Carbohydrate metabolism Flashcards
Once Glucose is converted to Glucose-6-P it can enter several pathways? What are they?
1.) glycolysis
2.) PPS
3.) Glycogenesis
What enzyme is needed to commit glucose-6-P to glycolysis?
PFK-1 (main switch)
glycolysis energy yield
2 ATP
2 NADH
3 irreversible reactions of glycolysis?
hexokinase, PFK-1, Pyruvate kinase
Hexokinase is reversibly regulated by what? That’s an example of what? What causes it? (in muscle)
Reversibly regulated by glucose-6-phosphate
This is an example of product inhibition
When cellular concentrations of glucose-6-P rise above normal, Hexokinase is temporarily inhibited to bring rate of glucose-6-P into balance with its rate of utilization
What kind of regulation is PFK-1 under?
allosteric regulation
What is the most important allosteric regulator? Why?
Fructose 2, 6- bisphosphate, because it activates PFK-1 and stimulates glycolysis
Inhibits FBP-1, slowing gluconeogenesis
How is Fructose 2,6 bisphosphate formed? Catalyzed by?
formed by phosphorylation of fructose-6-P
catalyzed by PFK-2
When 2 enzymes are working together what other kind of control is used?
covalent modification
Glucagon vs insulin
1.) favor what state?
2.) favors phosphorylation?
3.) covalent modification?
4.) glucokinase, PFK-1, pyruvate kinase?
5.) FBP-2?
6.) PEP carboxykinase
1.) G= = fasting I=fed
2.) G = favors phosphorylation I = does not.
3.) G= = yes, favors I= no, disfavors
4.) G= reduces expression I= promotes transcription (and activation of PFK-1)
5.) G= activation, by lowering levels of F-2,6BP I= inhibition
6.) G= induces transcription
What is pyruvate kinase allosterically regulated by?
inhibited:
1.) ATP
2.) Acytyl-CoA
3.) fatty acids
activation:
1.) fructose 1,6- bisphosphate
fructose, mannose and galactose are converted into what?
glycolytic intermediates
Fructose vs glucose
1.) fructose = Faster and converted to FAT more readily
4 conversions of pyruvate.
1) acetyl CoA –> enter into CAC
2) Oxaloacetate –> enter into GNG
catalyzes conversion = Pyruvate carboxylase (allosterically activated by acetyl CoA)
2 ATP required. 1 to make oxaloacetate and 1 GTP to make
3) Lactate (Cori cycle)
*Acetyl CoA is a allosteric activator of pyruvate carboxylas
FBP-1
allosterically inhibited by AMP and F2,6-BP
What 2 enzymes work in tandem?
PFK-2 and FBPase-2
Purpose of PPS?
Generates two main products:
1.) NADPH
2.) Ribose-5-Phosphate (“pentose phosphates)
Also generates Fructose-6-Phosphate and glyceraldehyde-3-Phosphate, which can feed back into glycolysis
2 phases of PPS? reversible or irreversible? steps? generates? functions?
1.) oxidative = irreversible (1-3), 2 NADPH, reduces glutathione, (GENERATION)
2.) non-oxidative = reversible (4-8), (CONVERSION)
What does glutathione do? AA structure?
Neutralizes (reduces) hydrogen peroxide to water by donating H’s
glycine, cysteine, and glutamic acid.
Rate limiting step of the oxidative phase of PPS? enzyme?
Glucose-6-P –> 6-phosphoglucono-𝛿-lactone
Enzyme: glucose-6-Phosphate dehydrogenase (G6PD)
Regulated by ratio of NADPH:NADP+
High NADPH:NADP+ ratio inhibits G6PD
G6PD deficiency is what kind of trait?
x-linked
What is riboluse-5-P converted into during the non-oxidative phase of PPS?
ribose-5-P OR glycolytic intermediates
What form is glucose stores as? What form? Where?
polymeric, glycogen, liver and skeletal muscle
Glucose is transferred onto a growing chain of glycogen as ____________, by what enzyme?
UDP-glucose, glycogen synthase
Amylo-α(1,4–>1,6) glucosyl transferase AKA what?
branching enzyme
What does glycogen synthase require in order to initiate a new glycogen chain? What does it contain? Where is it found?
Primer, contains pre-formed (alpha14) polyglucose chain with at least 4-8 glucose residues
Found within glycogenin
Glycogenolysis? enzymes.
breakdown of glycogen into glucose.
glycogen phosphorylase = catalyzing the removal of glucose units from glycogen and converting them into glucose-1-phosphate.
phosphoglucomutase = This glucose-1-phosphate is then converted to glucose-6-phosphate (which can either enter glycolysis for energy production or be converted back to free glucose to be released into the bloodstream.
glucose-6-phosphate = The liver can then convert glucose-6-P into glucose (**3rd bypass reaction of gluconeogenesis)
In glycogenolysis, what is the function of a de-branching enzyme?
Cleaves α (1 –> 4) linkages from the non-reducing ends until 4 units away from a branch point
Glucose is released as glucose-1-P
Once all chains degraded to within 4 units of a branch point, the molecule is called a LIMIT DEXTRIN
What are the 2 regulated enzymes in glycogen metabolism? Activated or inhibited?
Initially catalyzed by the SAME PROTEIN: PKA (activated by CAMP)
glycogen synthasen: allost. activated by glucose-6-P
deactivated by phosphorylation
glycogen phosphorylase:
Allosterically inhibited by:
Glucose-6-P
ATP
Free glucose (in the liver only)
Allosterically activated by AMP (muscle only)
activated by phosophorylation
Hormonal control of glycogen metabolism. Glucagon vs. insulin
covalent modification=hormonal control
In the presence of GLUCAGON (and epinephrine):
Glucagon binds to its GCPR
G⍺s activates adenylyl cyclase –> cAMP levels rise
PKA phosphorylates glycogen synthase, rendering it INACTIVE
Glycogenesis is inhibited
PKA phosphorylates glycogen phosphorylase kinase, rendering it ACTIVE
Glycogen phosphorylase kinase phosphorylates glycogen phosphorylase, rendering it ACTIVE
Glycogenolysis promoted
In the presence of INSULIN
Insulin promotes the breakdown of cAMP and thus inactivation of PKA
Insulin activates protein phosphatase 1, which removes the phosphate group from glycogen synthase, rendering it active
Glycogenesis is promoted
Insulin promotes the breakdown of cAMP and thus inactivation of PKA
Insulin activates protein phosphatase 1, which removes the phosphate group from:
Glycogen phosphorylase kinase & Glycogen phosphorylase, rendering them both inactive
Glycogenolysis is inhibited
2 major roles of branching of glycogen?
Increase solubility and increase sites for synthesis and degration
What is the long name of the branching enzyme?
amylo-4,6-transferase
