Ions, vitamins and minerals Flashcards

1
Q

What is meant by molar

A

Molar = one mole per litre

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2
Q

What are the different units

A
Millimolar 		(mM) 	10-3
Micromolar 	(µM) 		10-6
Nanomolar 	(nM) 		10-9 
Picomolar 		(pM) 		10-12 
Femtomolar 	(fM) 		10-15
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3
Q

What is diffusion

A

The process whereby atoms or molecules intermingle because of their random thermal motion.

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4
Q

Why have multicellular organisms evolved circulatory systems

A

Diffusion occurs rapidly over microscopic distances, but slowly over macroscopic distances.

Multicellular organisms evolve circulatory systems to bring individual cells within diffusion range.

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5
Q

Describe the selective permeability of cell membranes

A

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.

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6
Q

Generally, in which direction does water move

A

Hypotonic — Hypertonic

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7
Q

What is meant by paracellular transport

A

through tight junctions and lateral intercellular spaces.

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8
Q

What is meant by transcellular transport

A

through the epithelial cells.

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9
Q

What are the tight junctions like in the small intestine

A

Looser- to allow the movement of water

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10
Q

Describe the different types of membrane transport

A

Solutes can cross cell membranes by simple diffusion, facilitated transport or active transport. Two types of transport proteins involved.

1) Channel proteins form aqueous pores allowing specific solutes to pass across the membrane.
2) 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.
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11
Q

Describe the structure of ion channels

A

Hydrophobic exterior

Hydrophilic interior- with an ion-selective filter

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12
Q

How can ion channels be activated

A
voltage-gated
intra- or extracellular ligand
Mechanical force (pressure)
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13
Q

What are antiporters often used for

A

Equalising charge

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14
Q

Describe the key difference between primary and secondary active transport

A

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.

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15
Q

Describe facilitated diffusion

A

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.

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16
Q

Give some examples of each type of membrane transport

A
o Primary – 
§ E.G. Sodium Potassium ATPase. 
o Secondary – . 
§ E.G. Bicarbonate/Chloride counter-transport, SGLT-1. 
§ Facilitated transport –
§ E.G. GLUT-5, GLUT-2.
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17
Q

What is key to remember about the enterocytes

A

Remember, enterocytes absorb GLUCOSE & GALACTOSE via 2nd active transport (SGLT-1 and sodium) and FRUCTOSE by facilitated diffusion (GLUT-5) - APICAL. Exit of glucose then via facilitated diffusion (GLUT-2) - BASAL.
Can’t move fructose against conc gradient- but it tends to be at a low conc in cells anyway

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18
Q

Describe the absorption of glucose and galactose

A

Absorption of glucose & galactose is by 2o active transport (carrier protein & electrochemical gradient). Carrier protein = SGLT-1 on apical membrane.

SGLT1 can transport glucose uphill against its concentration gradient (so effective when glucose at levels in the lumen are below those in the enterocyte

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19
Q

How does glucose then enter the blood

A

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.

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20
Q

Summarise the absorption of water and electrolytes

A

99% of the H2O presented to the GI tract is absorbed.
The absorption of water is powered by the absorption of ions.
The greatest amount of water is absorbed in the small intestine, esp the jejunum.
Many ions slowly absorbed by passive diffusion.
(Calcium and iron are incompletely absorbed, and this absorption is regulated)

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21
Q

How much water do we drink and how much water is reabsorbed

A

Approximately 8 litres of water a day absorbed in the small intestine.

Approximately 1.4 litres of water a day absorbed in the large intestine.

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22
Q

Where is this 8 litres coming from?

A

§ This water comes from:
o Ingestion (2L) and saliva (1.2L).
o Gastric secretions (2L) and bile (0.7L).
o The pancreas (1.2L) and the intestine (2.4L).

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23
Q

Ultimately, how is water reabsorbed

A

Water is absorbed by a process called “Standing Gradient Osmosis” – This process is driven by SODIUM transport.

24
Q

Describe the different ways in which Na+ os taken into cells

A

Transport of Na+ from lumen into enterocyte- complex and varies between species. Becomes 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

25
Q

Describe the reabsorption of other ions

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.

26
Q

What happens to the intracellular sodium

A

Active transport of Na+ into the lateral intercellular spaces by Na+K+ATPase transport in the lateral plasma membrane

27
Q

What happens to the intracellular Cl- and HCO3-

A

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.

28
Q

What is the consequence of the basolateral fluid becoming hypertonic

A

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- hydrostatic pressure of water helps the solutes pass through the BM

29
Q

Summarise the absorption of calcium

A

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

30
Q

Compare the intracellular concentration of calcium with the blood concentration

A

Low intracellular [Ca2+] approx 100 nM (0.1µM)
(but can increase 10– to 100-fold during various cellular functions).
High extracellular fluid [Ca2+] approx 1-3mM.
(Plasma [Ca2+] approx 2.2-2.6mM)
(Luminal [Ca2+] varies inmM range)

31
Q

How can Ca2+ be transported across the apical membrane

A

Ca2+ carried across apical membrane by:

i) Intestinal calcium-binding protein 	(IMcal)- facilitated diffusion.
ii) Ion channel
32
Q

Given the importance of Ca2+ as an intracellular signal, how is it transported without setting off a signal

A

Need to transport Ca2+ while maintaining low intracellular concentrations.
Binds to calbindin in cytosol, preventing its action as an intracellular signal- makes it inactive

33
Q

How is Ca2+ pumped across the basolateral cell membrane

A

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.

34
Q

How else can Ca2+ be pumped across the basolateral cell membrane

A

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.

35
Q

Describe the importance of Vitamin D

A

Essential for normal Ca2+ absorption

Deficiency causes rickets, osteoporosis.

36
Q

Describe the action of Vitamin D3 on enterocytes

A

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.

37
Q

What is a key property of iron

A

Iron can act as an electron donor and an electron acceptor

38
Q

What processes in the body is iron critical for?

A

Oxygen transport (red blood cells)

Oxidative phosphorylation
mitochondrial transport chain

39
Q

What is key to remember about iron

A

Iron is toxic in excess, but the body has no mechanism for actively excreting iron.
Therefore we have to limit absorption to when it is needed

40
Q

How much iron do we typically absorb

A

Adult ingests approx 15-20mg/day

but absorbs only 0.5-1.5mg/day.

41
Q

How does iron present in the diet

A

Iron present in the diet as:
a) inorganic iron (Fe3+ ferric, Fe2+ ferrous)
b) as part of heme (haem) group
(haemoglobin, myoglobin and cytochromes).

42
Q

As we cannot absorb Fe3+, how do we absorb it

A

§ We CANNOT absorb Fe3+ directly (like we do Fe2+) so we absorb it via:
· Fe3+ + insoluble salt binding (e.g. hydroxide, phosphate, bicarbonate).
· Vitamin C reduction from Fe3+ to Fe2+.

43
Q

How else can we ingest iron

A

Heme smaller part of diet, but more readily absorbed (20% of presented, rather than 5%
We absorb this intact into the enterocyte via haem carrier protein 1 (HCP-1) which endocytoses via receptor mediated endocytosis. Fe2+ is then liberated by haem oxygenases. ).

44
Q

Describe dietary heme

A

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.

45
Q

Describe uptake of iron as Fe3+

A

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.

46
Q

How is iron then moved into the blood

A

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).

47
Q

How is iron excreted

A

OR:
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.
o The micelle is lost when the enterocytes are shunted off the tip of the villi.
o Increase of iron conc. in cytosol increases ferritin synthesis.

48
Q

Describe how we prevent too much iron absorption

A

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.

49
Q

What are vitamins

A

Organic compounds that cannot be manufactured by the body but vital to metabolism.

50
Q

Summarise the absorption of vitamins

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), vitamin B12

51
Q

Describe vitamin B12

A

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

52
Q

What happens in the stomach

A

In the stomach, low pH and the digestion of proteins by pepsin releases free vit B12. But B12 is easily denatured by HCl.

53
Q

How is the denaturation of B12 in the stomach avoided?

A

Binds to R protein (haptocorrin) released in saliva and from parietal cells.
R proteins digested in duodenum.

54
Q

Describe the role of intrinsic factor

A

o R proteins are then digested in the duodenum.
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).

55
Q

What happens to the B12 inside the cell

A

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.