Digestion of polysaccharides + absorption of glucose Flashcards
Describe generally how glucose is distributed in the body after absorption
Glucose enters bloodstream -> GSIS -> Beta cells of pancreas secrete insulin.
Glucose (through hepatic portal vein) gets to liver.
Insulin signals for
Glucose -> Glycogen
AA -> Protein, NH3 (Urea cycle)
Glucose -> Lipids (VLDL)
Glucose enters muscles cells, brain cells, WAT cells
de Novo biosynthesis of glycogen:
Glycogen structure, weight and functions in different tissues?
Structure:
- Cytosolic granules of glycogen in cells
- Granules comprised of polysaccharides called glycogen (glucose monomers linked by a1,4-glycosidic bonds).
-Glycogenin head at reducing end acts as catalyst for production of new glycogen
-Non-reducing ends is where new glucose monomers attach -Branching points formed of a1,6-glycosidic bonds.
Weight:
1-2% of mass in msc
10% of mass in liver
Functions:
liver: glucose reservoir during fasting or exercise to maintain blood glucose levels
msc: fuels glycolysis during vigorous activity
What is catabolism? Name different reactions
How is the Kreb’s cycle central is anabolism?
Def: breaking bonds to extract electrons and ultimately yield ATP (through ETC with electron carriers)
Ex: glycolysis, fatty acid oxidation, protein degradation
Krebs:
Acetyl-Coa -> Lipogenesis, cholesterolgenesis
Nucleotides -> DNA, RNA
Heme, Fe-S clusters, Urea cycle, hormones
AA -> Protein biosynthesis
Oxaloacetate -> gluconeogenesis (PEP)
Describe digestion of polysaccharides and oligosaccharides (from starch -> glucose, location, enzymes, hydrolysis (Steps))
In mouth:
Starch (formed of amylopectin & amylose) -> Maltose (by salivary amylase, hydrolysis)
In small intestine:
Maltose -> glucose (by maltase, Hydrolysis)
Starch (amylopectin & amylose) -> oligosaccharides -> maltose -> glucose (by pancreatic amylase and maltase. hydrolysis)
Hydrolysis: breaking molecular bonds in reaction with water (activates water by breaking it)
2 steps
1: Active site in acidic AA (Asp or Glu) catalyzes transfer of part of amylose chain (glucose monomer) to enzyme (glycosylation of the active site) and releases starch.
2*: Second active site AA activates water (breaks water molecule) to break the bond between the enzyme and shortened amylose (deglycosylation).
*is this a second amylase enzyme?
Describe absorption of glucose.
What is the portal and hepatic vein?
What fuel do enterocytes rely on?
Monosaccharides are absorbed through the apical membrane of intestinal microvilli, through the basolateral membrane and into the portal bloodstream.
Portal vein: collects bloodstream from stomach, small intestine, spleen, colon and pancreas, directing to the liver.
Hepatic vein: vein from liver towards the heart.
*Enterocytes: rely on AA and SCFA for fuel, not glucose.
q
Why do cells need membrane transporters?
Describe the 3 types of membrane transporters + their subtypes and how they are regulated
How does glucose cross membranes and why does it use the specific mechanism in question?
Cells need membrane transporters because only certain small, nonpolar or lipophilic solutes can freely diffuse across the membrane.
They must use passive diffusion (channels or transporters, meaning no use of ATP) or active diffusion (use of ATP, such as with pumps).
- Channels: move solutes quickly, tightly regulated (typically gated)
2 types: voltage-gated (membrane potential) and chemical-gated (regulated by molecule and its availability). - Transporters: move solutes slower than channels but faster than pumps. Regulated by covalent modification
can be either a uniporter (moving an ion from high to low concentration) or a secondary energy transporter (moving one molecule agaisnt concentration gradient by tapping into the energy produced from another molecule’s transport.
2 types of secondary energy transporters: symporter (moving 2 molecules in the same direction) or antiporter (moving 2 molecules in opposing directions) - ATP-powered pumps: move solutes slowest of all the membrane transporters.Regulated by ATP availability
move a solute agaisnt its concentration gradient at the expense of ATP, expending its Gibb’s free energy storage (can transport one or several solutes, can be considered an antiporter or symporter)
Glucose crosses membranes using glucose transporters, because it is a large, uncharged polar molecule that cannot simply diffuse across the membrane.
Uses GLUT.
Firstly, what is lysine and why can’t it use simple diffusion to cross the membrane?
Explain how membrane transporters work together to facilitate uptake of nutrients (specifically, uptake of lysine)
Explain with the following example:
Na+/K+ ATPase, K+ channels and Na+/Lysine symporter
Lysine: crucial AA for metabolism, protein building block and carnitine biosynthesis in the liver (cannot use simple diffusion because uncharged), and for which movement across the membrane is energetically unfavourable (higher lysine concentration inside the cell than outside)
Step 1: establish Na+ gradient (normal membrane potential of -70mV) for function of Na+/lysine symporter, with Na+/K+ pump (3Na+ out for 2K+ in)
Step 2: High Na+ concentration in extracellular region drives lysine uptake by Na+/Lysine symporter (inports Na+ and Lysine inside cell against concentration gradient of lysine and with concentration gradient on Na+). The symporter destabilizes Na+ concentration gradient and thus destabilizes the membrane potential, which can inhibit proper function of the symporter.
Step 3: K+ channels maintain electrical chemical gradient (adequate membrane potential of -70mV) for function of Na+/K+ ATPase pump (by exporting K+).
Describe how the stomach is acidified. Draw it out.
Key words: Cl- channel, K+ channel, H+/K+ pump, HCO3/Cl-, apical membrane, basolateral membrane
Step 1.
Water molecules inside cell cytosol are cleaved into H+ and OH-
Step 2.a
OH- combines with CO2 within cell cytosol (passive diffusion) to form carbonic anhydrase (HCO3)
Step 2.b (apical membrane)
H+ is pumped into stomach lumen alongside K+ being pumped inside cell cytosol with the H+/K+ antiporter pump (ATP expense).
Step 3 (apical membrane)
K+ entering cell cytosol is exported back to stomach lumen through K+ channel to maintain electrochemical gradient of apical membrane.
Step 4 (basolateral membrane)
HCO3/Cl- antiporter imports Cl- inside cell cytosol and exports HCO3
Step 5 (apical membrane)
Cl- is exported to stomach lumen through Cl- channel
How many GLUT transporters are there? Why do we say they are isozymes?
What kind of transporters are they?
What are the transported monosaccharides of GLUT2 and GLUT5?
Where is GLUT1 found?
5 GLUT transporters
Isozymes: different versions of the same enzymes that catalyze the same chemical reaction but that differ in chemical structure, function or regulation.
GLUT transporters are uniporter transporters.
GLUT isozymes specialize in transporting different types of monosaccharides.
GLUT2: glucose, galactose and fructose
GLUT5: only fructose
GLUT1: found in rbc
Is the a higher concentration of glucose in the gut lumen (fed conditions) or in enterocyte cytosol? Why?
Describe the absorption of dietary glucose from the intestinal lumen (Draw it out)
Describe different concentrations of Na+, K+ and glucose in the bloodstream, the cell cytosol and the intestinal lumen.
Key words: K+ channel, GLUT2, Na+/K+ ATPase, Na+/glucose symporter, apical membrane, basolateral membrane, electrochemical gradient, Na+/K+/glucose concentrations
Higher concentration of glucose inside the cytosol because the volume is greater in the gut, meaning glucose is more dispersed than within the cell cytosol (lower concentration in gut).
Step 1 (apical membrane).
Apical membrane has an electrochemical potential of -70mV. Na+/glucose symporter imports glucose and Na+ inside cell cytosol agaisnt glucose’s gradient and with Na+’s gradient. This destabilizes membrane potential, which needs to be re-established.
Step. 2 (basolateral membrane)
Glucose crosses the basolateral membrane towards the bloodstream with GLUT2 transporter.
Step 3. (basolateral membrane)
To re-establish cell’s membrane potential, K+ channels export K+ to the bloodstream.
Step 4. (basolateral membrane)
To re-establish ion concentrations, Na+/K+ ATPase pump imports K+ for export of Na+. This re-establishes Na+ gradient on apical membrane
Concentrations:
Blood: high Na+, low K+, moderate glucose
Cell cytosol: low Na+, high K+, high glucose
Gut lumen: high Na+, low glucose (K+ not relevant).
What is the goal of GLUT? How does it work in simple terms? Where is it found?
How does GLUT work in specific terms? Describe the 5 steps with GLUT1
Key words: outward open, inward open, dissociation constant.
Goal: move glucose from one side of membrane to another
Works by: adopting a variety of conformations in response to stimuli.
Found in a variety of tissues, depending on the isoform. Can be in enterocyte basolateral membranes, cell membranes, etc..
Outward: towards bloodstream
Inwards: towards cell cytosol
- GLUT1 has outward open and inward closed conformation, high affinity for glucose.
- Ligand (glucose) binds to transporter. (Ligand-bound occluded). Induces conformational change to close outwards path.
- Other simultaneous conformational change occurs due to glucose binding resulting in adoption of inward open conformation.
- Glucose affinity is reduced by conformational changes, which releases glucose into cytoplasm to form a ligand-free occluded GLUT1 translocator.
- Now empty GLUT1 translocator undergoes a conformational change resulting in outward open conformation (Step 1)
Where is the Na+/glucose symporter located?
How does Na+/glucose symporter work on a biochemical level during the fed state? 5 steps
Key words: outer vestibule, inner vestibule, outer gate, inner gate, glucose, Na+, association constant
*What about symporter function?
Located on apical membrane of enterocytes (towards gut lumen) to absorb glucose inside enterocyte cells (so that they can then be absorbed into the bloodstream by GLUT)
Fasting state: Na+/glucose symporter is closed.
Fed state:
Step 1. Glucose in bloodstream interacts with outer vestibule, allowing outer gate to open.
Step 2. Outer vestibule guides Na+ to binding site inside the transporter (2Na+ needed for every glucose)
Step 3. Once there are 2 Na+, triggers movement of glucose to bind inside transporter.
Step 4. Electrostatic interactions between substrates and transporter allow it to move and close outer gate on the apical side of the membrane and open the inner gate towards the cytoplasm.
Step 5. As inner gate opens, affinity of Na+ decreases, releasing Na+ into the cytoplasm.
Step 6. Decrease of affinity of glucose after Na+ exits allows glucose to release in the cytoplasm as well.
Step 7. Ligand free transporter can close inner gate and adopt its original conformation.
