Ions, vitamins and minerals Flashcards
How can molecules cross epithelium to enter the blood stream?
- paracellular transport through tight junctions and lateral intercellular spaces
- transcellular transport through epithelial cells
What are channel proteins?
Aqueous pores allowing specific solutes to pass across the membrane
What are carrier proteins?
Bind to solute and undergo a conformational change to transport it across the membrane
What transports faster? Channel or carrier proteins?
Channel
What is the difference between primary and secondary active transport?
Primary - linked directly to cellular metabolism and uses ATP to power transport
Secondary - derives energy from conc gradient of another substance that is actively transported
Example of primary active transporters?
Na+/K+ ATPase
H+/K+ ATPase
Example of secondary active transporters?
GLUT-1 cotransport
HCO3-/Cl- transport
Na+/H+ counter transport
Example of facillitated transport?
GLUT5. GLUT2
How are carbohydrates absorbed? - glucose and galactose
Glucose and galactose by secondary active transport, carrier protein SGLT-1 on apical membrane that carries glucose against conc gradient
What is the carrier protein for glucose and galactose absorption
SGLT1
What is the carrier protein for fructose? What type of transport does it use?
Facillitated diffusion
GLUT5
How does glucose exit the enterocyte at the brush broder?
Facillitated diffusion
GLUT-2 high capacity low affinity facilitative transporter
What are specific issues in alimentary absorption?
Water and ions
Calcium
Iron
Vitamins B12
Where is most of the water absorbed? How is absorption of water powered?
Small intestine - esp jejunum
Powered by absorption of ions that are absorbed slowly by passive diffusion
How much water is absorbed per day in small intestine?
8 litres
How much water is absorbed per day in large intestine?
1.4 litres
How is Na+ transported into the enterocyte from the lumen?
Counter transport in exchange for H+
Co-transport with aa, monosaccharides (jejunum)
Cotransport with Cl- (ileum)
Restricted movement through ion channels (colon)
How is Cl- absorbed into enterocytes?
Co-transported with Na+ (ileum) and exchanged with HCO2- (colon) into enterocytes. Both secondary active transport
How is K+ absorbed into enterocytes?
Diffuses in via paracellular pathways in small intestine, leaks out between cells and colon. Passive transport
What happens to sodium taken into cells?
Active transport of Na+ into lateral intracellular spaces by Na+/K+ ATPase transport in the lateral plasma membrane
How are Cl- and HCO3- transported into the intercellular spaces
due to electical potential created by Na+ transport
How does water enter the gut cells?
Osmotic flow from 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 epithelium and carried away by capillaries
What parts of the small intestine absorb Ca2+
Duodenum and Ileum
What stimulates Ca2+ absorption?
Vit D and parathyroid hormone
What does a Ca2+ deficient diet do?
Increases gut ability to absorb
What is the intracellular fluid [Ca2+]
approx 100nM - low
What is the extracellular fluid [Ca2+]
What conc in plasma or lumen
approx 1-3mM
Plasma [Ca2+] 2.2-2.6 mM
Luminal varies
How is Ca2+ carried across the apical membrane
- Intestinal calcium binding protein (IMcal- facillitated diffusion)
- Ion channel
What is Ca2+ used for in the body?
Intracellular signalling molecule
What happens to calcium in cytosol and what does that do?
Binds to calbindin which prevents its action as an intracellular signal
How is Ca2+ pumped across the basolateral membrane?
Ca2+ ATPase (PMCA) against conc gradient
Na+/Ca2+ exchanger against conc gradient
How does PMCA maintain low conc Ca2+ in cell
it has high affinity Ca2+ but low capactiy so maintains the very low conc of calcium normally observed in cell
How does the Na+/Ca2+ exchanger work transporting Ca2+?
Low affinity for Ca2+ but high capacity so requires larger conc of Ca2+ to be effective
What does a deficiency of Vit D do?
Cause rickets, osteoporosis
What is Vit D essential for?
Normal Ca2+ absorption
What does 1,25-dihydroxy D3 do when taken up by enterocytes?
Enhances transport of Ca2+ through cytosol
Increases levels of calbindin
Increases rate of extrusion across basolateral membrane by increasing level of Ca2+ ATPase in the membrane
What is iron used as in the body?
Electron donor and acceptor
What processes in the body are iron critical for?
Oxygen transport RBC Oxidative phosphorylation (mitochondria transport chain)
How much iron does an adult ingest and how much do they absorb?
Ingest 15-20mg/day
Absorb 0.5-1mg/day
What does ion present as in the diet?
Inorganic iron eg Fe3+ ferric, Fe2+ ferous
Part of heme/haem group in haemoglobin, myoglobin and cytochromes
Which form of inorganic iron can the body absorb?
only Fe2+, can’t absorb Fe3+
What reduces Fe3+ to Fe2+? What catalyses this reaction?
Vit C
Catalysed by duodenal cytochrome B (dcytb)
How much of heme/haem is absorbed?
20% of presented instead of 5% of rest of iron
How is heme/haem absorbed into enterocyte?
Heme carrier protein HCP-1 via receptor mediated endocytosis
How is Fe2+ liberated?
Heme oxygenase
How is Fe2+ transported into enterocyte?
Divalent metal transporter 1 (DMT-1) which is a H+ coupled co-transporter
How does Fe2+ move into blood across basolateral membrane?
Via ferroportin ion channel
What converts Fe2+ to Fe3+?
Transmembrane copper dependent ferroxidase
What does Fe3+ bind to? How does it travel in blood
Bind to apotransferrin
Travels in blood as transferrin
What is a major iron regulating protein? What does it do?
Hepcidin
Supresses ferroportin function to decrease iron absorption
How else can iron transport in the body? (hint: micelle)
Bind to apoferritin in cytosol to form ferritin micelle
What is ferritin?
Globular protein complex which oxidises Fe2+ to Fe3+ which crystallises within protein shell
What happens when too much iron absorbed?
Irreversible binding of iron to ferritin in epithelial cells
Iron/Ferritin not available for transport into plasma
Iron/Ferritin lost in intestinal lumen and extreted in faeces
Increase in iron conc in cytosol increases ferritin synthesis
What are vitamins?
Organic compounds that cannot be manufactured by the body but vital to metabolism
What is the predominant mechanism to take up vitamins in the body?
Passive diffusion
What are the fat soluble vitamins
A, D, E, K
How are the fat soluble vitamins taken up in the body?
Transported to brush border in micelles. K taken up by active transport
What vitamins need specific transport mechanisms?
Vit C (ascorbic acid)
Folic acid
Vit B1 (thiamine)
Vit B12
Where is a store of Vit B12 found? What happens if there is impaired absorption of Vit B12
Liver
Retards maturation of red blood cells - pernicious anaemia
How is denaturation of vit B12 avoided in the stomach by HCl?
Binds to R protein (haptocorrin) released in saliva and from parietal cells. R proteins are digested in duodenum
What is the intrinsic factor IF?
Glycoprotein that binds to VitB12, makes it resistant to digestion. No IF then no absorption of vit B12
What does the vitB12/IF complex do?
Binds to cubilin receptor, taken up in distal ileum - receptor mediated endocytosis
What happens to vitB12 once it is in the cel
The VitB12/IF complex broken down, possibly in mitochondria. B12 bind to protein transcobalamin II (TCII), crosses basolaterla membrane by unknown mechanism. Travels to liver bound to TCII, TCII receptor on cels allow them to uptake complex and proteolysis breaks down TCII inside cells
How much water enters gastrointestinal tract a day?
7.5L due to various secretions
How much of the H2O in the GI tract is absorbed?
99%
