Regulation of Carbohydrate Metabolism Flashcards
When blood sugar increases:
Insulin is ____
released
Insulin is released, which leads to the
dephosphorylation of:
- PFK-2
- Pyruvate kinase
- Pyruvate dehydrogenase
- Glycogen synthase
- Glycogen phosphorylase
When blood sugar decreases: ____ is released
Glucagon
glucagon release leads to the ______
•PFK-2 (phosphatase active, ↓ F2,6BP)
Pyruvate kinase (inactive)
•Pyruvate dehydrogenase (E1 inactive)
Glycogen synthase (inactive) •Glycogen phosphorylase (active)
phosphorylation
Insulin is released, which leads to the
dephosphorylation of:
PFK-2, Pyruvate kinase, Pyruvate dehydrogenase, Glycogen synthase, Glycogen phosphorylase
leads to active
- Glycolysis
- CAC
- Glycogen synthesis (Glycogenesis)
When blood sugar decreases: Glucagon is released, which leads to the phosphorylation of:PFK-2, Pyruvate kinase, Pyruvate dehydrogenase, Glycogen synthase, Glycogen phosphorylase
this leads to active
Gluconeogenesis
Glycogen breakdown (Glycogenolysis)
enzymes that operate ____equilibrium may be so efficient that a reduction in their activity will have little or no effect on the overall flux.
near
when a reaction is rate limiting
[S] ____ [S]eq
[S] > [S]eq
when rxn is rate limiting
[P] ___ [P]eq
[P] < [P]eq
when rxn is rate limiting
∴ΔG = ___
negative
___ (3) catalyze glycolytic steps that are rate limiting
Hexokinase, Phosphofructokinase, and Pyruvate Kinase
When an enzyme catalyzes a reaction that is near equilibrium, it means that its rate of catalysis is
much faster than net flux through that step
When an enzyme catalyzes a reaction that is ____, it means that its rate of catalysis limits flux through that step in a pathway
highly exergonic
what steps need to be bypassed (bc they are highly exergonic) in glucogenogensis?
the same ones that are rate limiting in glycolysis
Hexokinase, Phosphofructokinase, and Pyruvate Kinase
which point is not the optimal point to regualte glycolysis? why?
Bypass III is not the optimal point to regulate Glycolysis because G6P is required for other pathways
which point IS a good point to regulate glycolysis?
PFK
or pyvutate kinase
why does pyruvate kinase need to be turned off during glucogenogenssi?
the concentration of its substrate, PEP, will be elevated
PFK is allosterically inhibited by
ATP as a feedback inhibitor
___ effectively competes with ATP for binding at the allosteric site
- AMP
- F2,6BP
what speeds up glyciolysis? why?
AMP effectively competes with ATP for binding at the allosteric site signaling
Glycolysis to speed up to replenish the ATP supply
When an allosteric activator binds, PFK assumes a conformation that places a ___ near a ____
stabilizing positive charge (R162) near the negatively charged substrate
when an allosteric inhibitor binds to PFK, the conformation assumed places a
destabilizing negative charge (E161) near the negatively charged substrate
F2,6BP prevents ____ because it competes with ATP for binding on PFK
feedback inhbiition of glyolysis
, F2,6BP and AMP bind to an allosteric site on ____and inhibit, thereby slowing Gluconeogenesis
FBPase
effect of F2,6BP and AMP on gluyconeogensis?
slow gluconeogensis
difference between FBP and F2,6BP structurally?
The second phosphoryl on F2,6BP is on the C2 hydroxyl instead of on the C1 hydroxyl as is the case for FBP
In the dephosphorylated state, the catalytic site in the ____ domain ss active
kinase domain, called PFK-2
what is PFK-2?
catalytic site in the kinase domain
In the phosphorylated state, the catalytic site in the ____ domain is active
phosphatase domain, FBPase-2
increased CAMP
increased enzyme phoshporylation
activation of FBP-ase-2 and inactivation of PFK-2
dec F26P
- inhibition of PFK
- activation of FBPase
increased glucogenosesis
blood Glu concentration is high, insulin promotes decreased enzyme phosphorylation resulting in increased ___
F2,6P —> inc glycolysis, dec gluconeogesnsis
Hormonal regulation of ___in response to blood [Glu] allows selective activation of the pathway needed, while turning off the pathway not needed
[F2,6BP]
Pyruvate Kinase is activated by
FBP
Pyruvate Kinase is also inhibited by
- phosphorylation induced by Glucagon
- acetyl coa
- atp
Pyruvate Carboxylase is activated by ____
Acetyl-CoA
Glucagon causes a decrease in the level of
Glucokinase & PFK (Glycolytic enzymes)
Glucagon causes an increase in the level
PEPCK, FBPase, and G6Pase ( Gluconeogenic enzymes)
Insulin causes a decrease in the level of the
PEPCK (Gluconeogenic enzyme)
The synthesis/breakdown pathways of glycogen can be thought of as one big bypass. Only ____ is shared
phosphoglucomutase
In the pathway leading to glycogen, ____is the enzyme regulated
glycogen synthase
In the pathway that breaks down glycogen, ____is the enzyme regulated
glycogen phosphorylase
An increase in cAMP activates Protein Kinase A which activates Phosphorylase Kinase, which activates ____
Glycogen Phosphorylase
Active PKA nd Phosphorylase Kinase inhbiit
Glycogen Synthase
Protein Kinase A inactivates
Phosphoprotein Phosphatase-1
Insulin activates____ and reverses all of the changes caused by an active Protein Kinase A
Phosphoprotein Phosphatase-1
Glucagon binds to a liver cell receptor which produces
cAMP –> glycogen breakdown –> release of Glucose to blood stream
___ and ___binds to a liver cell receptor which produces cAMP –> glycogen breakdown –> release of Glucose to blood stream
Epinephrine and Glucagon
Muscle cells have no ____ receptor
Glucagon receptor
they are not responsible for maintaining blood glucose
However, muscle cells still need to respond to ____ to increase availability of Glu-6-P for ATP production
epinephrine
Insulin increases ___ in muscle
increases number of glucose transporters —> inc Glu uptake
inc glucose uptake in muscle leads to
inc glycogen sythnesis
inc adipocytes uptake in muscle leads to
increased synthesis of triacylglycerols
When blood Glu is low, Phosphorylase will be in the ____ and ___
Phosphorylated form and in the active r confirmation
When blood Glu is high, ATP and G6P will be high and dephosphorylated Phosphorylase will be in the ____ confirmation
inactive T conformation
what are E4 and E5?
Pyruvate Dehydrogenase Complex
the Pyruvate Dehydrogenase Complex kinase is activated by
NADH and Acetyl-CoA to phosphorylate and inactivate E1
___ and ____ inhibit the Kinase of the Pyruvate Dehydrogenase Complex
pyruvate and ADP
Pyruvate Dehydrogenase Complex
The Phosphatase is activated by____to convert E1 back to the active form
calcium ion
Pyruvate Dehydrogenase Complex
product inhibition of e3 occurs by
nadh
Pyruvate Dehydrogenase Complex
E2 is inhibited by
Acetyl-CoA
what inhbiits cit synthease?
citrate
Succ-CoA
what inhibits isocitrate dehydrogenase?
NADH
ATP
what inhbiits α-ketoglutarate DHase
NADH and Succ-CoA
what activates isocitrate dehydrogenase?
ADP
