Glycogen Metabolism and Pentose Phosphate Pathway Flashcards

1
Q

___________ is a glucose polymer (up to 100k molecules of glucose/molecule of glycogen). It is a ______________.

Molecules of __-glucose are linked together by _____________ bonds.

A

Glycogen; homopolysaccharide

D; O-glycosidic

Glycosidic bond: a bond linking a sugar with another molecule (in glycogen, this other molecule is another glucose). There are O-, N-, and P- glycosidic bond.

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2
Q

The intra chain O-glycosidic bonds are α__–>__

The inter chain O-glycosidic bonds are α__–>__

A

1; 4

1; 6 (side chain of glycogen)

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3
Q

What are reducing sugars?

A

Reducing sugars are sugars capable of acting as a reducing agent (give electrons to an oxidizing agent) since they still have a free ALDEHYDE or KETONE group.

A reducing sugar needs to have an HEMIACETAL or HEMIKETAL group.

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4
Q

Match the definitions to their terms;

1) Hemiacetal
2) Hemiketal
3) Anomeric carbon

A) a carbon at the center of an hemiacetal or hemiketal functional group.

B) a carbon which is part of an ether bond (R-O-R’) but is also attached to an alcohol (OH). derived from ALDEHYDE (e.g. glucose).

C) a carbon which is part of an ether bond (R-O-R’) but is also attached to an alcohol (OH). derived from KETONE (e.g. fructose)

A

Hemiacetal: a carbon which is part of an ether bond (R-O-R’) but is also attached to an alcohol (OH). derived from ALDEHYDE (e.g. glucose).

Hemiketal: a carbon which is part of an ether bond (R-O-R’) but is also attached to an alcohol (OH). derived from KETONE (e.g. fructose)

Anomeric carbon: a carbon at the center of an hemiacetal or hemiketal functional group.

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5
Q

There is one reducing end in a glycogen molecule and all the other ends are non-reducing ends.

Why?

A

The non-reducing ends are the site of glycogen metabolism (catabolism/anabolism), so the more non-reducing ends there are, the quicker the glycogen is metabolized.

*the branches of glycogen allow for more non-reducing ends.

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6
Q

Why is glucose not simply stored as glucose but rather glycogen?

A

One molecule of glycogen displays a third of the OSMOTIC PRESSURE when compared to the number of glucose monomers constituting this glycogen molecule.

If the glucose molecules were stocked unchanged in the cell, the cell would be highly osmotic, so WATER WOULD PERMEATE INTO THE CELL, and pumping out the excess water would be too costly in energy, the cells would BURST OPEN.

This allows the cell to keep a NEGATIVE CONCENTRATION GRADIENT OF GLUCOSE between the interior and the exterior of the cell, therefore facilitating glucose entry (tricks the cell into thinking there is no glucose).

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7
Q

Where is glycogen stored in?

A

1) Liver (public usage)
2) Muscles (private usage)

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8
Q

How is the glycogen used in the liver vs the muscles?

A

Glycogen in the liver: in case of need, the liver EXPORTS glucose from glycogen breakdown towards other organs (mainly brain)

Glycogen in the muscles: muscles use glycogen during MUSCLE CONTRACTIONS.

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9
Q

Liver contains _____ of stored glycogen in the body (1/8th of liver weight), while muscle contains _____ of stored glycogen (0.8% of muscle weight).

Liver glycogen reserve can be exhausted in less than _____ hours, while muscle glycogen reserve can be exhausted in __ to __ hours of exercise.

A

1/3; 2/3

24; 1-2

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10
Q

(T/F) Glycogen is stored in the cytoplasm, glycosome and the endoplasmic reticulum.

A

False!

Glycogen is stored in the MITOCHONDRIA, glycosome (glycogen granuels) and the endoplasmic reticulum.

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11
Q

What is the difference between glycogenesis and glycogenolysis?

A

Glycogenesis: anabolism of glycogen (synthesis of glycogen to store glucose)

Glycogenolysis: catabolism of glycogen (from diet/endogenous glycogen) into glucose-1-phosphate

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12
Q

Where does glycogen metabolism occur?

A

1) GUT (postprandial period): digestive catabolism of food glycogen. allows the production of glucose for distribution to glycogen storage areas and organs

2) LIVER (glucostat): glycogen synthesis during postprandial period, glycogen breakdown between meals.

3) MUSCLES: glycogen synthesis when the muscle is at rest, glycogen breakdown when muscles are contracting.

*glycogenesis occurs in the liver + muscles

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13
Q

Glycogen synthesis or degradation depends on:

A

1) the nutritional state of the organism (right after eating: synthesis, between meals: breakdown)

2) the need for energy

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14
Q

Match the following steps of glycogenesis to their definitions:

1) Reaction 1
2) Reaction 2
3) Reaction 3
4) Reaction 4
5) Reaction 5
6) Reaction 6

A) Glucose-1-phosphate (G1P) is ACTIVATED in UDP-glucose by the UDP-GLUCOSE PYROPHOSPHORYLASE.

B) Building side chains (α1–>6) bonds done by AMYLO-(1,4–>1,6)-TRANSGLYCOSYLASE.

C) Extension of the new glycogen molecule by elongation of the branches and formation of new (α1–>4) bonds bu GLYCOGEN SYNTHASE and addition of new side branches by AMYLO-(1,4–>1,6)-TRANSGLYCOSYLASE.

D) Glucose is PHOSPHORYLATED to form Glucose-6-phosphate (G6P) by HEXOKINASE.

E) Synthesis of linear chains (α1–>4); glucose from UDP-glucose is transferred to the nonreducing end of a glycogen primer or a linear chain undergoing elongation done by GLYCOGEN SYNTHASE.

F) Glucose-6-phosphate (G6P) is ISOMERIZED to glucose-1-phosphate (G1P) by PHOSPHOGLUCOMUTASE.

A

Reaction 1: Glucose is PHOSPHORYLATED to form Glucose-6-phosphate (G6P) by HEXOKINASE.

Reaction 2: Glucose-6-phosphate (G6P) is ISOMERIZED to glucose-1-phosphate (G1P) by PHOSPHOGLUCOMUTASE.

Reaction 3: Glucose-1-phosphate (G1P) is ACTIVATED in UDP-glucose by the UDP-GLUCOSE PYROPHOSPHORYLASE.

Reaction 4: Synthesis of linear chains (α1–>4); glucose from UDP-glucose is transferred to the nonreducing end of a glycogen primer or a linear chain undergoing elongation done by GLYCOGEN SYNTHASE.

Reaction 5: Building side chains (α1–>6) bonds done by AMYLO-(1,4–>1,6)-TRANSGLYCOSYLASE.

Reaction 6: Extension of the new glycogen molecule by elongation of the branches and formation of new (α1–>4) bonds bu GLYCOGEN SYNTHASE and addition of new side branches by AMYLO-(1,4–>1,6)-TRANSGLYCOSYLASE.

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15
Q

Match the following steps of glycogenesis to their definitions:

1) Reaction 1
2) Reaction 2
3) Reaction 3
4) Reaction 4

A) Reversible reaction! Taking the phosphate on C6 and moving it to C1 of G6P!

B) UDP is released. Since UDP-glucose is a high-energy compound, reaction is exergonic and irreversible!

C) There is an investment of ATP; irreversible! Catalyzed by hexokinase I, II, III in the muscles, and by glucokinase in the liver.

D) Reaction is driven by the hydrolysis of the pyrophosphate from the uridine triphosphate (UTP). Irreversible! The activated intermediate, UDP-glucose, used as building blocks in the growing glycogen chain.

A

Reaction 1: There is an investment of ATP; irreversible! Catalyzed by hexokinase I, II, III in the muscles, and by glucokinase in the liver.

Reaction 2: Reversible reaction! Taking the phosphate on C6 and moving it to C1 of G6P!

Reaction 3: Reaction is driven by the hydrolysis of the pyrophosphate from the uridine triphosphate (UTP). Irreversible! The activated intermediate, UDP-glucose, used as building blocks in the growing glycogen chain.

Reaction 4: UDP is released. Since UDP-glucose is a high-energy compound, reaction is exergonic and irreversible!

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16
Q

In reaction 5 of glycogenesis, after linear chain formation of about ____ molecules of glucose, the last ___/___ glucoses of the _____________ ends are detached and transferred onto a glucose closer to the __________ end, where the formation of an O-glycosidic (α1–>6) bond ties the glucose side branch to the linear branch.

A

11; 6/7; non-reducing; reducing

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17
Q

How many ATPs are needed to add each new glucose unit onto the glycogen molecule?

When?

A

Two ATPs!

1) Conversion of glucose into G6P (1 ATP)
2) UTP is used to transform G1P into UDP-glucose. One ATP equivalent is needed to convert UDP into UTP (1 ATP).

*Energy cost is high so glycogen synthesis is done right after a meal so ATP is not an issue! there is tons of glucose floating around used by glycolysis to produce lots of ATPs! ANYTHING COSTLY IS DONE RIGHT AFTER A MEAL.

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18
Q

What is a glycogen primer?

A

Short chain of glucose residues assembled linked to a small protein named GLYCOGENIN (37 kDa).

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19
Q

Match the terms to their definitions:

1) α-dextrin
2) maltose

A) two molecules of glucose linked by an o-glycosidic (α1–>4) bond.

B) mixtures of polymers of D-glucose units linked by (α1–>4) and (α1–>6) glycosidic bonds.

A

α-dextrin: mixtures of polymers of D-glucose units linked by (α1–>4) and (α1–>6) glycosidic bonds.

maltose: two molecules of glucose linked by an o-glycosidic (α1–>4) bond.

20
Q

Briefly describe how food glycogen/starch catabolism (glycogenolysis) occurs.

A

O-glycosidic (α1–>4) bonds are hydrolyzed by the α-AMYLASE from the saliva and pancreas.

Hydrolysis of the intra-chains results in the formation of maltose and α-dextrin.

α-dextrin is further hydrolyzed by α-DEXTRINASE which cleaves (α1–>6) bonds.

Removal of the branching point will be followed by another round of α-AMYLASE digestion.

Maltose is then hydrolyzed by MALTASE producing glucose which enters the blood stream.

21
Q

Match the steps of tissue glycogenolysis:

1) Step 1
2) Step 2
3) Step 3
4) Step 4
5) Step 5
6) Step 6

A) TRANSFER of 3 glucose molecules (trisaccharide) of the lateral chain to the nonreducing end of another chain, done by GLYCOGEN DEBRANCHING ENZYME’s (α1–>4) glycosyltransferase activity.

B) PHOSPHOROLYSIS of the remaining (α1 –>4) bonds. Done by GLYCOGEN PHOSPHORYLASE, producing multiple molecules of glucose-1-phosphate.

C) ISOMERIZATION of glucose-1-phosphate (G1P) to glucose-6-phosphate (G6P) by PHOSPHOGLUCOMUTASE.

D) O-glycosidic (α1–>4) bonds are broken by PHOSPHOROLYSIS done by PHOSPHORYLASE, generating Glucose-1-phosphate.

E) ONLY IN THE LIVER. HYDROLYSIS of G6P in glucose by GLUCOSE-6-PHOSPHATASE, which is then exported to the blood circulation.

F) HYDROLYSIS of the (α1–>6) bond, done by GLYCOGEN DEBRANCHING ENZYME’s (α1–>6) glucosidase activity. Produces one molecule of glucose per (α1–>6) bond.

A

Step 1: O-glycosidic (α1–>4) bonds are broken by PHOSPHOROLYSIS done by PHOSPHORYLASE, generating Glucose-1-phosphate.

Step 2: TRANSFER of 3 glucose molecules (trisaccharide) of the lateral chain to the nonreducing end of another chain, done by GLYCOGEN DEBRANCHING ENZYME’s (α1–>4) glycosyltransferase activity.

Step 3: HYDROLYSIS of the (α1–>6) bond, done by GLYCOGEN DEBRANCHING ENZYME’s (α1–>6) glucosidase activity. Produces one molecule of glucose per (α1–>6) bond.

Step 4: PHOSPHOROLYSIS of the remaining (α1 –>4) bonds. Done by GLYCOGEN PHOSPHORYLASE, producing multiple molecules of glucose-1-phosphate.

Step 5: ISOMERIZATION of glucose-1-phosphate (G1P) to glucose-6-phosphate (G6P) by PHOSPHOGLUCOMUTASE.

Step 6: ONLY IN THE LIVER. HYDROLYSIS of G6P in glucose by GLUCOSE-6-PHOSPHATASE, which is then exported to the blood circulation.

22
Q

When does reaction 1 of tissue glycogenolysis stop?

A

Reaction 1 (breaking of O-glycosidic (α1–>4) bonds by PHOSPHOROLYSIS) stops FOUR glucose units before a (α1–>6) branch.

23
Q

What happens to the glucose produced by glycogenolysis in the muscles vs in the liver?

A

In the muscle: Glucose is turned into Glucose-6-phosphate right away for glycolysis because the hexokinase has a low Km and is almost always active.

In the liver: Since the glucokinase has a high Km, little G6P is formed and most of the glucose is taken up by the blood of organ delivery instead of glycolysis.

24
Q

Why does the hydrolysis of G6P into glucose (Step 6 of tissue glycogenolysis) not occur in the muscles?

A

1) G6P is directly used in glycolysis in the muscles
2) Glucose-6-phosphatase (which does step 6) is absent in the muscles

25
Q

What is the von Gierke’s disease?

What happens? Where?

A

The von Gierke’s disease, which is also called Glycogen storage disease type I (GSD I), is characterized by a deficiency in glucose-6-phosphatase activity.

Abnormal accumulation of glycogen is observed in affected individuals. G6P in the LIVER can not be converted into glucose so it turns back to glycogen!

Not in the muscles b/c there is no glucose-6-phosphatase in the muscles.

26
Q

What diseases does glycogen storage disease type 1 (GSD I) cause? Why?

A

1) Hypoglycemia: no breakdown of glycogen to maintain blood glucose level

2) Lactic acidosis: impairment in GLUCONEOGENEIS. Accumulation of G6P blocks the conversion of lactate to pyruvate (an eventually to glucose).

27
Q

Which are the glycogen anabolism and metabolism limiting enzymes?

A

Glycogen synthesis: glycogen synthase
Glycogen breakdown: glycogen phosphorylase

28
Q

Glycogen synthase is subjected to two types of regulation _______ and ______.

It is ________ by dephosphorylation.

A

Allosteric; covalent

ACTIVATED

29
Q

What are the positive allosteric regulators of glycogen synthase?

A

G6P and Glucose!

They induce a conformational change that will favour dephosphorylation.

*rmbr glycogen synthesis only occurs after a meal, when there is high levels of glucose + insulin!

30
Q

Dephosphorylation (positive covalent regulation) of glycogen synthase is catalyzed by
__________ __________, which is activated in response to an increase in _________.

The insulin pathway will induce the phosphorylation of ______ _______ _______, which activates the catalyzing enzyme.

A

Phosphoprotein Phosphatase-1 (PP1); Glycemia (increased glucose + insulin)

Glycogen targeting protein (Gm)

31
Q

What is the negative regulation of glycogen synthase?

A

Covalent regulation:

1) Phosphorylation of Gm (2nd site) and inhibitor-1 by Protein Kinase A (PKA), leading to inactivation of Phosphoprotein Phosphatase-1 (PP1). PKA pathway is induced by the binding of GLUCAGON and ADRENALINE to their receptors.

2) Phosphorylation of glycogen synthase on THREE SITES by Glycogen Synthase Kinase 3 (GSK3). GSK3 is inhibited by insulin!

*PP1 dephosphorylates/activates glycogen synthase

32
Q

Glycogen phosphorylase is subjected to two types of regulation _______ and ______.

It is ________ by phosphorylation, which is done by ____________.

A

Allosteric; Covalent

Activated; Phosphorylase Kinase

33
Q

(T/F) PKA phosphorylates phosphorylase kinase which then phosphorylates glycogen phosphorylase!

A

True!

34
Q

What is the (+ and -) allosteric control of glycogen phosphorylase in the MUSCLE?

A

Positive: calcium + AMP
CALCIUM released by working muscles and AMP accumulation from muscle contraction activate glycogen breakdown by stimulating Phosphorylase B kinase.

Ca2+ acts on the phosphorylase kinase, while AMP binds to the phosphorylase itself.

Negative: ATP
ATP blocks the allosteric site to which AMP binds.

*muscle working a lot; need to make glucose
*if you have too much ATP, no need for glucose

35
Q

What is the covalent control of glycogen phosphorylase in the MUSCLE?

A

Epinephrine!

It stimulates glycogen breakdown by favouring phosphorylase phosphorylation through the PKA pathway.

36
Q

What is the covalent control of glycogen phosphorylase in the LIVER?

A

Glucagon!

Glucagon stimulates phosphorylase kinase to phosphorylate phosphorylase, activating glycogen breakdown.

Phosphorylation of the phosphorylase kinase is achieved via the PKA pathway.

*low glucose: glucagon

37
Q

How is the glycogen phosphorylase regulated in the LIVER at HIGH glucose conditions?

A

Allosteric control: GLUCOSE
- glucose binds to allosteric sites inhibiting phosphorylase by exposing its phosphorylation sites to PP1*, reducing glycogen breakdown!

Covalent control: INSULIN
- insulin stimulates PP1 to dephosphorylate the phosphorylase, inhibiting glycogen breakdown!

*PP1 removes the phosphates, rendering the phosphorylase inactive

38
Q

(T/F) Reciprocal regulation of glycogen metabolism contains glucagon on one end and insulin on the other. While insulin decreases glycogen breakdown and increases glycogen synthesis + glycolysis, glucagon increases glycogen breakdown and decreases glycogen synthesis + glycolysis.

A

True!

39
Q

(T/F) The Pentose Phosphate Pathway (PPP) is designed to produce energy.

A

False!

It can produce energy if it wants but it is not designed for that.

40
Q

What production does the PPP allow of?

A

1) NADPH: this coenzyme is necessary to certain synthesis reactions requiring reducing steps/reactions

2) Ribose-5-phosphate: sugar is essential to nucleic acid synthesis/co-enzymes.

41
Q

Where (5) is the PPP pathway mainly active in?

A

1) Liver: allows synthesis of fatty acids + cholesterol.

2) Adipose tissue: fatty acid synthesis

3) Mammary gland: fatty acid synthesis

4) Steroidogenic tissues: steroid hormone production

5) Red blood cells: repaid of oxidative damage

42
Q

(T/F) Activity of the PPP in the liver is equal to the activity of glycolysis.

A

False!

Activity of PPP in the liver is greater than that of glycolysis, since β-oxidation of lipids generates most of the energy in the liver.

43
Q

The starting substrate of PPP is ________________, which is generated by ____________ in the liver.

There are two phases of PPP: ________ and ___________.

A

Glucose-6-phosphate; hexokinase IV (glucokinase)

Oxidative (reduction of NADP+); non-oxidative

44
Q

Describe what happens in the Oxidative phase of PPP.

A

You start with Glucose-6-Phosphate (G6P) and then end with (1) Ribulose 5-phosphate/Ribose 5-Phosphate.

In this process you generate 2 NADPHs and lose one carbon!

45
Q

Describe what happens in the Non-oxidative phase of PPP.

A

Ribose 5-phosphate becomes nucleotides!

46
Q

What if we only want the NADPHs and not the nucleotides in a PPP?

A

In a closed loop, we make use of enzymes from Glycolysis/Gluconeogenesis and Transketolase, Transaldolase, Isomerase and Epimerase to make Ribose 5-phosphate into G6P!

47
Q

Match the four fates of G6P in the PPP according to cellular needs:

1) Cell needs BOTH ribose 5-phosphate/NADPH
2) Cell needs MORE NADPH than ribose 5-phosphate
3) Cell needs NAPDH and ATP
4) Cell needs ONLY ribose 5-phosphate

A) F6P and GAP from glycolysis is used to make ribose-5-phosphate in an INVERTED non-oxidative PPP.

B) Glyceraldehyde 3-phosphate (GAP) and Fructose 6-phosphate (F6P) generated by the non-oxidative phase of PPP is used to generate pyruvate.

C) Basic PPP

D) MORE NADPH than ribose 5-phosphate: In a closed loop, the enzymes from glycolysis and gluconeogenesis (+others) are recruited in the non-oxidative phase of PPP to convert ribose 5- phosphate into G6

A

Cell needs BOTH ribose 5-phosphate and NADPH: Basic PPP

Cell needs MORE NADPH than ribose 5-phosphate: In a closed loop, the enzymes from glycolysis and gluconeogenesis (+others) are recruited in the non-oxidative phase of PPP to convert ribose 5- phosphate into G6P.

Cell needs NAPDH and ATP: Glyceraldehyde 3-phosphate (GAP) and Fructose 6-phosphate (F6P) generated by the non-oxidative phase of PPP is used to generate pyruvate.

Cell needs ONLY ribose 5-phosphate: F6P and GAP from glycolysis is used to make ribose-5-phosphate in an INVERTED non-oxidative PPP.