ch 15 part 2 Flashcards
what amino acids can be phosphorylated
Ser Thr and Tyr
at normal blood ph 7.4, what charge does a phosphorylated AA have?
-1 charge
at normal blood ph 2.1, what charge does a phosphorylated AA have?
-2 charge
what kind of enzyme is glycogen phosphorylase
a hydrolase enzyme
how does glycogen phosphorylase get activated
by adding a phosphate group to it
what does glycogen phosphorylase do
it cleaves branches pieces of glucose on glycogen through hydrolysis
what does glycogen synthase do
it creates more glycogen
how is glycogen synthase activated
by removing a phosphate group
step one of the pathway in which enzymes/proteins result the phosphorylation of glycogen phosphorylase
- hormones (epinephrine or glucagon) will bind to a membrane receptor and this will release a G protein that binds and activates adenylate cyclase which is a transmembrane enzyme.
what hormones start the pathway for glycogen phosphorylase
epinephrine or glucagon
step two of the pathway in which enzymes/proteins result the phosphorylation of glycogen phosphorylase
- adenylate cyclase will catalyze the cyclization of ATP to cyclic AMP or cAMP
step three of the pathway in which enzymes/proteins result the phosphorylation of glycogen phosphorylase
- cAMP binds to the regulatory units in Protein kinase A making PKA active
step four of the pathway in which enzymes/proteins result the phosphorylation of glycogen phosphorylase
- PKA activates a kinase by phosphorylation
step five of the pathway in which enzymes/proteins result the phosphorylation of glycogen phosphorylase
- active kinase activates glycogen phosphorylase also by phosphorylation
step six of the pathway in which enzymes/proteins result the phosphorylation of glycogen phosphorylase
- glycogen phosphorylase catalyzes the hydrolysis of glycogen to glucose
what enzyme makes cAMP
adenylate cyclase
Protein kinase A regulates what two enzymes
GP and GS
how does PKA make phosphorylase kinase active
adding phosphate group
how does PKA make GS inactive
adding phosphate group
what occurs when you phosphorylate both GS and GP
GS becomes inactive and GP becomes active to cleave glucose units
why does PKA phosphorylate both GS and GP
GS is phosphorylated to become inactive and GP comes active after adding the phosphate group. this occurs so that GS doesnt make more glycogen when GP is trying to break it down to use it for energy.
what hormone activates GP
glucagon or epinephrine
what hormone activates GS
insulin
what is mechanism of action for GP and GS
MOA is phosphorylation of GP and dephosphorylation of GS
how does insulin activate GS
it activates phosphatases which deactivates GP by removing group and activates GS by this form
predict if these alterations would increase/decrease/ not change the amount of glycogen in the liver:
mutation of ser to ala in GP
decrease because we can only phosphorylate -OH groups and Ala is neutral and doesnt have -OH group
predict if these alterations would increase/decrease/ not change the amount of glycogen in the liver:
addition of epinephrine
increase because this is the starting hormone for this pathway
predict if these alterations would increase/decrease/ not change the amount of glycogen in the liver:
mutation that causes adenyl cyclase to always be active
increase because it no longer need hormones to start it so its active all the time
predict if these alterations would increase/decrease/ not change the amount of glycogen in the liver:
serine to Thr in GP
no change because both have -OH group
what are the two inhibitors of GP
insulin, increase ATP, and increase glucose 6 phosphate are all negative heterotropic effectors deactivating GP
what is an activator for GP
Amp is a positive heterotropic effector of GP because it uses AMP not ATP
what are the 3 main characteristics of myoglobin
- stores oxygen at the tissue level 2. its a single peptide chain 3. obeys michaelis menten kinetics
what are the 5 main characteristics of hemoglobin
- its job is to bind to O2 at the lungs 2. transports O2 3. 4 polypeptide chains 4. allosteric enzyme 5. has cooperativity
what do inhibitors do to hemoglobin
it forces the hemoglobin to release oxygen to the tissues
what are inhibitors to hemoglobin
CO2 and low PH causing high acidity
what are the five atoms (molecule/ligand) coordinated with the iron in the heme group in deoxygenated hemoglobin
-4 nitrogens on pyrrole rings -nitrogen on the proximal histidine
what are the six atoms (molecule/ligand) coordinated with the iron in the heme group in oxygenated hemoglobin
-4 nitrogens on pyrrole rings - 1 nitrogen on the proximal histidine -O2 when oxygenated
true or false: Hemoglobin is a tetramer while myoglobin is a monomer
True
true or false: hemoglobin exhibits a sigmoidal (S curve) while myoglobin exhibits a hyperbolic curve
True
true or false: hemoglobin exhibits O2 binding cooperativity while myoglobin does not
True
true or false: hemoglobin exhibits lower degree of O2 saturation at all physiologically relevent partial pressures of O2 than does myoglobin does
True
from a physical standpoint, how does binding of one O2 ligand impacts the interactions between Hb subunits resulting in positive cooperativity
O2 (the sixth ligand) binds, then pulls on the Fe2+, which causes the heme to flatten, which then causes the proximal His to be pulled, this changes the shape of the subunits all around
explain from a thermodynamic standpoint, the nature of + cooperativity of O2 binding to hemoglobin (why does the binding affinity increase when one or more O2 molecules are already bound.
it makes the other parts of the protein go into the R state making it more readily available to bind with other O2 molecules
why would a person with CO poisoning be places in an oxygen tent
CO is a competitive inhibitor of Oxygen so you need to overpower its high affinity with substrate concentration to outcompete the CO.
given that small amounts of CO will kill a person, which has a lower P50 CO or O2
CO has a lower KM due to it having a higher affinity to hemoglobin
considering R to T equilibrium, how does the equilibrium shift when O2 binds to Hb
moves to R<—T
considering R to T equilibrium, how does the equilibrium shift when H+ hinds to Hb
moves to T<—R because remember low pH means high acidity which is an inhibitor
how does the binding of H+ affect the release of O2 by HB
the distal His pulls on the O2 more strongly so that the O2 pops out and is no longer a ligand
what effect does alkalemia (ph increase) due to hyperventilation have on the oxygen binding affinity of hemoglobin
P50 decreases and oxygen affinity increases
what is 2,3 BPG
allosteric inhibitor of Hemoglobin, lowers O2 affinity
where does 2,3 BPG bind in HB? How does the binding occur?
allosteric site is the central cavity and the binding occurs by the (-) part of the 2,3 BPG attraction to the (+) nitrogen of His and Lys
what increases the production of 2,3 BPG
low PH acidic conditions
what is a short term adaption to high altitude and low O2 conc? long term?
increase the inhibitor to release O2. long term: more red blood cells
what happens if a mutation changes Lys to val in the allosteric site
2,3 BPG will not bind at the allosteric site as tightly due to difference in charge which causes the release of O2
what is different between fetal Hb and adult Hb
fetal Hb has Ser instead of Lys which causes it to have a higher affinity of O2
O2 is what kind of effector
positive homotropic effector
Co2, H+, and 2,3 BPG are what kind of effector
negative heterotropic effectors
what disease causes children to not be able to turn their fetal hemoglobin to adult hemoglobin
thalassemia (Hb binding to O2 TOO tighetly)
in adults, fetal hemoglobin production can be reactivated pharmacologically which is useful in what disease?
sickle cell anemia, O2 doesnt bind well to Hb here
explain why Hb S molecules aggregate into long chainlike polymeric structures
a single AA substitution in the B chains of HB causes sickle cell anemia (Glu is replaced by val which protrudes and fits into the EF pocket of another Hb S molecule. The val side chain acts like a hook as it protrudes out and causes the red blood cells to be sticky as well.
the oxygen dissociation curve for hemoglobin reflects allosteric effects that result from the interaction of Hemoglobin with O2, Co2, H+, and 2,3 BPG. all of the following structural changes occur in the hemoglobin molecules when O2, CO2, H+, and 2,3-BPG bind except: T or F
The binding of O2 pulls the iron into the plane of the heme and causes a change in the interaction of all four globin subunits, mediated through His F8
True
the oxygen dissociation curve for hemoglobin reflects allosteric effects that result from the interaction of Hemoglobin with O2, Co2, H+, and 2,3 BPG. all of the following structural changes occur in the hemoglobin molecules when O2, CO2, H+, and 2,3-BPG bind except:
2,3-BPG binds at a single site between the four globin subunits in deoxyhemoglobin and
stabilizes the deoxyhemoglobin form by cross-linking the beta subunits.
True
the oxygen dissociation curve for hemoglobin reflects allosteric effects that result from the interaction of Hemoglobin with O2, Co2, H+, and 2,3 BPG. all of the following structural changes occur in the hemoglobin molecules when O2, CO2, H+, and 2,3-BPG bind except:
The deoxy form of hemoglobin has a greater affinity for H+ because the molecular environment of His and the alpha-NH2 groups of the chains changes, rendering these groups less
acidic when O2 is released
True
The oxygen dissociation curve for hemoglobin reflects allosteric effects that result from the interaction of hemoglobin with O2, CO2, H+, and 2,3-BPG. All of the following structural changes
occur in the hemoglobin molecules when O2, CO2, H+, and 2,3-BPG bind except:
the binding of CO2 stabilizes the oxy form of hemoglobin
False
adult hemoglobin has what charge residue
positive charge
hemoglobin inhibitor has what charge residue
negative charge
fetal hemoglobin has what charge
neutral
why is it so hard for an inhibitor to make fetal hemoglobin release oxygen to tissues
because the inhibitor is negative and the fetal Hb is neutral so theres no attraction like adult Hb that has a positive charge
what amino acid does HbA have? HbF?
HbA has His and HbF has Serine
