Ions+minerals

Question 1

Millimolar
Micromolar
Nanomolar
Picomolar
Femtomolar
-Meaning?

Answer 1

(mM) 10-3
(µM) 10-6
(nM) 10-9
(pM) 10-12
(fM) 10-15

Question 2

Diffusion def

Answer 2

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

Question 3

How does water move across -tonic solutions?

Answer 3

Question 4

What are the 2 methods substances can cross epithelia to enter the bloodstream?

Answer 4

Paracellularly-Through tight junctions and intercellular spaces
Transcellularly-Through epithelial cells

Question 5

What is required for a solute to cross a membrane and which type is faster?

Answer 5

TRANSPORT PROTEINS

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.

Question 6

What can ion channels do to prevent unwanted ions crossing the channel?

Answer 6

They can close

Question 7

What are the 4 types of transport control protein channels?

Answer 7

Question 7

What is the difference between uniport, symport and antiport

Answer 7

Question 8

What is the difference between primary and secondary active transport?

Answer 8

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.

Question 9

Difference between facilitated transport and active transport

Answer 9

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.

Question 10

Give some examples of primary active transport

Answer 10

Na+/K+ ATPase (Pancreatic HCO3- Secretion)

H+/K+ ATPase (Stomach – Parietal Cell)

Question 11

Give some examples of secondary active transport

Answer 11

SGLT-1 co-transport (Small bowel absorption of monosaccharides)

HCO3-/Cl- counter transport (Pancreatic HCO3- Secretion)

Na+/H+ counter transport (Pancreatic HCO3- Secretion)

Question 12

Give some examples of facilitated transport

Answer 12

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

Question 13

What type of transport is the absorption of glucose and galactose and what is the transport protein used?

Answer 13

Secondary active transport (carrier protein & electrochemical gradient). Carrier protein = SGLT-1 on apical membrane.

Question 14

What type of transport is the absorption of fructose and what is the transport protein used?

Answer 14

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.

Question 15

What type of transport is the exit of glucose from the basolateral membrane of the enterocyte and what is the transport protein used?

Answer 15

Exit of glucose at the basolateral membrane is by facilitated diffusion.
Carrier protein = GLUT-2, a high-capacity, low-affinity facilitative transporter.

Question 16

Roughly how much water per day is absorbed in the small and large bowel?

Answer 16

Small bowel ~ 8L
Large bowel ~ 1.4L

Question 16

What are the sources of water that is absorbed?

Answer 16

Ingest 2L
Saliva 1.2L
Gastric secretions 2L
Bile 0.7L
Pancreas 1.2L
Intestinal 2.4L

Question 17

What is the largest driver for osmosis out of the intestines and how does its movement out of the lumen vary along the proximal bowel, jejunum, ileum and colon?

Answer 17

Na+ transport

Becomes more efficient as travel down intestine:

Counter-transport in exchange for H+ (duodenum)
Co-transport with amino acids, monosaccharides (jejunum)
Co-transport with Cl- (ileum)
Restricted movement through ion channels (colon)

HACI

Question 18

How is K+ absorped?

Answer 18

K+ diffuses in via paracellular pathways in small intestine, leaks out between cells in colon.
Passive transport

Question 18

How is Cl- absorped?

Answer 18

Cl- is co-transported with Na+, which are exchanged with HCO3- (colon) into enterocytes.
Both secondary active transport

Question 19

Outline how the flow of Na+ out of the bowel lumen causes water reabsorption?

Answer 19

Na+ moves out of the bowel through multiple mechanisms, causing Cl- and HCO3- to be drawn out aswell by the electrochemical gradient.

This causes the intercellular solution to become hypertonic, leading to water leaving the bowel lumen and entering the tissue, where it is then absorbed by the capillaries and moved away

Question 20

What parts of the intestine absorb Ca2+,
what promotes absorption
and what amount of Ca2+ is absorbed and secreted daily?

Answer 20

Duodenum and ileum

Vit D, PTH, Low Ca2+ diet

Diet 1-6g/day, secretions 0.6g. Absorb 0.7g.

Question 21

What are the 2 methods Ca2+ can enter the apical membrane of an enterocyte?

Answer 21

Intestinal calcium-binding protein (IMcal)- facilitated diffusion.
OR
Ion channel(TRPV6)

Question 22

How do Ca2+ levels vary between intracellularly and extracellularly?

Answer 22

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 2.2-2.6 mM) (Luminal [Ca2+] varies in mM range)

Question 23

What is the implication of Ca2+ in the cytosol and how is it overcome?

Answer 23

Ca2+ can act as a signalling molecule, so is bound to calbindin within the enterocyte to prevent it from acting as a signalling molecule

Question 24

What are the 2 ways Ca2+ is transported across the basolateral membrane and how does this maintain a low Ca2+ level intracellularly?

Answer 24

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. --- 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.

Question 25

What is the major use of vitamin D and what diseases are produced from a vit D deficiency?

Answer 25

Essential for normal Ca2+ absorption Deficiency causes rickets, osteoporosis.

Question 26

How does 1,25-dihydroxy D3 increase Ca2+ transport in the cytosol and extrusion from the cell?

Answer 26

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(PMCA)**.

Question 27

What are the 2 major metabolic functions of iron?

Answer 27

Question 28

How is iron present in the diet?

Answer 28

a) inorganic iron (Fe3+ ferric, Fe2+ ferrous) b) as part of heme (haem) group (haemoglobin, myoglobin and cytochromes).

Question 29

What vitamin reduced Fe3+ to Fe2+?

Answer 29

Vitamin C

Question 30

What will you find Fe3+ with in insoluble salts?

Answer 30

**hydroxide, phosphate, HCO3-**

Question 31

How do we know that heme is absorbed intact into the enterocyte *and* how is Fe2+ liberated in the enterocyte?

Answer 31

Evidence that this occurs via **heme carrier protein 1 (HCP-1)**, and via receptor-mediated endocystosis. Fe2+ liberated by **Heme oxygenase.**

Question 32

How is Fe3+ reduced to Fe2+ before being absorbed into the enterocyte?

Answer 32

Duodenal cytochrome B (Dcytb)

Question 33

How is Fe2+ transported into the enterocyte and out of the basolateral membrane?

Answer 33

**Divalent metal transporter 1 (DMT-1)** Fe2+ binds to unknown factors, carried to basolateral membrane, moves via **ferroportin ion channel** into blood

Question 34

How is Fe2+ converted back into Fe3+ in the blood?

Answer 34

**Hephaestin** is a transmembrane copper-dependent ferroxidase that converts Fe2+ to Fe3+.

Question 35

What does Fe3+ bind to in the blood for transport?

Answer 35

Fe3+ binds to apotransferrin, travels in blood as transferrin

Question 36

How does hepcidin decrease iron uptake?

Answer 36

Suppresses ferroportin function to decreases iron absorption

Question 37

What occurs when there's excess iron in the diet?

Answer 37

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.

Question 38

What is produced when there's excess iron in the diet?

Answer 38

Ferritin produced by increased hepcidin to reduce iron levels

Question 39

Can iron bound to ferritin be used in the metabolism?

Answer 39

**No-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.

Question 40

How are fat-soluble vitamins(A,D,E,K) transported to the brush border?

Answer 40

In micelles -K is taken up by active transport

Question 41

Where can most B12 be found in the diet?

Answer 41

Bound to proteins

Question 42

How much B12 is stored in the liver and what does impaired absorption of B12 lead to?

Answer 42

Liver contains a large store **(2-5mg)** Impaired absorption of vit B12 retards the maturation of red blood cells - **pernicious anaemia**

Question 43

How is B12 destroyed in the stomach and how can we get around this issue?

Answer 43

B12 is denatured easily by HCl -**Binds to R protein (haptocorrin)** released in saliva and from parietal cells. R proteins digested in duodenum.

Question 44

What is the purpose of intrinsic factor in B12 absorption and where/how is B12/IF absorbed?

Answer 44

Binding to B12 to allow for absorption -B12/IF complex is resistant to digestion **No IF=No B12 absorption** *Vit B12/IF complex binds to cubilin receptor*, taken up in distal ileum (mechanism unknown, but thought to involve *receptor-mediated endocytosis*).

Question 45

What occurs to B12/IF when absorbed into the enterocyte and what does it then bind to?

Answer 45

**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.