Module 6, L1 Flashcards
(24 cards)
What do patients with severe diabetes have high amounts of and how are these produced?
Patients would have alot of ketone bodies, which are produced by the breakdown of FA’s
What methods do animals use to bind and transport oxygen?
Animals use myoglobin and hemoglobin to transport/bind oxygen
What do enzymes do? How do they achieve their function?
How do enzymes bind?
Enzymes are what help accelerate the rates of reactions by reducing the transition state energy needed for a reaction.
- this doesn’t affect directionality (can go in both directions!)
- They bind via LOCK/KEY mechanisms
How do vitamins factor into the job of enyzmes?
..enzymes may require them for catalysis
What point mutation of Hb can result in a similar Mb binding curve?
This can occur when you mutate histidine (which is postively charged) to something uncharged (like glycine).
How would you describe the O2 binding curves of myoglobin and hemoglobin?
Myoglobin- has a HYPERBOLIC curve. Initially has a steep slope, indicating tight and rapid binding even at low pressure
- at 3 torr, 50% of O2 binds to it
Hemoglobin- has a SIGMODIAL (S shape) curve. B/c it has 4 subunits, each one has a different O2 affinity where initially the affinity for 02 is LOW, but after O2 binds, the binding affinities of the next subunits increases
How would you describe the O2 binding curves of myoglobin and hemoglobin?
Myoglobin- has a HYPERBOLIC curve. Initially has a steep slope, indicating tight and rapid binding even at low pressure
- at 3 torr, 50% of O2 binds to it
Hemoglobin- has a SIGMODIAL (S shape) curve. B/c it has 4 subunits, each one has a different O2 affinity where initially the affinity for 02 is LOW, but after O2 binds, the binding affinities of the next subunits increases
How would you describe the Hb binding mechanism?
Cooperativity- this is caused by a small change in subunit structure when O2 binds
How does Hb and Mb look with and without O2 bound?
Deoxy-Hb: Fe is out of plane (0.6 A) in the direction of histidine and F helix
Oxy-Hb: O2 binding leads to Fe being in plane (0.6 A movement). This movement is ampified by a 1 A movement of Helix F due to the movement of histidine side chain– such movement can lead to molecules attached to F helix to move as well
**Mb F helix is NOT affected/undergo conformational changes due to O2 binding
What are the two dynamic conformational states of Hb? What are these states dictated by?
The R and T state are both dictated by conformation change.
Tense/T state: low affinity for O2– Fe is out of plane
Relaxed/R state: high affinity of O2– Fe is in plane with heme
Ex: As O2 binds it will transition from T to R state (same happens in lungs); in tissue as it releases O2 it will trasition back to the T state to release the other O2 molecules
What is the Bohr effect? How does it affect O2 binding?
this is when pH plays an effect on T and R state where:
- Decrease in pH of a cell will decrease O2 binding/affinity
- The pKa’s of aa’s at the surface of subunits stabilize these states and are sensitive to electrostatic interactions and proton concentrations
How does the Bohr effect relate to severe diabetes? How would this look like on an O2 curve?
Patients with severe diabetes will produce alot of ketone bodies that are very acidic that will increase proton concentration, this change will decrease O2 binding– stabilizing T state
- In comparison to purified Hb, those with diabetes will have an S curve shifted to the RIGHT
What is A1c?
A1c is a biomarker for diabetes and exists in the T state
- this occurs because high blood glucose causes a modification to hemoglobin to form this
What are the 3 things that stabilize the T states? Draw how they look on a O2 curve.
- pH/Bohr effect
- 2,3-BPG
- CO2
How does 2,3, BPG regulate O2 binding/stabilize the T state?
Both the R and T state are regulated by 2,3-BPG, product of glycolysis where an increase in BPG leads to a decrease in binding affinity–promoting the T state by forming H bonds and salt bridges
How does CO2 stabilize the T state? (2 statements)
- 95% CO2 produced by cells will react with O2 to form protons and bicarbonates, increasing proton concentration– this leads to the release of O2.
- 5% of CO2 will react with the N terminal NH3 group of hemoglobin to form carbamate, promoting the T state
What are the classifications of enzymes/biological reactions (just list)?
- Oxioreductase/redox
- Transferase
- Hydrolase
- Lyase/group elimination
- Isomerase
- Ligase
- Redox
Catalyzed by enzymes called 1. dehydrogenases: catalyze CH oxidation reaction where a hydride is removed from CH bond
Ex: Pyrivate +NADH —> lactate + NAD+
2. oxioreductases/ reductases
- Transferase
transfers a group from one molecule to another
Ex: Kinases/phosphotransferase- will transfer a phosphate group from ATP to substrate
Glucose +ATP–> ADP + Glucose-6-Phosphate
- Hydrolase
catalyze reactions where water functions as nucleophile
Ex: peptidases cleave peptide bonds
-General rxn: A-B + H2O –> A-OH + B-H
- Lyase
breaks C-C and C-O bonds involved in group eliminaton
- Aldolases: catalyze C-C bond breakage in F-1,6-BP to form DHAP and ..
- Decarboxylases: catalyzes elimination of CO2
- Isomerase
catalyze shifts in location of double bonds (occurs b/w adjacent C-C bonds)
Ex: C-6-P –> F-6-P
- Ligase
uses ATP IN reaction mechanism where ATP hydrolysis relases enegrgy to drive reaction and acts as a good leaving group
What are co-enzymes and co-factors used for? List some examples of co-enzymes.
Cofactors can be used by enzymes to help catalyze a reaction
- includes inorganics such a metal ions, organics like vitamins, prosthetic groups (heme) or coenzymes ( NAD+/NADH, FAD+/FADH, and CoA)
