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Year 1 - BRS > 11.6 - Ions, Vitamins and Minerals > Flashcards

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
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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
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3
Q

Define osmosis.

A

Diffusion of water from hypotonic to hypertonic medium

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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
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5
Q

By which methods can solutes cross cell membranes?

A
  • simple diffusion
  • facilitated transport
  • active transport
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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
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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
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8
Q

What types of ion channel proteins are there?

A
  • voltage-gated
  • ligand-gated (extracellular ligand)
  • ligand-gated (intracellular ligand)
  • mechanically gated
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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
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10
Q

Give examples of primary active transporters.

A
  • Na+/K+ ATPase (pancreatic HCO3- secretion)
  • H+/K+ ATPase (stomach parietal cell)
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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)
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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
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13
Q

Give examples of facilitated diffusion transporters.

A

GLUT-5, GLUT-2 (small bowel absorption of monosaccharides)

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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)
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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
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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
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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

Year 1 - BRS (73 decks)

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