Ions+minerals Flashcards
Millimolar
Micromolar
Nanomolar
Picomolar
Femtomolar
-Meaning?
(mM) 10-3
(µM) 10-6
(nM) 10-9
(pM) 10-12
(fM) 10-15
Diffusion def
The process whereby atoms or molecules intermingle because of their random thermal motion.
How does water move across -tonic solutions?
What are the 2 methods substances can cross epithelia to enter the bloodstream?
Paracellularly-Through tight junctions and intercellular spaces
Transcellularly-Through epithelial cells
What is required for a solute to cross a membrane and which type is faster?
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.
What can ion channels do to prevent unwanted ions crossing the channel?
They can close
What are the 4 types of transport control protein channels?
What is the difference between uniport, symport and antiport
What is the difference between primary and secondary active transport?
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.
Difference between facilitated transport and active transport
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.
Give some examples of primary active transport
Na+/K+ ATPase (Pancreatic HCO3- Secretion)
H+/K+ ATPase (Stomach – Parietal Cell)
Give some examples of secondary active transport
SGLT-1 co-transport (Small bowel absorption of monosaccharides)
HCO3-/Cl- counter transport (Pancreatic HCO3- Secretion)
Na+/H+ counter transport (Pancreatic HCO3- Secretion)
Give some examples of facilitated transport
GLUT-5, GLUT-2 (Small bowel absorption of monosaccharides)
What type of transport is the absorption of glucose and galactose and what is the transport protein used?
Secondary active transport (carrier protein & electrochemical gradient). Carrier protein = SGLT-1 on apical membrane.
What type of transport is the absorption of fructose and what is the transport protein used?
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.
What type of transport is the exit of glucose from the basolateral membrane of the enterocyte and what is the transport protein used?
Exit of glucose at the basolateral membrane is by facilitated diffusion.
Carrier protein = GLUT-2, a high-capacity, low-affinity facilitative transporter.
Roughly how much water per day is absorbed in the small and large bowel?
Small bowel ~ 8L
Large bowel ~ 1.4L
What are the sources of water that is absorbed?
Ingest 2L
Saliva 1.2L
Gastric secretions 2L
Bile 0.7L
Pancreas 1.2L
Intestinal 2.4L
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?
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
How is K+ absorped?
K+ diffuses in via paracellular pathways in small intestine, leaks out between cells in colon.
Passive transport
How is Cl- absorped?
Cl- is co-transported with Na+, which are exchanged with HCO3- (colon) into enterocytes.
Both secondary active transport
Outline how the flow of Na+ out of the bowel lumen causes water reabsorption?
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
What parts of the intestine absorb Ca2+,
what promotes absorption
and what amount of Ca2+ is absorbed and secreted daily?
Duodenum and ileum
Vit D, PTH, Low Ca2+ diet
Diet 1-6g/day, secretions 0.6g. Absorb 0.7g.
What are the 2 methods Ca2+ can enter the apical membrane of an enterocyte?
Intestinal calcium-binding protein (IMcal)- facilitated diffusion.
OR
Ion channel(TRPV6)
How do Ca2+ levels vary between intracellularly and extracellularly?
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 2.2-2.6mM)
(Luminal [Ca2+] varies inmM range)
What is the implication of Ca2+ in the cytosol and how is it overcome?
Ca2+ can act as a signalling molecule, so is bound to calbindin within the enterocyte to prevent it from acting as a signalling molecule
What are the 2 ways Ca2+ is transported across the basolateral membrane and how does this maintain a low Ca2+ level intracellularly?
Ca2+ pumped across basolateral membrane by plasma membrane Ca2+ ATPase (PMCA) against concentration gradient.
PMCA has a high affinity for Ca2+ (but low capacity)
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.
What is the major use of vitamin D and what diseases are produced from a vit D deficiency?
Essential for normal Ca2+ absorption
Deficiency causes rickets, osteoporosis.
How does 1,25-dihydroxy D3 increase Ca2+ transport in the cytosol and extrusion from the cell?
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).
What are the 2 major metabolic functions of iron?
How is iron present in the diet?
a) inorganic iron (Fe3+ ferric, Fe2+ ferrous)
b) as part of heme (haem) group (haemoglobin, myoglobin and cytochromes).
What vitamin reduced Fe3+ to Fe2+?
Vitamin C
What will you find Fe3+ with in insoluble salts?
hydroxide,
phosphate,
HCO3-
How do we know that heme is absorbed intact into the enterocyte and how is Fe2+ liberated in the enterocyte?
Evidence that this occurs via heme carrier protein 1 (HCP-1), and via receptor-mediated endocystosis.
Fe2+ liberated by Heme oxygenase.
How is Fe3+ reduced to Fe2+ before being absorbed into the enterocyte?
Duodenal cytochrome B (Dcytb)
How is Fe2+ transported into the enterocyte and out of the basolateral membrane?
Divalent metal transporter 1 (DMT-1)
Fe2+ binds to unknown factors, carried to basolateral membrane, moves via ferroportin ion channel into blood
How is Fe2+ converted back into Fe3+ in the blood?
Hephaestin is a transmembrane copper-dependent ferroxidase that converts Fe2+ to Fe3+.
What does Fe3+ bind to in the blood for transport?
Fe3+ binds to apotransferrin, travels in blood as transferrin
How does hepcidin decrease iron uptake?
Suppresses ferroportin function to decreases iron absorption
What occurs when there’s excess iron in the diet?
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.
What is produced when there’s excess iron in the diet?
Ferritin produced by increased hepcidin to reduce iron levels
Can iron bound to ferritin be used in the metabolism?
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.
How are fat-soluble vitamins(A,D,E,K) transported to the brush border?
In micelles
-K is taken up by active transport
Where can most B12 be found in the diet?
Bound to proteins
How much B12 is stored in the liver and what does impaired absorption of B12 lead to?
Liver contains a large store (2-5mg)
Impaired absorption of vit B12 retards the maturation of red blood cells - pernicious anaemia
How is B12 destroyed in the stomach and how can we get around this issue?
B12 is denatured easily by HCl
-Binds to R protein (haptocorrin) released in saliva and from parietal cells.
R proteins digested in duodenum.
What is the purpose of intrinsic factor in B12 absorption and where/how is B12/IF absorbed?
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).
What occurs to B12/IF when absorbed into the enterocyte and what does it then bind to?
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.
