Ions, Vitamins and Minerals

Question 1

K+ absorption

Answer 1

Moves passively into small intestine lumen paracellularly

Tends to move out of large intestine passively= high K+ conc in faeces

Question 2

Osmosis

Solution changes from what to what?

Answer 2

Hypotonic → Isotonic→ Hypertonic

Question 3

Methods of molecules entering bloodstream?

Adaptations to allow this?

Answer 3

Paracellular
through tight junctions and lateral intercellular spaces.

Transcellular
through the epithelial cells.

Tight junctions go all the way round the cell
Some tight junctions= tighter than others
Fixes membrane bound proteins into boundaries to help localise them to parts of the membrane= carries out function better

Question 4

Types of transport proteins

Faster one?

Answer 4

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 = faster transport than carrier proteins which has to undergo conformational change.

Question 5

Types of ion channels

Examples?

Answer 5

Voltage gated
Ligand-gated (extracellular ligand) (e.g. hormone)
Ligand-gated (intracellular ligand) (e.g. secondary messengers bind+ open them)
Mechanically gated (e.g. increased pressure)

Question 6

Types of carrier-mediated transport

Functions?

Answer 6

Uniport
Symport
Antiport (Counter-Transport) (trying to balance charge)
Symport+ Antiport= coupled transport, used in secondary active transport

Question 7

Examples of Primary active transporters

Examples Secondary active transporters

Examples of Facilitated transport /facilitated diffusion transporters

Answer 7

Na+/K+ ATPase, H+/K+ ATPase

SGLT-1 co-transport, HCO3-/Cl- counter transport, Na+/H+ counter transport

GLUT-5, GLUT-2

Question 8

Absorption of water+ ions process
Draw diagram
(slide3, lecture 6)
Driven by?

Answer 8

Driven by Na+
1. Transport of Na+ from lumen into enterocyte
Becomes more efficient as travel down intestine:
2. Counter-transport in exchange for H+ (proximal bowel)
3. Co-transport with amino acids, monosaccharides (jejunum)
4. Co-transport with Cl- (ileum)
5. Movement through ion channels (colon)
6. Cl- co-transported with Na+ (ileum), exchanged with HCO3- (colon) into enterocytes. Both secondary active transport.
7. K+ diffuses in via paracellular pathways (between cells instead of across cells) in small intestine, leaks out between cells in colon. Passive transport.
8. Active transport of Na+ into the lateral intercellular spaces by Na+K+ATPase transport in the lateral plasma membrane
9. Cl- and HCO3- transported into the intercellular spaces due to electrical potential created by the Na+ transport.
10. High conc of ions in the intercellular spaces causes the fluid there to be HYPERTONIC
11. Osmotic flow of water from gut lumen via adjacent cells, tight junctions into the intercellular space.
12. Water distends the intercellular channels and causes increased hydrostatic pressure.
13. Ions and water move across basement membrane of the epithelium +carried away by the capillaries.

Question 9

% H2O presented to GI tract= absorbed?

Answer 9

99%

Question 10

Greatest amount of water absorbed where?

Answer 10

Jejenum

Question 11

Calcium absorption process?
Implications of conc. gradient?
Draw it (slide 2, lecture 6)

Answer 11

Low intracellular Ca2+ but high extracellular fluid concentrations= Passive transport (goes easily down conc. gradient)

1. Ca2+ carried across apical membrane by:
   i) Intestinal calcium-binding protein (IMcal) facilitated diffusion.
   ii) Ion channels (don’t need to know specifics)
2. Ca2+ acts as an intracellular signalling molecule- don’t want to kick off intracellular signalling pathways, Need to transport Ca2+ while maintaining low intracellular concentrations.
3. Binds to calbindin in cytosol, preventing its action as an intracellular signal. (But at high conc. on other side= need active transport)
4. Ca2+ pumped across basolateral membrane by plasma membrane Ca2+ ATPase (PMCA) against concentration gradient.
5. PMCA has a high affinity for Ca2+ so even low conc. Ca it is still effective (but low capacity)= Maintains the very low concentrations of calcium normally observed within a cell.
6. Ca2+ also pumped across basolateral membrane by plasma membrane Na+/Ca2+ exchanger against concentration gradient. (secondary active transport)
7. The Na+/Ca2+ exchanger has a low affinity for Ca2+ but a high capacity (opposite to ATPase). Requires larger concentrations of Ca2+ to be effective but high capacity= works quickly

Question 12

Ca2+ deficient diet=?

Answer 12

Increases gut’s ability to absorb.

Question 13

What stimulates Ca2+ absorption?

Answer 13

Vit D

Parathyroid hormone

Question 14

Vitamin D absorption process?
Effects?
Importance?

Answer 14

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.

Normal Ca2+ absorption

Deficiency= Rickets in children, Osteoporosis in adulta.

Question 15

Iron function?

Answer 15

Act as an electron donor and an electron acceptor

Question 16

Processes in the body is iron critical for?

Answer 16

Oxygen transport (red blood cells)
Oxidative phosphorylation
(mitochondrial transport chain-cytochromes)

Question 17

Problem with iron?

Answer 17

Iron is toxic in excess, but the body has no mechanism for actively excreting iron
Need to be able to absorb it quickly if needed (crucial role)
But need to be able to limit absorption

Question 18

Amount of iron absorbed/day?

Answer 18

0.5-1.5mg/ day

Question 19

How is iron in diet?

Answer 19

Inorganic iron  (Fe3+ ferric, Fe2+ ferrous) 
As part of heme (haem) group (haemoglobin, myoglobin and cytochromes)= smaller part of diet but more readily absorbed (20% compared to 5%)

Question 20

Iron absorption process?
Draw it (slide 1, lecture 6)

Answer 20

1. Cannot absorb Fe3+, only Fe2+
2. Heme absorbed intact into the enterocyte.
3. Occurs via heme carrier protein 1 (HCP-1), and via receptor-mediated endocystosis
4. Fe2+ liberated by Heme oxygenase.
5. At same time, duodenal cytochrome B (Dcytb) catalyzes the reduction of Fe3+ to Fe2+
6. Fe2+ transported via divalent (Ca2+ can also move by it) metal transporter 1 (DMT-1), a H+-coupled co-transporter (H+ exchanged for Fe2+)
7. Fe2+ binds to unknown factors, carried to basolateral membrane, moves via ferroportin ion channel into blood.
8. Fe2+ moves across baslolateral membrane via ferroportin.
9. Hephaestin is a transmembrane copper-dependent ferroxidase that converts Fe2+ to Fe3+.
10. Fe3+ binds to apotransferrin, travels in blood as transferrin.
    OR AFTER STEP 7,
11. binds to apoferritin in cytosol to form ferritin micelle.
12. Ferritin is globular protein complex. Fe2+ is oxidised to Fe3+ which crystallises within protein shell.

Question 21

Fe3+ insoluble salts with?

Answer 21

Hydroxide,
Phosphate,
HCO3-

Question 22

Why is Vitamin C helpful for iron absorption?

Answer 22

Reduces Fe3+ to Fe2+

Question 23

What decreases iron absorption?

Answer 23

Hepcidin, major iron regulating protein, suppresses ferroportin function to decreases iron absorption
Inhibition of ferroportin= Fe2+ can get into enterocyte but not into blood= can’t be absorbed

Question 24

How much iron ions can be stored by ferritin molecule?

Answer 24

Up to 4,000 iron ions

Question 25

Excess dietary absorption of iron?

Answer 25

Produce more ferritin

Question 26

What happens to ferritin stored in enterocytes?

What increases ferritin synthesis?

Answer 26

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 (even though enterocytes= broken down again, these parts aren’t absorbed)

Increase in iron concentration in the cytosol increases ferritin synthesis

Question 27

Mechanisms of vitamin transport?
Fat-soluble vitamins?
Water soluble?

Answer 27

Passive diffusion= predominant mechanism

Fat soluble vitamins (A, D, E, K) transported to brush border in micelles by bile salts. K taken up by active transport.

Water soluble- Specific transport mechanisms for vitamin C (ascorbic acid), folic acid, vitamin B1 (thiamine), vitamin B12

Question 28

Impaired absorption of B12?

Answer 28

Retards the maturation of red blood cells - pernicious anaemia.

Question 29

B12 absorption- process?
Draw it (slide 5, lecture 6)

Answer 29

1. B12 is easily denatured by HCl.
2. Binds to R protein (haptocorrin) released in saliva and from parietal cells- stops it being denatured by B12.
3. R proteins digested in duodenum.
4. Vit B12 binding glycoprotein secreted by parietal cells.
5. Vit B12/IF is resistant to digestion= No IF then no absorption of vit B12
6. Vit B12/IF complex binds to cubilin receptor, taken up in distal ileum (mechanism unknown, but thought to involve receptor-mediated endocytosis)
7. Vit B12/IF complex broken- possibly in mitchondria
8. B12 binds to protein transcobalamin II (TCII), crosses basolateral membrane by unknown mechanism
9. Travels to liver bound to TCII.
10. TCII receptors on cells allow them to uptake complex.
11. Proteolysis then breaks down TCII inside the cell.