and galactose by?
- by secondary active transport (carrier protein & electrochemical gradient)
- Carrier protein = SGLT-1 on apical membrane
What is SGLT1?
SGLT1 can transport glucose uphill against its concentration gradient (so effective when glucose at levels in the lumen are below those in the enterocyte)
What are types of carrier mediated transport?
- Uniport
- Coupled transport: - Symport
- Antiport (exchange)
What are examples of primary active transporters?
- Na+/K+ ATPase (pancreatic HCO3- secretion)
2. H+/K+ ATPase (Stomach- partietal cell)
What are example of secondary active transporters?
- SGLT-1 co-transporter (small bowel absorption of mono-saccharides)
- HCO3-/Cl- counter transport (Pancreatic HCO3- secretion)
- Na+/H+ counter transport (Pancreatic HCO3- secretion)
What are examples of facilitated diffusion?
- GLUT-5, GLUT-2 (small bowel absorption of monosaccharides)
How is fructose absorbed?
-Absorption of fructose is by 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.
How does glucose exit?
- Exit of glucose at the basolateral membrane is by facilitated diffusion.
- Carrier protein = GLUT-2, a high-capacity, low-affinity facilitative transporter.
- Glucose between plasma and tissue/enterocyte generally equilibrated.
Describe the absorption of water
- 99% of the H2O presented to the GI tract is absorbed.
* The absorption of water is powered by the absorption of ions.
Where is most water reabsorbed?
• The greatest amount of water is absorbed in the small intestine, esp the jejunum.
Describe are ions are absorbed?
•Many ions slowly absorbed by passive diffusion.
-Calcium and iron are incompletely absorbed, and this absorption is regulated
How much water is absorbed in the small bowel?
•Approximately 8 litres of water a day absorbed in the small bowel.
How much water is absorbed in the large bowel?
•Approximately 1.4 litres of water a day absorbed in the large bowel.
Where does the water come from?
- Ingest: 2L
- Saliva: 1.2L
- Gastric secretions: 2L
- Bile: 0.7L
- Pancreas: 1.2L
- Intestinal: 2.4L
How is the standing gradient osmosis made?
- Driven by Na+
* Transport of Na+ from lumen into enterocyte- complex and varies between species.
How does the standing gradient osmosis become more efficient as travel down 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.
- Both secondary active transport
How is K+ absorbed?
- K+ diffuses in via paracellular pathways in small intestine, leaks out between cells in colon.
- Passive transport.
What happens to the intracellular Sodium?
Active transport of Na+ into the lateral intercellular spaces by Na+K+ATPase transport in the lateral plasma membrane
What causes fluid to become hypertonic?
•Cl- and HCO3- transported into the intercellular spaces due to electrical potential created by the Na+ transport.
-High conc of ions in the intercellular spaces causes the fluid there to be hypertonic
How does water help?
- Water form lumen into this area
1. Osmotic flow of water from the gut lumen via adjacent cells, tight junctions into the intercellular space.
2. Water distends the intercellular channels and causes increased hydrostatic pressure.
3. Ions and water move across the basement membrane of the epithelium and are carried away by the capillaries.
How is calcium absorbed?
- Duodenum and Ileum absorb Ca2+
- Ca2+ deficient diet increases gut’s ability to absorb.
- Vit D and parathyroid hormone stimulate absorption.
- Diet 1-6g/day, secretions 0.6g. Absorb 0.7g.
How is calcium absorbed in lumen?
- Directly by intracellular channels
2. INCL
What happens to calcium once inside?
- With calcium in enterocyte, don’t want to be free as significant charge as could result in a action potential
- So instead binds to calbindin
- Calbindin allows for it to be transported across interaside the by the PMCA or via exchange with sodium and calbdidin facilitates that
What does vitamin D do?
-Allows paracellular absorption of calcium and increases the transcription of the channels from absorption the calcium to lumen and increase channels that allow calcium into capillaries and out of enterocytes
What is low intracellular calcium?
- Low intracellular [Ca2+] approx 100 nM (0.1µM)
* (but can increase 10 to 100-fold during various cellular functions).
What is high extracellular calcium?
- High extracellular fluid [Ca2+] approx 1-3mM.
- (Plasma [Ca2+] approx 2.2-2.6mM)
- (Luminal [Ca2+] varies inmM range)
How is Ca2+ carried across apical membrane?
i) Intestinal calcium-binding protein (IMcal)- facilitated diffusion
ii) Ion channel
What are the implications for transport of Ca2+ into the cell from the lumen?
Ca2+ acts as an intracellular signalling molecule
What are the implications for Ca2+ transport across the cell?
- Need to transport Ca2+ while maintaining low intracellular concentrations
- Binds to calbindin in cytosol, preventing its action as na intracellular signal
What happens to the calcium?
- 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.
What is the affinity fo the Na+/Ca2+ exchanger like?
-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
Why is vitamin D needed?
- Essential for normal Ca2+ absorption
* Deficiency causes rickets, osteoporosis
What does vitamin D3 do?
•1, 25-dihydroxy D3 taken up by enterocytes:
• 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
What can iron act as?
an electron donor and an electron acceptor
Is iron toxic?
Iron is toxic in excess, but the body has no mechanism for actively excreting iron
How much iron is ingested?
- Adult ingests approx 15-20mg/day
* But absorbs only 0.5-1.5mg/day.
How is iron present in the diet?
a) inorganic iron (Fe3+ ferric, Fe2+ ferrous)
b) as part of heme (haem) group
(haemoglobin, myoglobin and cytochromes).
What type of iron can we absorb?
Cannot absorb Fe3+, only Fe2+
How is Fe3+ found?
- Fe3+ insoluble salts with:
- hydroxide,
- phosphate,
- HCO3-
What does vitamin c and heme do?
- Vit C reduces Fe3+ to Fe2+
* Heme smaller part of diet, but more readily absorbed (20% of presented, rather than 5%).
Why is iron important?
- Oxygen transport (red blood cells)
- Oxidative phosphorylation (mitochondrial transport chain)
How is iron transported?
- Iron enters as heme iron or non-heme iron (as 3+)
- Heme iron is directly absorbed by a heme transporter, which within the erenthrocyte goes directly into Fe2+ or can be stored as ferritin (as don’t want iron overload) or in non heme iron, ferric sulphate has to change into ferrous Fe2+ (as can only sorb this) via duodenal cytochrome B and once in desired form can be absorbed via DMT1,
- It can be directly into feroportin (channel), crosses it into basolateral membrane or as stored as ferritn
- Stored ferrretin has limited capacity and once a lot of iron this is shed across via epithelial cells so no iron overload but those transported across apical membrane has to be changed into ferrous form via hepastin which can be attached to transferrin in plasma or blood supply to be delivered in body e.g. to liver to be stored
- Once in liver and enough iron levels this activates the hepsiden which acts negatively on feroprotin which engages the feroprotin which dis allows the iron excess (enough iron body tells not to absorb further - negative impact of hepsidin)
How is heme absorbed?
- Dietary heme is highly bioavailable.
- Heme is absorbed intact into the enterocyte.
- Evidence that this occurs via heme carrier protein 1 (HCP-1), and via receptor-mediated endocystosis.
- Fe2+ liberated by Heme oxygenase.
How is iron absorbed?
- Duodenal cytochrome B (Dcytb) catalyzes the reduction of Fe3+ to Fe2+ in the process of iron absorption in the duodenum of mammals.
- Fe2+ transported via divalent metal transporter 1 (DMT-1), a H+-coupled co-transporter.
- Fe2+ binds to unknown factors, carried to basolateral membrane, moves via ferroportin ion channel into blood.
What happens when iron is in?
- Fe2+ moves across baslolateral membrane via ferroportin.
- Hephaestin is a transmembrane copper-dependent ferroxidase that converts Fe2+ to Fe3+.
- Fe3+ binds to apotransferrin, travels in blood as transferrin.
- (Hepcidin, the major iron regulating protein, suppresses ferroportin function to decreases iron absorption).
What does ferritin bind to?
Binds to apoferritin in cytosol to form ferritin micelle
What is ferritin?
- 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
What is ferritin role?
•In excess dietary iron absorption, produce more ferritin.
•Irreversible binding of iron to ferritin in the epithelial cells.
•Iron/Ferritin is not available for transport into plasma.
•Iron/Ferritin is lost in the intestinal lumen and excreted in the faeces.
-Increase in iron concentration in the cytosol increases ferritin synthesis
How are vitamins transported?
- Organic compounds that cannot be manufactured by the body but vital to metabolism.
- 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), vitamin B12
Where is vitamin B12 found?
- Liver contains a large store (2-5mg).
- Impaired absorption of vit B12 retards the maturation of red blood cells - pernicious anaemia.
- Most Vit B12 in food is bound to proteins.
What is R protein?
- In the stomach, low pH and the digestion of proteins by pepsin releases free vit B12.
- But B12 is easily denatured by HCl.
What is the intrinsic factor?
- Vit B12 binding glycoprotein secreted by 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 (mechanism unknown, but thought to involve receptor-mediated endocytosis).
What happens to Vitamin B12 once in the cell?
- Once in cell, Vit B12/IF complex broken- possibly in mitchondria
- 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.
What happens to this ferritin stored in enterocytes?
prevents absorption of too much iron (toxic)
How is B12 absorbed?
- dietary B12 attached to dietary protein and ingested into stomach and is detached due to stomach acid
- In the stomach B12 attaches itself to Hepatacroin (usually secreted by saiva) which will not allow acid to destroy B12 molecules to allow it to safely get across duodenum and then detaches itself hepatcorin and b12 gives through small bowel and in terminal ileum B12 attachés itself to intrinsic factors
- These are secreted in stomach by parietal cells and go across small bowel the whole time and are only absorbed in terminal ileum where specific channels to absorb V B12 and intrinsic factor complex
- then go to enterocytes and then detach itself from intrinsic factors and cross over basolateral membrane via MDR1 channel which will go across the capillaries where enterocytes will have produced trasocalamine protein which Vit B12 attaches to where it is carried into rest of body
How is the denaturation of B12 in the stomach avoided?
- Binds to R protein (haptocorin) rebased in saliva and from parietal cells
- R proteins digested in duodenum
