8.6: Ions, vitamins & minerals Flashcards
Define diffusion
Net random movement of molecules from a region of high concentration to low concentration
Does diffusion occur more rapidly over microscopic distances in comparison to macroscopic distances?
Yes
What typically acts as a diffusion barrier in cells?
Cell membrane (enables cells to maintain cytoplasmic concentration of substances different from their extracellular concentrations)
Can water soluble (polar) molecules cross the diffusion barrier more easily than lipid soluble (non-polar) molecules?
No (Lipid soluble molecules can diffuse passively with minimal resistance in comparison to water soluble)
What word describes a region which has a relatively higher water potential to its surroundings?
Hypotonic
What 2 methods can molecules use to cross the epithelium to enter the bloodstream?
Paracellular transport through tight junctions and lateral intercellular spaces.
Transcellular transport through the epithelial cells.
What 3 methods can solutes
Simple diffusion
Facilitated diffusion
Active transport
What are the 2 types of transport proteins involved and describe how each work?
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 faster transport than carrier proteins).
3 types of carrier-mediated transport
Unilorters
Symporters - coupled transport
Antiporters - coupled transport
3 examples of uniporters
GLUT
VGCC
VGSC
Example of a symporter
Na+/glucose symporter (SGLT)
Example of an antiporter
Na+/H+ antiporter
What is the difference between primary and secondary active transport?
Primary active transport is linked directly to cellular metabolism whereas secondary active transport uses energy from the concentration gradient of another substance that is actively transported.
Give two examples of primary active transporters and where they’ve found
Na+/K+ ATPase (pancreatic HCO3- secretion)
H+/K+ ATPase (stomach - parietal cell)
Give examples of 3 secondary active transporters and where they’re found
SGLT-1 co-tranpsorter (Small bowel absorption of monosaccharides)
HCO3-/Cl- counter transport (Pancreatic HCO3- Secretion)
Na+/H+ counter transport (Pancreatic HCO3- Secretion)
Give examples of facilitated diffusion transporters and where they’re found
GLUT-2, GLUT-5 (Small bowel absorption of monosaccharides)
How are glucose and galactose absorbed?
Absorption of glucose and galactose is done by secondary AT (carrier proteins (SGLT-1) on enterocyte apical membrane, and electrochemical gradient)
SGLT-I has the ability to transport glucose against concentration gradient, therefore effective when extracellular luminal concentrations are comparatively less than that in enterocytes
How is fructose absorbed?
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.
How does glucose exit through the basolateral membrane and what carrier protein is involved?
Facilitated diffusion, carrier protein is GLUT-2 (high capacity, low affinity facilitative transporter).
In what part of the GI system is the greatest amount of water absorbed?
Small bowel (especially in the jejunum)
Approximately how many litres of water are absorbed in the small and large bowel daily?
Small bowel - 8L
Large bowl - 1.4L
Explain how the standing gradient osmosis is created.
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))
Explain how chloride ions are absorbed
Cl- co-transported with Na+ within ileum, exchanged with HCO3- (Colon) into enterocytes. Co-transporter executed through secondary active transport on apical membrane
What method do potassium ions use to be reabsorbed?
Passive transport - Diffusion
What parts of the GI tract absorb Ca2+
Duodenum and ileum
What stimulates absorption of Ca2+
Vitamin D (calcitriol) and parathyroid hormone
What does a Ca2+ deficient diet stimulate the release of?
PTH and calcitriol to enhance intestinal ability to absorb Ca2+
Outline the absorption of Ca2+ in enterocytes
Vitamin-D dependent uptake of Ca2+ across the apical membrane into the enterocyte is mediated by TRPV6 (IMcal). Cytoplasmic Ca2+ binding protein Calbindin-D permits the movement of Ca2+ from the apical membrane to the basolateral membrane. Calbindin proteins transport Ca2+ in cytosol, preventing action as intracellular signal.
Ca2+ extrusion from enterocytes performed by 2 proteins: PMCAI and NCXI (Na+/Ca2+ exchanger). 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.
NCXI exchanger against concentration gradient, low affinity, high capacity (requires larger concentrations).
Is Ca2+ normally more concentrated Extracellularly or intracellularly?
Extracellular > intracellular
What can Ca2+ be carried by across the apical membrane?
Intestinal calcium binding protein (IMcal) - facilitated diffusion
ion channel
What are the difference between the PMCA and Na+/Ca2+ exchanger?
PMCA has a higher affinity for Ca2+, but Na+/Ca2+ has a higher capacity than PMCA.
(Na+/Ca2+ requires larger concentrations of Ca2+ to be effective).
What does vitamin D deficiency cause?
Rickets - chidren
Osteomalacia - adults
How does 1,25-dihydroxy D3 taken up by enterocytes effect Ca2+ absorption?
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.
What are the implications for Ca2+ transport across the cell?
Need to transport Ca2+ while maintaining low intracellular concentrations
Binds to calbindin in cytosol, preventring its action as an intracellular signal
What processes in the body is iron important for?
Oxygen transport (RBCs)
Oxidative phosphorylation (mitochondrial transport chain)
(Iron exhibits properties such as an electron donor and acceptor)
Does the body have a mechanism for actively excreting iron?
No
How much iron does an adult ingest ~ and how much does the body absorb?
- Ingest 15-20 mg/dayAbsorb only 0.5-1.5 mg/day
What is iron present in the diet as?
- Inorganic iron (Fe3+ and Fe2+)
- Haem iron (Haemoglobin, myoglobin and cytochromes)
Which form of iron is easily absorbed?
Fe2+
What reduces Fe3+ to Fe2+?
Vit. C
How is dietary haem absorbed into enterocytes?
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.
What enzyme liberates Fe2+ from erythrocytes?
Haem oxygenase
Outline iron transport.
Fe2+ is oxidised by transmembrane copper-dependent feroxidase (Hephaestin) → Ferric (Fe3+) → Bound to apotransferrin → transferrin.
Fe2+ alternatively binds to cytoplasmic apoferritin forming ferritin micelle → globular protein complex (Fe2+ oxidised to Fe3+) → Crystallises within protein shell. Single ferritin = 4000 iron ions. Increased dietary ion absorption → Ferritin
Is ferritin available to be transported into plasma?
No
(Iron/ferritin is lost in the intestinal lumen and excreted in the faeces. Increase in iron concentration in cytosol increase ferritin synthesis.)
List the fat-soluble vitamins.
Vitamins A, D, E and K.
What is another name for vitamin B12, C and B1?
B12 - Cobalamin
C - Ascorbic acid
B1 - Thiamine
What organ contains a large store of vitamin B12?
Liver (2-5mg)
What is pernicious anaemia?
Impaired absorption of vitamin B12 which slows the maturation of red blood cells.
Outline vitamin B12 absorption.
HCL in stomach releases B12, which combines with haptocorrin. Cleaved by and bound to intrinsic factor (IF) (resistant to digestion) - synthesised in the gastric parietal cells; the B12-IF complex traverses into the SI whereby it binds to receptors in the ileum - complex is taken up by an enterocyte and bound to transcobalamin II - stored in liver or transported to tissues. Crosses the basolateral membrane from MDRI channels into capillaries.
In the stomach, what causes release of free vitamin B12?
Low pH and digestion of proteins by pepsin
However, B12 is easily denatured by HCL. How is this resolved?
Binds to R protein (haptocorrin) released in saliva from parietal cells, which survive in the stomach and are then digested in the duodenum.
What is intrinsic factor?
Vitamin B12 binding glycoprotein secreted by parietal cells. Vitamin B12/IF is resistant to digestion.
What does Vitamin B12/IF complex bind to in distal ileum?
Cubilin receptor
- List causes for VB12 deficiency.
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.
What happens to VB12 after it enters a cell and is therefore no longer bound to intrinsic factor?
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
