ions vitamins and minerals

Question 1

• What 2 methods can molecules use to cross the epithelium to enter the bloodstream?

Answer 1

Paracellular transport through tight junctions and lateral intercellular spaces.

Transcellular transport through the epithelial cells.

Question 2

What types of carrier-mediated transport are there and give an example of each

Answer 2

• Uniporters (one solute through membrane)GLUT, VGCCs, VGSCs etc.
• Symporters (one solute one coupled ion moving in same direction)Na+/glucose symporter (SGLT)
• Antiporters (solute and coupled ion moving in different directions)Na+/H+ antiporter

Question 3

• What is the difference between primary and secondary active transport?

Answer 3

Primary active transport is linked directly to cellular metabolism (energy from hydrolysis ATP)

whereas secondary active transport uses energy from the concentration gradient of another substance that is actively transported

Question 4

• Give examples of primary active transporters and where they’re found

Answer 4

Na+/K+ ATPase (pancreatic HCO3- secretion)

H+/K+ ATPase (stomach - parietal cell)

Question 5

• Give examples of secondary active transporters and where they’re found

Answer 5

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

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

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

Question 6

• How is fructose absorbed?

- How does glucose exit through the basolateral membrane and what carrier protein is involved?

Answer 6

Via facilitated diffusion using the carrier protein GLUT-5 on the apical membrane. Effective at relatively low concentrations of fructose in the lumen as tissue and plasma levels are low.

Facilitated diffusion, carrier protein is GLUT-2 (high capacity, low affinity facilitative transporter).

Question 7

• In what part of the GI system is the greatest amount of water absorbed?
• Approximately how many litres of water are absorbed in the small and large bowel daily?

Answer 7

Small bowel (especially in the jejunum)

Small bowel - 8L 
Large bowl - 1.4L

Question 8

• Explain how the standing gradient osmosis is created.

Answer 8

Transport of Na+ from lumen into enterocyte. Counter-transport (antiporter) through H+ exchange within duodenum.

Co-transport (Symport) with AAs and monosaccharides (Jejunum) 

Co-transport with Cl- (ileum)

Restricted movement through ion channels (Colon) 

(Generation of an increased intracellular solute concentration gradient within cytoplasm facilitates the movement of H20 through osmosis (High → Low H2O water potential)

Question 9

• Explain how chloride ions are absorbed.

- What method do potassium ions use to be reabsorbed?

Answer 9

Cl- co-transported with Na+ within ileum, exchanged with HCO3- (Colon) into enterocytes. Co-transporter executed through secondary active transport on apical membrane.

Passive transport - Diffusion

Question 10

• What parts of the GI tract absorb Ca2+?
• What stimulates absorption of Ca2+?
• What does a Ca2+ deficient diet stimulate the release of?

Answer 10

Duodenum and ileum

Vitamin D (Calcitriol) and parathyroid hormone

PTH and calcitriol to enhance intestinal ability to absorb Ca2+.

Question 11

• Outline the absorption of Ca2+ in enterocytes.

Answer 11

Vitamin-D dependent uptake of Ca2+ through calcium binding protein TRPV6 (IMcal) into enterocyte (facil diffusion)

Cytoplasmic Ca2+ binding protein Calbindin D transport Ca2+ in cytosol, preventing action as intracellular signal.

Ca2+ pumped across basolateral membrane by plasma membrane Ca2+ ATPase (PMCA) against concentration gradient. PMCA exhibits high affinity for Ca2+ (low capacity) to maintain low intracellular concentrations.

Or, pumped out by NCXI exchanger against concentration gradient, low affinity, high capacity (requires larger concentrations of Ca2+)

Question 12

• What can Ca2+ be carried by across the apical membrane?

- What are the difference between the PMCA and Na+/Ca2+ exchanger?

Answer 12

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

PMCA has a higher affinity but low capacity for Ca2+, but Na+/Ca2+ has a higher capacity and lower affinity than PMCA. 

(Na+/Ca2+ requires larger concentrations of Ca2+ to be effective).

Question 13

• How does 1,25-dihydroxy D3 taken up by enterocytes effect Ca2+ absorption?

Answer 13

Enhances 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.

Question 14

• What are the implications for Ca2+ transport across the cell?

Answer 14

Need to transport Ca2+ while maintaining low intracellular concentrations

Binds to calbindin in cytosol, preventing its action as an intracellular signal

Question 15

• What processes in the body is iron important for?

Answer 15

Oxygen transport (RBCs)

Oxidative phosphorylation (mitochondrial transport chain) 

(Iron exhibits properties such as an electron donor and acceptor)

Question 16

• Outline iron absorption for haem iron

Answer 16

Haem (ferrous) iron absorbed into the apical membrane through haem transporter. transported through the basolateral membrane via ferroportin into circulation.

Question 17

outline the process of iron absorption for Ferrous and ferric iron

Answer 17

Ferric iron is reduced to ferrous iron by duodenal cytochrome B in duodenum

ferrous fe2+ iron transported via divalent metal transporter 1 (DMT-1), a H+ coupled co transporter

transported through basolateral membrane by ferroportin

fe2+ converted back to Fe3+ by hephaestin (a transmembrane copper dependant ferroxidase)

Fe3+ binds to apotransferrin, travels in blood as transferrin

Question 18

• How much iron does an adult ingest ~ and how much does the body absorb?
• What is iron present in the diet as?

Answer 18

Ingest 15-20 mg/day
Absorb only 0.5-1.5 mg/day

1. Inorganic iron (Fe3+ and Fe2+)
2. Haem iron (Haemoglobin, myoglobin and cytochromes)

Question 19

• Which form of iron is easily absorbed?

- What reduces Fe3+ to Fe2+?

Answer 19

Fe2+

Vitamin C (catalysed by duodenal cytochrome B)

Question 20

• How is dietary haem absorbed into enterocytes?

- What enzyme liberates Fe2+ from erythrocytes?

Answer 20

Through the apical duodenal membrane into the enterocyte
an action potentiated by activity of haem carrier protein I (HCP-I)
and through receptor-mediated endocytosis.

Haem oxygenase

Question 21

what does Fe3+ form insoluble salts with

what happens to iron instead of its absorption if too much of it

Answer 21

phosphate, bicarbonate, hydroxide

Fe2+ binds to apoferritin
Fe2+ is oxidised to Fe3+ which is crystallised in protein shell

Question 22

how many iron ions can a single ferritin molecule contain

when causes more ferritin to be produced

what happens to ferritin after its production

Answer 22

up to 4000 ions

increased iron concentration

lost in the intestinal lumen and is excreted in faeces

Question 23

what does hepcidin do

Answer 23

negative feedback
an increase in iron production stimulates its release
it suppresses ferroportin function to decrease iron absorption

Question 24

• List the fat-soluble vitamins.

- What is another name for vitamin B12, C and B1?

Answer 24

Vitamins A, D, E and K.

B12 - Cobalamin 
C - Ascorbic acid 
B1 - Thiamine

Question 25

• What organ contains a large store of vitamin B12?

- What is pernicious anaemia?

Answer 25

Liver (2-5mg)

Impaired absorption of vitamin B12 which slows the maturation of red blood cells.

Question 26

• Outline vitamin B12 absorption.

Answer 26

HCL in stomach releases B12, which combines with haptocorrin.

Cleaved by and bound to intrinsic factor (IF) - synthesised in the gastric parietal cells

the B12-IF complex binds to receptors in the ileum

complex is taken up by an enterocyte, broken down, and B12 crosses the basolateral membrane into capillaries from MDR1 transporters

it is then bound to transcobalamin II

TCII receptors on cells allow them to be uptaken and stored in liver or transported to tissues.

Question 27

• In the stomach, what causes release of free vitamin B12?

- However, B12 is easily denatured by HCL. How is this resolved?

Answer 27

Low pH and digestion of proteins by pepsin.

    Binds to R protein (haptocorrin) released in saliva from parietal cells, which survive in the stomach and are then digested in the duodenum.

Question 28

• What is intrinsic factor?

- What does Vitamin B12/IF complex bind to in distal ileum?

Answer 28

Vitamin B12 binding glycoprotein secreted by parietal cells. Vitamin B12/IF is resistant to digestion

Cubilin receptor

Question 29

• List causes for VB12 deficiency.

Answer 29

Inadequate intake of sources containing the compound (Veganism)

Inadequate secretion of IF: pernicious anaemia (an autoimmune disorder) - autoantibodies interfere. 

Lack of stomach acid (achlorhydria) - after partial gastrectomy surgery. 

Malabsorption - diseases in the ileum reduces B12 absorption.

Question 30

• What happens to VB12 after it enters a cell and is therefore no longer bound to intrinsic factor?

Answer 30

B12 binds to transcobalamin II (TCII), and they both then cross the basolateral membrane and travel to the liver.

TCII receptors on hepatocytes allow them to take up the Vitamin B12/ TCII complex.

Proteolysis then breaks down TCII inside the cell.