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Biochem > Glucose metabolism > Flashcards

Glucose metabolism Flashcards

1
Q

Glucose is a good source of fuel. What are the 4 possible ways to use it?

A
  • STORAGE in the form of glycogen, starch, sucrose
  • OXIDATION VIA GLYCOSLYSIS to prode pyruvate
  • OXIDATION THROUGH PENTOSE PHOSPHATE PATHWAY to yield ribose-5-phosphate
  • SYNTHESIS OF STRUCTURAL POLYMER to yield extracellular matrix and cell wall polysaccharides
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2
Q

What are the 3 pathways of glucose utilization? Short description

A
  • Gluconeogenesis: Glucose is formed from a non-CHO source (from prots!)
  • Glycogenesis: Glycogen is polymerized from glucose units
  • Glycogenolysis: Glycogen is degraded to glucose units
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3
Q

What are the only 2 reversible steps in the first phase of the glycolysis ?

A

Step 2 (done by phosphohexose isomerase) and step 4 (done by aldolase)

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4
Q

What does aldolase cleave, and where?

A

Aldolase cleave between carbon 3 and 4 of fructose-1,6-phosphate

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5
Q

What type of phosphorylation in glycoslysis?

A

Substrate level phosphorylation

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6
Q

How can the cell overcome the gradient? If there is a need of glucose in the cell, a lot of glucose come in, glycolysis, how can there be more coming in?

A
  • The first step of adding a phosphate to create glucose-6-phosphate is crucial. It creates a change in glucose concentration and allow more glucose to come in
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7
Q

What is the yield vs net yield of glycolysis?

A

Yield: 4ATP+ 2NADH + 2 pyruvates

Net yield: 2 ATP + 2NADH + 2 pyruvates

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8
Q

Why is glycolysis highly regulated?

A

Because it ensures proper use of nutrients AND ensure production of ATP ONLY when needed

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9
Q

What are the 3 different fates of pyruvate? in what conditions?

A
  • Aerobic condition: Be converted to acetyl-CoA (production of CO2) and enter TCA cycle
  • Anaerobic condition: converted to lactate
    • fermented to lactate in contracting muscles, erythrocytes and other cells
  • Hypoxic or anaerobic conditions: fermented to ethanol (CO2 production) in yeast
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10
Q

What is the enzyme that converts glycogen and starch from diet into glucose?

A

a-Amylase!

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11
Q

Where is glucose cleave on glycogen? What enzymes does that ? What does it produce?

A

On the non-reducing end
Glycogen phosphorylase
Produces Glucose 1-phosphate

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12
Q

in gluconeogenesis, what are compounds that can be converted to glucose? (4)

A
  • Pyruvate
  • Glucogenic a.a.
  • Glycerol from TGs
  • 3-phosphoglycerate from carbon fixation
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13
Q

In glycolysis, what are the 3 enzymes that cannot do reverse action?

A

Hexokinase
Phospho-fructokinase-1
Pyruvate kinase

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14
Q

What are the enzymes that will do reverse action in gluconeogenesis?

A

Pyruvate carboxylase –> (oxaloacetate)–> Phosphoenolpyruvate carboxykinase

Fructose-1,6-bisphophatase 1

Glucose-6-phosphatase

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15
Q

What is used by pyruvate carboxylase to help bind pyruvate to bicarbonate to form oxaloacetate?

A

BIOTIN

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16
Q

What form of energy does pyruvate carboxykinase use?

A

GTP

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17
Q

What are the only a.a. that are not glucogenic?

A

Leucine and lysine

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18
Q

Can intermediate of TCA cycle enter gluconeogenesis?

A

Yes! all of them

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19
Q

When do we need NADPH?

A

FA synthesis in liver, kidney, cholesterol/steroid synthesis in liver etc.

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20
Q

What is an alternative pathway to Glucose-6-P? What is it used for?

A

Pentose phosphate pathway, proliferation and gene expression

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21
Q

Where/ what cells use pentose phosphate pathway? Where is it more common?

A
  • In cells that are highly proliferative
  • In cells that do FA biosynthesis
  • In cells that do cholesterol/sterol synthesis
  • Cells that have more oxidative stress(Red blood cells)
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22
Q

What does pentose phosphate pathway yield that is important against oxidative stress?

A

NADPH

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23
Q

How is Pentose phosphate pathway regulated?

A

Feedback inhibition: Production of NADPH when ribulose 5-phosphate is produce will inhibit the first production of NADPH ( at the step done by glucose-6-phosphate dehydrogenase)

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24
Q

What inhibits and activate PFK-1?

What inhibits FBPase-1?

A
  • Inhibits: ATP and citrate
  • Activates: AMP and ADP

FBPase is inhibited by AMP

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25
Q

If there is no oxygen, how is the NAD+ required for glycolysis produced ?

A

By converting pyruvate to lactate!

reversible reaction, lactate is reconverted to glucose in liver

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26
Q

Where can pyruvate be converted to oxaloacetate?

Where can oxaoacetate be converted to phosphoenolpyruvate?

A

Mitochondria

Mito/cytosol

27
Q

Where does gluconeogenesis mainly take place?

A

In liver

28
Q

Whre is hexokinase 4 more present?

A

IN LIVER!!!

29
Q

What hexokinase(s) are more present in muscles?

A

Hexokinase 1 and 2

30
Q

What is special about hexokinase 4?

A
  • it is not inhibited by glucose-6-phosphate–> continues to operate when accumulation of glucose-6-phosphate
  • It has higher saturation point than hexokinase 1 and 2
31
Q

What triggers inhibition of hexokinase 4 and when?

A

Fructose-6-phosphate (because it means there is gluconeogenesis, we don’t want to take up glucose, we want to release glucose in the blood!)

, during fasting

32
Q

What is the effect of F2,6P

A
  • It is an allosteric effector of PFK-1 and FBPase-1
  • Increase PFK-1 activity by binding allosterically to it
  • Deacreases FBPase-1 activity
33
Q

How does glucoagon affect concentration of F-2,6-P

A
  • GLucagon stimulates adenylyl cyclase of liver to synthesize 3-5-cyclic AMP. Cyclic AMP activates cAMP dependant prot which transfers P group from ATP to bifunctional PFK-2/FBPAse-2.

Phosphorylation of this prot enhance activity of FBPase-2 activity and inhibits its PFK-2 activity

SO glucagon thereby LOWERS F-2,6-P CONCENTRATION
and INHIBITS Glycolysis

34
Q

Where does Xylulose -5-phosphate comes from, and what does it do?

A
  • comes from pentose phosphate pathway.
  • X-5-p level rises as glucose level rises
  • INCREASE GLYCOLYSIS
35
Q

Where does glycogenesis take place?

A

In any cells, but mostly in liver

36
Q

What does glycogen first need to grow?

A

A sugar nucleotide

37
Q

What is the base in a sugar nucleotide?

A

Uridine (from RNA)

38
Q

What is the name of the enzyme that will create the first 8 glucose chain (1-4 glycosidic bound) ?

A

Glucogenin (has tyrosine on 194 residue)

Glucosyltransferase qill help make the 1-4 glycosidic bond

39
Q

What is an advantage of branching of glycogen?

A

Increases solubility, which is good because glycogen is stored as granule in the cytoplasm!

40
Q

What does glycogen phosphorylase do?

A

Does glycogenolysis: break down of glycogen to yield glucose-1-phosphate

41
Q

What does glycosyltransferase do?

A

Create 1-4 glycosidic bond in the initial short glucose chain formation

42
Q

What does glycogen synthase do?

A

Does elongation of glucose chain using UDP-glucose

43
Q

What are the type of enzymes involved in glycogenolysis?

A
  • GLycogen phosphorylase
  • Glycogen debranching enzyme
  • Phosphoglucose mutase
44
Q

On what does glycogen phosphorylase depend?

A

On pyridoxal phosphate cofactor

45
Q

What does glycogen debranching enzyme do?

A
  • Will remove the 3 glucose units before the glucose attached with 1-6 bond, and attach them to the non-reducing end of an existing longer chain ( debranching enzyme has glycosyl transferase activity)
  • It will finally remove the lonely glucose unit
46
Q

How is Glucose-1-phosphate transformed to glucose-6-phosphate? By which enzyme?

A

By Phosphoglucose mutase enzyme
- This enzymes needs to be phosphorylated to be active (first phosphorylated by ATP, but after, phosphate is recycled)

  1. Phophorylates glucose-1-phosphate on carbon 6
    - Becomes Glucose-1,6-bisphosphate
  2. Phosphate group on 1st carbon will be transfered on the serine residue of the enzyme, recycling the phosphate
47
Q

What are all the enzyme of glycolysis in order

A

-Go check notes and write it after

48
Q

Do muscle contribute to blood glucose concentration? Why?

A

NO, because muscles cannot express glucose-6-phosphatase to dephosphorylate glucose-6-phosphate to glucose and phosphate

49
Q

In muscles, what is the enzyme that cleaves glucose from glycogen called? Active and inactive form

Where is phosphorylation done and by what enzyme?

A

Active form: Phophorylase a (in contracting muscles)

Inactive form: Phosphorylase b (in resting muscles)

Phosphorylation is done on serines residues of the enzymes dimers, byt the enzyme phosphorylase a phosphatase

NEED OF ATP to phosphorylate!!!!

50
Q

What is the trick to know what enzyme is activated by phosphorylation or not?

A
  • Phosphorylase: phosphorylation activates

- Kinase: phosphorylation inactivates

51
Q

If glycogen synthase is phosphorylated it is in then in its _______ form

A

Desactivated form

52
Q

Aller voir slides 47-48 et faire dessin des pathways de insulin et glucagon

A

GO

53
Q

What inhibits PFK-1?

A

High ATP, high citrate

54
Q

What inhibits FBPase-1?

A

High AMP

55
Q

What other isomere of F-6-P activates PFK-1?

A

F-26-BP

56
Q

What activates pyruvate kinase L? Does phosphorylation activates or desactivates?

A

High ATP activates

Phosphorylation (because of glucagon) desactivates

57
Q

What inhibits pyruvate kinase L?

A

ATP, Acetyl-CoA, long chain fatty acids

Alanine (from transamination of pyruvate)

58
Q

When liver has enough FA for B-Oxidation, what happens to pyruvate?

A

Pyruvate is converted to oxaloacetate to enter gluconeogenesis, because there is a high concentration of Acetyl-Coa, which inhibits conversion of pyruvate to acetyl-CoA

59
Q

What does HIFI stands for?

A

hypoxia inducible factor 1

60
Q

What does HIF1 promote?

A

GLycolythic and pentose phosphate pathway because cancer cells are highly dependant of it

61
Q

What are the steps of glycogen synthesis, and what enzymes are involved?

A

Step 1: Formation of UDP-glycose (NDP-sugar pyrophosphorylase)
Step 2: Initial short chain synthesis (glycogenin)
Step 3: Elongation (Glycogen synthase)
Step 4: Branching ( glycogen branching enzyme)

62
Q

Where is glucose dephosphorylated when blood glucose is low? By what enzyme?

A

In ER of the liver by glucose-6-phosphatase

63
Q

When is phosphorylase the most active? What type is it then?

A

When it is phosphorylated. It is phosphorylase-a in contracting muscles

Biochem (8 decks)

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