Flashcards in Unit 6 - Regulation of CHO Metabolism Deck (23)
what's the difference between enzymes that operate far from equilibrium and near to equilibrium?
far: rate limiting, well suited as control points b/c modulation has significant effect on flux thru a pathway (large negative delta G)
-rate of catalysis limits flux thru that step in a pathway
near: so efficient that a reduction in activity has little/no effect on overall flux
-rate of catalysis is much faster than net flux thru that step
what are the 3 enzymes that operate far from equilibrium during glycolysis?
hexokinase, phosphofructokinase, and pyruvate kinase
why is bypass III (glucose-6-phosphatase) not a good point to regulate glycolysis?
G6P is required for other pathways
-G6P released during glycogen breakdown enters glycolysis after bypass III
why is pyruvate kinase a good point of regulation?
it needs to be turned off during gluconeogenesis b/c [PEP] (substrate) will be elevated
what happens to PFK when an allosteric activator VS inhibitor binds?
activator: PFK assumes conformation that places stabilizing positive charge (R162) near negatively charged substrate
inhibitor: PFK assumes conformation that places destabilizing negative charge (E161) near negatively charged substrate
what stimulates or inhibits PFK? its bypass (II) FBPase?
+ AMP, ADP, F2,6BP
- ATP, cAMP (indirectly)
- AMP, F2,6BP
what is F-2,6-BP structure and regulation? when is it active or inactive?
fructose-2,6-bisphosphate has synthesis and breakdown controlled by carefully regulated bifunctional enzyme (BFE) via hormones
-dephosphorylated state: catalytic site in kinase domain (PFK-2) is active to allow glycolysis
-phosphorylated: catalytic state in phosphotase domain (FBPase-2) is active to allow gluconeogenesis
what stimulates or inhibits pyruvate kinase? pyruvate carboxylase and PEPCK?
- ACoA, ATP, cAMP-dependant phosphorylation
pyruvate carboxylase and PEPCK
which enzymes does glucagon affect?
effects are due to cAMP
-decreases glycolytic enzymes (hexo/glucokinase, PFK)
-increases gluconeogenic enzymes (PEPCK, FBPase, G6Pase)
which enzymes does insulin affect?
decreases PEPCK of glugoneogenesis only
what is the enzyme regulated to make glycogen? to break down glycogen?
to make glycogen: glycogen synthase
to break glycogen: glycogen phosphorylase
how is glycogen phosphorylase regulated? how does this also inhibit glycogen synthase?
increased cAMP activates PKA, which activates phosphorylase kinase (b --> a), which activates glycogen phopshorylase (b --> a)
-active PKA also inhibits glycogen synthase and phosphoprotein phosphatase-1
how is glycogen synthase regulated? how does this also inhibit glycogen phosphorylase?
insulin activates phosphoprotein phosphatase-1, which activates glycogen synthase (b --> a) and reverses all the PKA changes (inactivates glycogen phosphorylase (a --> b), phosphorylase kinase)
how do glucagon and epinephrine affect liver cells?
glucagon: binds to receptor to produce cAMP, stimulate glycogen breakdown, and release of glucose into bloodstream
epinephrine: binds to alpha and beta receptors that increase Ca++ and cAMP respectively, for glycogen degradation
does muscle have glucagon receptors?
no, because they are not responsible for maintaining blood glucose
how do epinephrine and insulin affect muscle cells?
insulin: increases glucose uptake in muscle (and adipocytes) by increasing glucose transporters at cell surface
-increases glycogen and triacylglycerol synthesis
epinephrine: binds to beta-adrenergic receptors to increase cAMP, glycogen degradation, and glycolysis (by increasing availability of G6P)
does moving of GLUT4 receptors from vesicles to membrane happen in brain or liver?
no, only in muscle and adipocytes by insulin
allosteric regulation of glycogen phosphorylase
-when blood glucose is low, GP is phosphorylated (active R conformation)
--even if blood glucose doesn't drop, you must activate phosphorylase if AMP levels rise
-when blood glucose (and ATP and G6P) is high, GP is dephosphorylated (inactive T conformation)
how is pyruvate dehydrogenase complex regulated?
complex contains its own regulatory enzymes E4 and E5 (pyruvate dehydrogenase phosphatase/kinase)
-PDK shuts off E1 by phosphorylating it
-PDP turns on E1 by dephosphorylating it (part of fight-or-flight response)
what activates and inhibits pyruvate dehydrogenase kinase/phosphatase
+ NADH, ACoA
- pyruvate, ADP
what are the product inhibitions of the TCA?
citrate synthase: citrate
isocitrate dehydrogenase: NADH
a-ketoglutarate DH: NADH, SCoA
what are the feedback inhibitions of the TCA?
citrate synthase: SCoA