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What are the two main routes by which molecules cross epithelium to enter the bloodstream?
How do channel proteins mediate facilitated diffusion?
How do carrier proteins mediate facilitated diffusion?
Name the three functional types of carrier-mediated transport described.
Give an example of a symport (cotransporter) mentioned in the text.
Which type of facilitated diffusion transport allows much faster transport: channels or carriers?
What distinguishes primary active transport from secondary active transport?
Name two examples of primary active transport and their associated locations/functions given in the text.
List the secondary active transport mechanisms mentioned and one associated function for each.
Which transporter mediates secondary active uptake of glucose and galactose in the intestine?
What capability of SGLT-1 makes it effective when luminal glucose is lower than enterocyte glucose?
How is fructose absorbed across the intestinal epithelium?
Which transporter mediates glucose exit at the basolateral membrane and what are its properties?
What drives water absorption in the gastrointestinal tract and how much is absorbed?
Are calcium and iron completely absorbed in the intestine?
What mechanism is described as 'standing gradient osmosis' driven by which ion?
Name four general types of membrane transport (image shown in answer).
How is Na+ actively transported from the enterocyte into the lateral intercellular spaces?
Which Na+ absorption mechanisms become more efficient along the intestine?
How is Na+ movement characterized in the colon?
How is Cl⁻ transported in the ileum relative to Na+ and HCO₃⁻?
What is the osmotic and hydrostatic consequence of water movement from the gut lumen into intercellular spaces?
Once ions and water enter intercellular spaces, how are they removed?
Describe K+ movement in the small intestine and colon.
Which intestinal regions absorb Ca²⁺?
Which hormones or factors stimulate intestinal calcium absorption?
What can cause hypercalcaemia related to parathyroid pathology?
How is Ca²⁺ carried across the apical membrane of enterocytes?
How is Ca²⁺ removed across the basolateral membrane of enterocytes by PMCA?
What is the role and characteristic of the Na⁺/Ca²⁺ exchanger at the basolateral membrane?
What is the tonicity of the intercellular spaces during intestinal ion transport?
What is the primary role of vitamin D in the intestine?
How does vitamin D3 increase intracellular calcium transport in enterocytes?
How does vitamin D3 increase basolateral extrusion of calcium from enterocytes?
Name two clinical consequences of vitamin D deficiency mentioned in the notes.
In which chemical forms is dietary iron present?
Why must Fe3+ be reduced before absorption and which vitamin helps this?
Which enzyme catalyses reduction of Fe3+ to Fe2+ in the duodenum?
Which transporter moves Fe2+ across the apical membrane of enterocytes?
After entering enterocytes, how does Fe2+ reach the blood across the basolateral membrane?
What is the role of hephaestin in iron transport?
How does iron travel in blood after basolateral export and oxidation?
How is iron stored inside enterocyte cytosol?
What is the storage capacity of a single ferritin molecule?
How does increased dietary iron affect ferritin and absorption?
What happens to iron irreversibly bound to ferritin in epithelial cells?
What effect does an increase in cytosolic iron concentration have on ferritin synthesis?
Besides iron regulation, what is another role of ferritin mentioned?
What is the consequence of impaired vitamin B12 absorption on red blood cells?
How is free vitamin B12 released in the stomach?
Why does vitamin B12 bind to R protein (haptocorrin) in the stomach?
Where are R proteins that bind vitamin B12 digested?
What is intrinsic factor (IF) and where is it secreted?
What property of the vitamin B12/intrinsic factor complex aids absorption?
What happens to vitamin B12 absorption if intrinsic factor is absent?
To which receptor and where in the intestine does the vitamin B12/IF complex bind for uptake?
What uptake mechanism is thought to mediate vitamin B12/IF internalization in the distal ileum?
Where is the vitamin B12/IF complex possibly broken after cellular uptake?
Which protein binds vitamin B12 after it leaves the enterocyte and facilitates transport across the basolateral membrane?
How does vitamin B12 travel to the liver in the circulation?
How do cells uptake vitamin B12 from the circulation when it is bound to TCII?
What happens to transcobalamin II (TCII) inside cells after uptake?
Flashcards in dit deck (63)
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What are the two main routes by which molecules cross epithelium to enter the bloodstream?
- Paracellular transport: through tight junctions and lateral intercellular spaces
- Transcellular transport: through the epithelial cells
transport epithelium -
How do channel proteins mediate facilitated diffusion?
Channel proteins form aqueous pores allowing specific solutes to pass across the membrane.
facilitated channels -
How do carrier proteins mediate facilitated diffusion?
Carrier proteins bind the solute and undergo a conformational change to transport it across the membrane.
facilitated carriers -
Name the three functional types of carrier-mediated transport described.
- Uniport
- Symport (cotransporter, 2 ions move in together)
- Antiport (1 ion moves in, 1 ion moves out)
carriers modes -
Give an example of a symport (cotransporter) mentioned in the text.
SGLT-1
sglt-1 symport -
Which type of facilitated diffusion transport allows much faster transport: channels or carriers?
Channel proteins allow much faster transport than carrier proteins.
facilitated rate -
What distinguishes primary active transport from secondary active transport?
Primary active transport uses ATP; secondary derives energy from the concentration gradient of another actively transported substance.
active types -
Name two examples of primary active transport and their associated locations/functions given in the text.
- Na+/K+ ATPase (Pancreatic HCO3 Secretion)
- H+/K+ ATPase (Stomach – Parietal Cell)
primary atpase -
List the secondary active transport mechanisms mentioned and one associated function for each.
- SGLT-1 co-transport: Small bowel absorption of monosaccharides
- HCO3/Cl counter transport: Pancreatic HCO3 Secretion
- Na*/H+ counter transport: Pancreatic HCO3 Secretion
secondary examples -
Which transporter mediates secondary active uptake of glucose and galactose in the intestine?
- SGLT-1 (secondary active transport via carrier protein & electrochemical gradient)
carbohydrates transport -
What capability of SGLT-1 makes it effective when luminal glucose is lower than enterocyte glucose?
- Can transport glucose uphill against its concentration gradient
sglt1 transport -
How is fructose absorbed across the intestinal epithelium?
- Facilitated diffusion via GLUT-5, effective at relatively low luminal fructose concentrations
fructose glut5 -
Which transporter mediates glucose exit at the basolateral membrane and what are its properties?
- GLUT-2: facilitated diffusion; high-capacity, low-affinity; equilibrates glucose between plasma and enterocyte
glut2 carbohydrates -
What drives water absorption in the gastrointestinal tract and how much is absorbed?
- Driven by absorption of ions; 99% of water in GI tract is absorbed
water absorption -
Are calcium and iron completely absorbed in the intestine?
- No — calcium and iron are incompletely absorbed
minerals absorption -
What mechanism is described as 'standing gradient osmosis' driven by which ion?
- Standing gradient osmosis is driven by Na+
osmosis na+ -
Name four general types of membrane transport (image shown in answer).
- Simple diffusion
- Channel-mediated diffusion
- Carrier-mediated diffusion
- Active transport
membrane transport image -
How is Na+ actively transported from the enterocyte into the lateral intercellular spaces?
- By Na⁺/K⁺ ATPase transport in the lateral plasma membrane
sodium transport -
Which Na+ absorption mechanisms become more efficient along the intestine?
- Counter-transport with H⁺ (proximal bowel)
- Co-transport with amino acids and monosaccharides (jejunum)
- Co-transport with Cl⁻ (ileum)
sodium regionalization -
How is Na+ movement characterized in the colon?
- Restricted movement through ion channels in the colon
colon sodium -
How is Cl⁻ transported in the ileum relative to Na+ and HCO₃⁻?
- Cl⁻ is co-transported with Na⁺ in the ileum and exchanges with HCO₃⁻ into enterocytes
chloride ileum -
What is the osmotic and hydrostatic consequence of water movement from the gut lumen into intercellular spaces?
- Osmotic flow of water into intercellular spaces distends channels and increases hydrostatic pressure
water osmotic -
Once ions and water enter intercellular spaces, how are they removed?
- They move across the basement membrane of the epithelium and are carried away by capillaries
fluid capillaries -
Describe K+ movement in the small intestine and colon.
- K⁺ diffuses in via paracellular pathways in small intestine and leaks out between cells in colon
potassium paracellular -
Which intestinal regions absorb Ca²⁺?
- Duodenum and ileum absorb Ca²⁺
calcium regions -
Which hormones or factors stimulate intestinal calcium absorption?
- Vitamin D and parathyroid hormone stimulate absorption
calcium hormones -
What can cause hypercalcaemia related to parathyroid pathology?
- Parathyroid adenoma and parathyroid cancer can cause hypercalcaemia
calcium pathology -
How is Ca²⁺ carried across the apical membrane of enterocytes?
- By intestinal calcium-binding protein and ion channels
calcium apical -
How is Ca²⁺ removed across the basolateral membrane of enterocytes by PMCA?
- Pumped by plasma membrane Ca²⁺ ATPase (PMCA) against gradient; high affinity, low capacity; maintains very low intracellular Ca²⁺
pmca calcium -
What is the role and characteristic of the Na⁺/Ca²⁺ exchanger at the basolateral membrane?
- Na⁺/Ca²⁺ exchanger pumps Ca²⁺ out against gradient; low affinity, high capacity and requires larger Ca²⁺ concentrations to be effective
naca calcium -
What is the tonicity of the intercellular spaces during intestinal ion transport?
- Intercellular spaces are hypertonic
intercellular tonicity -
What is the primary role of vitamin D in the intestine?
Enhances normal Ca²+ absorption by enterocytes
vitamind calcium absorption -
How does vitamin D3 increase intracellular calcium transport in enterocytes?
By increasing levels of calbindin, which enhances Ca²+ transport through the cytosol
vitamind calbindin calcium -
How does vitamin D3 increase basolateral extrusion of calcium from enterocytes?
By increasing the level of Ca²+ ATPase in the basolateral membrane
vitamind ca2+atpase calcium -
Name two clinical consequences of vitamin D deficiency mentioned in the notes.
- Rickets
- Osteoporosis
vitamind disease -
In which chemical forms is dietary iron present?
- Inorganic iron (Fe3+, Fe2+)
- Haem group
iron diet -
Why must Fe3+ be reduced before absorption and which vitamin helps this?
Because Fe3+ cannot be absorbed; vitamin C reduces Fe3+ to Fe2+
iron vitaminc reduction -
Which enzyme catalyses reduction of Fe3+ to Fe2+ in the duodenum?
Duodenal cytochrome B (Dcytb)
iron dcytb duodenum -
Which transporter moves Fe2+ across the apical membrane of enterocytes?
Divalent metal transporter 1 (DMT-1), a H+-coupled co-transporter
iron dmt1 transport -
After entering enterocytes, how does Fe2+ reach the blood across the basolateral membrane?
Fe2+ moves via the ferroportin ion channel across the basolateral membrane into blood
iron ferroportin basolateral -
What is the role of hephaestin in iron transport?
Hephaestin is a copper-dependent ferroxidase that converts Fe2+ to Fe3+ at the basolateral membrane
iron hephaestin ferroxidase -
How does iron travel in blood after basolateral export and oxidation?
Fe3+ binds to apotransferrin and travels in blood as transferrin
iron transferrin apotransferrin -
How is iron stored inside enterocyte cytosol?
Fe2+ binds to apoferritin to form ferritin; Fe2+ is oxidised to Fe3+ and crystallises inside the protein shell
ferritin iron storage -
What is the storage capacity of a single ferritin molecule?
A single ferritin molecule can store up to 4,000 iron ions
ferritin iron capacity -
How does increased dietary iron affect ferritin and absorption?
Excess dietary iron increases ferritin production in enterocytes, which prevents excessive iron absorption
iron regulation ferritin -
What happens to iron irreversibly bound to ferritin in epithelial cells?
Iron/ferritin is not available for plasma transport and is lost in the intestinal lumen and excreted in faeces
ferritin excretion iron -
What effect does an increase in cytosolic iron concentration have on ferritin synthesis?
An increase in cytosolic iron concentration increases ferritin synthesis.
iron ferritin -
Besides iron regulation, what is another role of ferritin mentioned?
Ferritin is also an acute inflammatory phase molecule.
ferritin inflammation -
What is the consequence of impaired vitamin B12 absorption on red blood cells?
Impaired vitamin B12 absorption retards red blood cell maturation and causes pernicious anaemia.
vitaminb12 anaemia -
How is free vitamin B12 released in the stomach?
Low pH and pepsin digestion of proteins in the stomach release free vitamin B12.
vitaminb12 stomach -
Why does vitamin B12 bind to R protein (haptocorrin) in the stomach?
Vitamin B12 binds to R protein to avoid denaturation by HCl.
vitaminb12 haptocorrin -
Where are R proteins that bind vitamin B12 digested?
R proteins are digested in the duodenum.
vitaminb12 duodenum -
What is intrinsic factor (IF) and where is it secreted?
Intrinsic factor is a vitamin B12 binding glycoprotein secreted by parietal cells.
intrinsicfactor parietal -
What property of the vitamin B12/intrinsic factor complex aids absorption?
The vitamin B12/IF complex is resistant to digestion.
intrinsicfactor vitaminb12 -
What happens to vitamin B12 absorption if intrinsic factor is absent?
Without intrinsic factor there is no absorption of vitamin B12.
intrinsicfactor absorption -
To which receptor and where in the intestine does the vitamin B12/IF complex bind for uptake?
The vitamin B12/IF complex binds to the cubilin receptor and is taken up in the distal ileum.
cubilin ileum -
What uptake mechanism is thought to mediate vitamin B12/IF internalization in the distal ileum?
Uptake is thought to involve receptor-mediated endocytosis.
endocytosis absorption -
Where is the vitamin B12/IF complex possibly broken after cellular uptake?
The vitamin B12/IF complex is possibly broken in mitochondria.
mitochondria vitaminb12 -
Which protein binds vitamin B12 after it leaves the enterocyte and facilitates transport across the basolateral membrane?
Vitamin B12 binds to transcobalamin II (TCII) which crosses the basolateral membrane by an unknown mechanism.
tcii transcobalamin -
How does vitamin B12 travel to the liver in the circulation?
Vitamin B12 travels to the liver bound to transcobalamin II (TCII).
liver tcii -
How do cells uptake vitamin B12 from the circulation when it is bound to TCII?
Cells uptake the TCII–vitamin B12 complex via TCII receptors on the cell surface.
tcii receptors -
What happens to transcobalamin II (TCII) inside cells after uptake?
Proteolysis breaks down TCII inside the cell.
tcii proteolysis
Overview
- Key processes by which ions, vitamins and minerals cross gut epithelium and enter blood.
- Focus on membrane transport mechanisms, major nutrient uptake (carbohydrates, water, Ca²⁺, Fe, B12), and regulation.
Membrane transport routes
- Paracellular transport: movement between cells through tight junctions and lateral intercellular spaces.
- Transcellular transport: movement through cells across apical and basolateral membranes.
Alt: Membrane transport types — diffusion, channel, carrier, active transport.
Facilitated diffusion vs carriers vs channels
- Channel proteins: form aqueous pores, allow rapid, specific ion flow (e.g., ion channels).
- Carrier proteins: bind solute and change conformation; slower but specific.
- Uniport: single solute moves one way.
- Symport (cotransport): two solutes move together (e.g., SGLT-1 transports glucose with \(Na^+\)).
- Antiport (exchange): one solute in, one out.
- Channels are typically much faster than carriers.
Active transport
- Primary active transport: uses ATP directly.
- Examples: \(Na^+/K^+\) ATPase, \(H^+/K^+\) ATPase.
- Secondary active transport: uses energy stored in an electrochemical gradient set up by primary transport.
- Examples: SGLT-1 (glucose/galactose uptake with \(Na^+\)), \(HCO_3^-/Cl^-\) exchange, \(Na^+/H^+\) exchange.
Absorption of carbohydrates
- Glucose & galactose: taken up apically by SGLT-1 (secondary active, \(Na^+\)-coupled), enabling uptake even when luminal levels are low.
- Fructose: enters enterocyte by facilitated diffusion via GLUT-5.
- Basolateral exit: glucose and fructose leave the cell via GLUT-2 (facilitated diffusion; high-capacity, low-affinity).
Water absorption & standing-gradient osmosis
- Water movement follows solute (mainly \(Na^+\)) absorption — solvent drag and osmotic gradients.
- Approximately 99% of water in the GI tract is absorbed.
- Active ion pumping into lateral intercellular spaces makes them hypertonic; water flows into these spaces (standing-gradient osmosis) and is carried into capillaries.
Sodium, chloride and potassium handling
- \(Na^+\) apical entry: multiple mechanisms along the gut — co-transport with sugars/amino acids (jejunum), exchange with \(H^+\) (proximal small bowel), co-transport with \(Cl^-\) (ileum), restricted passage via channels in colon.
- \(Na^+\) is actively pumped into lateral intercellular spaces by \(Na^+/K^+\) ATPase on basolateral membrane.
- \(Cl^-\): often co-transported with \(Na^+\) in ileum; exchanged for \(HCO_3^-\) into enterocytes.
- \(K^+\): mainly moves paracellularly in small intestine; in colon it can leak back into lumen between cells.
Calcium (\(Ca^{2+}\)) absorption
- Sites: mainly duodenum and ileum.
- Regulation: increased by vitamin D and parathyroid hormone (PTH); low dietary \(Ca^{2+}\) upregulates absorption.
- Mechanism (transcellular, regulated):
- Apical entry via \(Ca^{2+}\) channels and transport by intestinal calcium-binding protein (e.g., calbindin).
- Cytosolic buffering/transport by calbindin.
- Basolateral extrusion by plasma membrane Ca^{2+} ATPase (PMCA) — high affinity, low capacity — and by the \(Na^+/Ca^{2+}\) exchanger — low affinity, high capacity.
- Clinical: vitamin D deficiency → rickets/osteoporosis; hypercalcemia may indicate hyperparathyroidism.
Vitamin D effects on Ca²⁺ uptake
- Vitamin D (especially D3) increases intestinal \(Ca^{2+}\) absorption by:
- Upregulating calbindin (enhances cytosolic Ca^{2+} transport).
- Increasing basolateral \(Ca^{2+}\) ATPase levels (enhances extrusion).
Iron absorption (Fe)
- Dietary forms: inorganic iron as \(Fe^{3+}\) or \(Fe^{2+}\), and haem-bound iron.
- Reduction step: \(Fe^{3+}\) must be reduced to \(Fe^{2+}\); vitamin C and duodenal cytochrome B (Dcytb) help reduce \(Fe^{3+}\rightarrow Fe^{2+}\).
- Apical uptake: \(Fe^{2+}\) enters enterocyte via DMT1 (divalent metal transporter 1), an \(H^+\)-coupled co-transporter.
- Intracellular handling:
- Iron can be stored by binding to ferritin (oxidised to \(Fe^{3+}\) inside the protein shell); ferritin prevents excess free iron and its toxicity.
- Increased cytosolic iron upregulates ferritin synthesis (mucosal block reduces systemic absorption).
- Basolateral export: iron leaves enterocyte via ferroportin; hephaestin (a copper-dependent ferroxidase) oxidises \(Fe^{2+}\rightarrow Fe^{3+}\) so it can bind transferrin in plasma.
- Regulation & losses: iron bound to ferritin in epithelial cells is lost when cells slough into lumen — a key regulatory point; body lacks active iron excretion.
Ferritin
- Intracellular iron storage complex; stores up to ~4,000 iron atoms per molecule.
- Sequesters iron irreversibly at the mucosal level, limiting transfer to plasma.
- Also an acute-phase protein; levels rise in inflammation.
Vitamin B12 (cobalamin) absorption
- Stomach phase: dietary B12 released from protein by gastric acid/pepsin, but to prevent acid denaturation B12 first binds R-protein (haptocorrin) from saliva and gastric secretions.
- R-protein is degraded in duodenum, freeing B12.
- Intrinsic factor (IF): glycoprotein secreted by gastric parietal cells; forms a stable B12–IF complex that resists digestion.
- Ileal uptake: B12–IF binds the cubilin receptor in distal ileum and is internalised (receptor-mediated endocytosis).
- Post-uptake: B12 released intracellularly, binds transcobalamin II (TCII) for transport across basolateral membrane and delivery via blood to the liver and other tissues.
- Clinical: lack of IF (e.g., pernicious anaemia) → impaired B12 absorption → megaloblastic anaemia and neurologic signs.
High-yield clinical pointers
- SGLT-1: crucial for oral rehydration and glucose–sodium co-transport in small bowel.
- Vitamin D deficiency → poor \(Ca^{2+}\) absorption → rickets/osteoporosis.
- Iron absorption regulated at mucosal level (ferritin, ferroportin, hepcidin influence).
- Pernicious anaemia = absent IF → B12 malabsorption.
Quick reference: common transporters/proteins
- \(Na^+/K^+\) ATPase — basolateral, maintains \(Na^+\) gradient.
- SGLT-1 — apical \(Na^+\)-glucose cotransporter.
- GLUT-5 — fructose facilitator apically.
- GLUT-2 — basolateral glucose exit.
- DMT1 — apical \(Fe^{2+}\) importer.
- Ferroportin — basolateral iron exporter.
- PMCA and \(Na^+/Ca^{2+}\) exchanger — basolateral \(Ca^{2+}\) extrusion.
- Intrinsic factor / cubilin — B12 uptake pathway.