Ions, minerals and vitamins

Question 1

What are the 2 overarching ways in which molecules can cross epithelium to enter cells

Answer 1

Paracellular transport- via tight junctions and lateral intercellular spaces.

Transcellular transport - through epithelial cells

Question 2

Contrast channel and carrier proteins

Answer 2

Channel proteins - form aqueous pores allowing specific solutes to pass across the membrane. They have ion selective filter in aqueous pore

Carrier proteins - bind to solute and undergo a conformational change to transport it across the membrane

Channels proteins allow much faster transport than carrier proteins

Question 3

What are the different types of channel proteins

Answer 3

• Voltage gated
• ligand gated (extracellular ligand)
• Ligand gated (intracellular ligand)
• Mechanically gated

Question 4

What are the different types of carrier mediated transport

Answer 4

Uniport, symport and antiport

Question 5

What are the 2 types of active transport (energy required)

Answer 5

Primary- linked directly to cellular metabolism (ATP)

Secondary - derives energy from the concentration gradient of another substance that is actively transported

Question 6

Summarise all membrane transport

Answer 6

Question 7

Give examples of primary active transporters , secondary active transporters and facilitated transporters covered in the GI course

Answer 7

Primary active -

• Na+/K+ ATPase
• H+/K+ ATPase (parietal cell stomach)

SECONDARY active

• SGLT1 cotransport (small bowel absorption of monosaccharides)
• HCO3-/Cl- counter transport (Pancreatic HCO3- secretion)
• Na+/H+ counter transport (Pancreativ HCO3- secretion)

Facilitated Transport

• GLUT5, GLUT 2 (small bowel absorption of monosaccharides)

Question 8

How is glucose and galactose absorbed by enterocytes

Answer 8

Via secondary active transport

SGLT-1 on apical membrane ; transport glucose against it’s concentration gradient (especially when glucose in lumen is low) by using energy from Na absorption

Exit of glucose at basolateral membrane is by facilitated diffusion via GLUT 2 carrier protein

Question 9

Contrast the properties of GLUT 2 and GLUT 5

Answer 9

GLUT 2- high capacity, low affinity facilitative expansion transporter. Hence glucose between plasma and tissue is equilibrated

GLUT 5- high affinity, hence effective at relatively low concentrations of fructose in the lumen as the tissue and plasma levels are low

Question 10

How is fructose absorbed

Answer 10

GLUT 5 carrier protein at apical membrane

Then same as glucose in basolateral membrane

Question 11

What part of the small bowel absorbs Ca²⁺

What hormones stimulate absorption

Answer 11

Duodenum and ileum

Vit D and PTH

Question 12

What increases gut ability to absorb calcium

Answer 12

Ca2+ deficient diet

Question 13

What’’s the intake of Ca2+ in diet and how much is absorbed and secreted

Answer 13

Diet- 1-6g/day

secretions - 0.6g

Absorbe 0.7g

Question 14

Summarise calcium absorption. Draw

Answer 14

Ca2+ carried across apical membrane by:

• intestinal calcium-binding protein (iMcal) - facilitated diffusion
• ion channel

Ca2+ pumped across basolateral membrane by:

• PMCA
• Na+/Ca2+ exchanger

Question 15

Contrast PMCA and Na+/Ca2+ exchanger in terms of properties

Answer 15

PMCA - plasma membrane Ca2+ ATPase

Has high affinity for Ca2+ but low capacity. Hence maintains very low concentration of calcium normally observed within a cell

Na+/Ca2+ exchanger

Low affinity for Ca2+ but high capacity. Hence requires larger concentrations foR Ca2++ to be effective

Question 16

What is the intracellular [Ca²⁺] and extracellular. Comment on the diffference between the 2

Answer 16

Intracellular - 100nM; however can increase 10 to 100 fold during various cellular functions

Extracellular

• Plasma - 2,2-2.6mM
• Luminal varies in mM range

Ca2+ entering enterocyte from lumen can act as intracellular signalling molecules; hence it bind to calbindin

Question 17

What’s the effect of Calcitriol on enterocytes

Answer 17

• Enhances the transport of Ca2+ through cytosol
• increase levels of calbindin
• increase levels of PMCA; hence increasing rate of extrusion of C2+ across basolaterla membrane

Question 18

What is the property of iron and what processes in the body is iron critical for?

Answer 18

Can act as an electron donor and acceptor

Hence important for:

• Oxygen transport - haemoglobin
• Oxidative phosphorylation

Question 19

How much iron does an adult in gets each day and in what forms does the iron present

Answer 19

15-20mg/day ingested

But absorbs only 0.5-1.5mg/day

Iron present in diet as:

• inorganic (ferric Fe3+/ ferrous Fe2+)
• part of haem group (haemoglobin, myoglobin and cytochromes)

Question 20

What form of iron can we not absorb? Why is this the case

Answer 20

Fe3+

as it forms insoluble salts with hydroxide , phosphate or HC03- ions

Question 21

What type of iron is more readily absorbed than the others

Answer 21

Haem- 20% of presented is absorbed unlike 5% for other forms

Hence highly bioavailability

Question 22

What reduces Fe3+ to Fe2+ in the blood

Answer 22

Vit C

Question 23

What transporter transports haem into enterocyte and how is the Fe2+ liberated

Answer 23

Via HCP-1 (heme carrier protein 1) and via receptor mediated endocytosis

the Fe2+ is liberated by Heme oxygenase

Question 24

Summarise how iron can be absorbed

Answer 24

DMT-1 (divalent metal transporter 1)- this is a H+ coupled co-transporter

Hephaestin- a transmembrane copper dependent ferroixdase

Fe3+ binds to apotransferrin to make transferrin

Question 25

What decreases iron absorption and how?

Answer 25

Hepcidin- suppresses ferroportin functions

Question 26

Explain what happens to excess irons that isn't absorbed via basolateral membrane

Answer 26

Binds to apoferritin to make ferritin micelles Here Fe2+ is oxidised to fe3+ which crystallises within protein shell this process is irreversible and the iron in ferritin isn't available for transport into plasma single ferritin can store up to 4000 iron ions

Question 27

What happens to excess ferritin stored in entercytes.

Answer 27

Iron/ferritin lost in intesitnal lumen and excreted in feaces increase in iron concentration in cytosol increases ferritin synthesis

Question 28

What are Vitamins ? Give examples and how are they absorbed

Answer 28

Compounds vital for metabolism but cannot be manufactured by the body Vit A,D,E - passive diffusion Vit K- taken up by acitve transport specific transport mechanism for: * Vit C (ascorbic acid) * folic acid * Vit B1 * Vit B12

Question 29

Where is Vit B12 stored and what does impaired Vit B12 lead to? In food what is Vit B12 bound to?

Answer 29

Stored in liver (2-5mg) impaired B12 absorption slows down red cell maturation - pernicious anaemia most. Vit B12 in food is bound to proteins

Question 30

Summarise Vit B12 absorption

Answer 30

Vit B12 cleaved forum protein in stomach by HCl and pepsin binds to haptocorrin (made by parietal cells/salivary gland) in duodenum binds to **intrinsic factor -**very important for absorption as it's resistant to digestion Vit B12/IF bind to cubilin receptor in distal ileum to be absorbed via receptor mediated endocytosis Vit B12/iF broken in mitochondria and then binds to transcobalamin II (TCII) and enters blood where it travels to liver TCII receptors on liver allows uptake TCII broken down in Hepatocyte

Question 31

How much water does the small bowel and colon absorb

Answer 31

Small intestine - 8L- most occur in jejunum as it has villae AND PLICAE circulares colon- 1.4L N.B. 99% of water in GI is absorbed

Question 32

We ingest about 2L of water a day, where does the other amount of water come from (that get absorbs)

Answer 32

Question 33

Descirbe the mechanism of standing gradient osmosis, that causes absorption of water

Answer 33

Driven by Na+; enters enterocytes via different ways Then Cl- (that was co transported with Na in Ileum) is exchanged with HCO3- enters via secondary active transport K+ diffuses **passively** via paracellular pathways and leaks out between cells then Cl- and HCO3- transported into intracellular space using electric potential created by Na+ (via Na+/K+ ATPase in lateral plasma membrane) this makes intracellular space hypertonic, water enters from gut lumen via adjacent cells Water distends the intracellular channels to create a high hydrostatic pressure This forces ions and water across basement membrane of epithelium into capillaries

Question 34

In standing gradient osmosis , what are the different ways Na+ is transported into enterocytes as you travel down intestine

Answer 34

* Proximal bowel- Counter transport in exchange for H+ * jejunum - Co-transport with amino acids or monosaccharides * ileum- co-transport with Cl- * colon- restricted movement through ion channels N.b these processes differ at different point across different species and become more efficient as you travel the pathway