Carbohydrate metabolism

Question 1

Once Glucose is converted to Glucose-6-P it can enter several pathways? What are they?

Answer 1

1.) glycolysis
2.) PPS
3.) Glycogenesis

Question 2

What enzyme is needed to commit glucose-6-P to glycolysis?

Answer 2

PFK-1 (main switch)

Question 3

glycolysis energy yield

Answer 3

2 ATP
2 NADH

Question 4

3 irreversible reactions of glycolysis?

Answer 4

hexokinase, PFK-1, Pyruvate kinase

Question 5

Hexokinase is reversibly regulated by what? That’s an example of what? What causes it? (in muscle)

Answer 5

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

Question 6

What kind of regulation is PFK-1 under?

Answer 6

allosteric regulation

Question 7

What is the most important allosteric regulator? Why?

Answer 7

Fructose 2, 6- bisphosphate, because it activates PFK-1 and stimulates glycolysis

Inhibits FBP-1, slowing gluconeogenesis

Question 8

How is Fructose 2,6 bisphosphate formed? Catalyzed by?

Answer 8

formed by phosphorylation of fructose-6-P
catalyzed by PFK-2

Question 9

When 2 enzymes are working together what other kind of control is used?

Answer 9

covalent modification

Question 10

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

Answer 10

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

Question 11

What is pyruvate kinase allosterically regulated by?

Answer 11

inhibited:
1.) ATP
2.) Acytyl-CoA
3.) fatty acids
activation:
1.) fructose 1,6- bisphosphate

Question 12

fructose, mannose and galactose are converted into what?

Answer 12

glycolytic intermediates

Question 13

Fructose vs glucose

Answer 13

1.) fructose = Faster and converted to FAT more readily

Question 14

4 conversions of pyruvate.

Answer 14

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

Question 15

FBP-1

Answer 15

allosterically inhibited by AMP and F2,6-BP

Question 16

What 2 enzymes work in tandem?

Answer 16

PFK-2 and FBPase-2

Question 17

Purpose of PPS?

Answer 17

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

Question 18

2 phases of PPS? reversible or irreversible? steps? generates? functions?

Answer 18

1.) oxidative = irreversible (1-3), 2 NADPH, reduces glutathione, (GENERATION)
2.) non-oxidative = reversible (4-8), (CONVERSION)

Question 19

What does glutathione do? AA structure?

Answer 19

Neutralizes (reduces) hydrogen peroxide to water by donating H’s

glycine, cysteine, and glutamic acid.

Question 20

Rate limiting step of the oxidative phase of PPS? enzyme?

Answer 20

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

Question 21

G6PD deficiency is what kind of trait?

Answer 21

x-linked

Question 22

What is riboluse-5-P converted into during the non-oxidative phase of PPS?

Answer 22

ribose-5-P OR glycolytic intermediates

Question 23

What form is glucose stores as? What form? Where?

Answer 23

polymeric, glycogen, liver and skeletal muscle

Question 24

Glucose is transferred onto a growing chain of glycogen as ____________, by what enzyme?

Answer 24

UDP-glucose, glycogen synthase

Question 25

Amylo-α(1,4–>1,6) glucosyl transferase AKA what?

Answer 25

branching enzyme

Question 26

What does glycogen synthase require in order to initiate a new glycogen chain? What does it contain? Where is it found?

Answer 26

Primer, contains pre-formed (alpha14) polyglucose chain with at least 4-8 glucose residues

Found within glycogenin

Question 27

Glycogenolysis? enzymes.

Answer 27

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)

Question 28

In glycogenolysis, what is the function of a de-branching enzyme?

Answer 28

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

Question 29

What are the 2 regulated enzymes in glycogen metabolism? Activated or inhibited?

Answer 29

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

Question 30

Hormonal control of glycogen metabolism. Glucagon vs. insulin

Answer 30

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

Question 31

2 major roles of branching of glycogen?

Answer 31

Increase solubility and increase sites for synthesis and degration

Question 32

What is the long name of the branching enzyme?

Answer 32

amylo-4,6-transferase