Glycolysis Flashcards

1
Q

Glycolysis

A
Anaerobic pathway for ATP generation 
-ancient 
-conserved
-can operate aerobically 
10 enzyme-catalyzed reactions occur in cytosol 
One glucose is broken down to 2 pyruvate
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2
Q

Stage 1 of Glycolysis

A

Energy Investment

  • glucose needs to be activated
  • ATP is consumed
  • involves hexose sugars
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3
Q

Stage 2 of Glycolysis

A

Energy Payout

  • energy is harvested in the form of ATP
  • NADH is also generated
  • involves triose sugars
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4
Q

Glucose -> Glucose 6-Phosphate

A
ATP investment
Irreversible 
Coupled reaction 
Phosphate transfer
Catalyzed by hexokinase
Regulated but not rate limiting
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5
Q

Glucose 6-Phosphate -> Fructose 6-Phosphate

A

Isomerization

Reversible

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6
Q

Fructose 6-Phosphate -> Fructose 1,6-bisphosphate

A
ATP investment 
Coupled reaction 
Phosphate transfer 
Catalyzed by phosphofructokinase-1
Regulated and rate limiting
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7
Q

Fructose 1,6-bisphosphate -> GAP

A

Lysis

Reversible

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8
Q

Fructose 1.6-bisphosphate -> DHAP -> GAP

A

Isomerization
Reversible
Second molecule of GAP produced via a different pathway

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9
Q

One molecule of Glucose Produces Two Molecules of GAP

A

Every reaction described from GAP to pyruvate happens twice per glucose

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10
Q

GAP -> 1,3 bisphosphoglycerate

A

Oxidation
Reversible
Energy Capture (NADH)
Catalyzed by GAPDH

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11
Q

1,3-BPG

A

High energy intermediate
-acyl phosphate
-stabilized by resonance
large phosphate-transfer potential

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12
Q

1,3-Bisphosphoglycerate -> 3-Phosphoglycerate

A
Substrate-level phosphorylation
Reversible
Coupled (ATP synthesis)
Energy capture step (ATP)
Phosphate transfer
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13
Q

3-Phosphoglycerate -> 2-Phosphoglycerate

A

Isomerization

Reversible

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14
Q

2-Phosphoglycerate -> Phosphoenolpyruvate (PEP)

A

Dehydration

Reversible

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15
Q

PEP

A

High energy intermediate

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16
Q

PEP -> Pyruvate

A
Substrate-level phosphorylation 
Irreversible 
Coupled (ATP synthesis)
Catalyzed by pyruvate kinase (regulated)
Energy capture step (ATP)
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17
Q

Overall Glycolysis Reaction

A

Glucose + 2 ADP + 2 NAD+ + 2 Pi = 2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O

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18
Q

Net ATP production per glucose

A

2 ATP

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19
Q

Why is Glycolysis Regulated

A

Ensures that energy needs are met

Glucose is not wasted when ATP is abundant

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20
Q

Means of Regulation in Glycolysis

A
Substrate availability 
-glucose import
Enzyme Regulation
-hexokinase
-phosphofructokinase-1 (rate-limiting)
-pyruvate kinase
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21
Q

Hexokinase Inhibition

A

G6P acts as a negative allosteric effector for hexokinase

Product Inhibition

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22
Q

PFK-1 Regulation

A

Allosterically regulated by ADP/AMP and PEP
If there is more ADP/AMP than ATP, then the cell needs more ATP
Elevated PEP indicates that the products of glycolysis are not being consumed
Feedback Inhibition

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23
Q

PFK-1 Regulation Graph

A

Check cheat sheet

24
Q

PFK-1 Regulation and FGP

A

FGP is a homoallosteric activator

25
Q

PFK-1 Regulation and AMP

A

AMP is a heteroallosteric activator

26
Q

PFK-1 Regulation and PEP

A

PEP is a heteroallosteric inhibitor

27
Q

Pyruvate Kinase Regulation

A

Allosteric enzyme
inhibited by ATP (product inhibition)
Activated by fructose-1,6-bisphosphate (feed-forward activation)

28
Q

Effect of F-1,6-BP on Pyruvate Kinase

A

Heteroallosteric activator

Feed forward activation

29
Q

Effect of F-1,6-BP on Pyruvate Kinase Graph

A

Check cheat sheet

30
Q

ATP as an Inhibitor

A

PFK-1 and PK are both inhibited by ATP

  • most enzymes catalyze reversible reactions
  • synchronous regulation of reversible reactions
  • maintain steady-state for intermediates
31
Q

Glycogen Metabolism

A

Glycogen is synthesized from glucose-6-phosphate (anabolic)
Breakdown of glycogen uses inorganic phosphate to break glycosidic bonds
When we start from glycogen, we get more ATP/glucose (3) because no ATP is used to generate G-6-P from glycogen

32
Q

Why is an anaerobic fate for pyruvate required?

A

To regenerate NAD+ for the oxidation reaction in glycolysis under anaerobic conditions

33
Q

Glycolysis Produces:

A

2 pyruvate
2 NADH
Net of 2 ATP

34
Q

Why does NADH need to be reoxidized to NAD+?

A
For glycolysis to continue
Aerobic
-oxidative phosphorylation
Anaerobic
-pyruvate reduction (ethanol, lactate)
35
Q

Production of Lactate

A

NOT an acid
A dead-end product in skeletal muscle (during anaerobic activity)
Pyruvate converted to lactate via lactate dehydrogenase

36
Q

Lactate Production Equation

A

Pyruvate + NADH + H+ = L-Lactate

37
Q

Lactate Exportation from the Muscle

A

Lactate and protons are exported from the muscle to the blood via a specific membrane transporter protein

  • lowers pH
  • encourages O2 release from hemoglobin = the Bohr effect
38
Q

Production of Ethanol

A

Does not occur in vertebrates
Occurs in yeast
-decarboxylation and reduction
-final products = CO2, ethanol and NAD+

39
Q

Pyruvate Dehydrogenase Reaction

A

Catalyzed by pyruvate dehydrogenase complex
-PDH, PDC
Links glycolysis to the citric acid cycle
-connects the two processes, part of neither
Occurs inside the mitochondria, in the matrix

40
Q

What occurs in the matrix?

A

Pyruvate dehydrogenase
Citric acid cycle
Oxidative phosphorylation
beta-oxidation (fatty acids)

41
Q

Transport of Pyruvate

A

Glycolysis generates pyruvate in the cytosol
Pyruvate is converted to acetyl-CoA in the mitochondrial matrix
Transport across the inner mitochondrial membrane requires the transporter protein pyruvate translocase
A proton is transported with the pyruvate

42
Q

How is pyruvate converted to acetyl-CoA

A

Via the pyruvate dehydrogenase complex (PDC)

43
Q

Pyruvate Dehydrogenase Reaction

A

Pyruvate + HS-CoA + NAD+ = Acetyl-CoA + CoA + CO2 + NADH

44
Q

What is Acetyl-CoA?

A

Acetyl group attached via a thioester bond

-high energy molecule

45
Q

Is the formation of Acetyl-CoA reversible?

A

No, the formation of acetyl-CoA is a key irreversible step in carbohydrate metabolism

46
Q

More on the Pyruvate Dehydrogenase Reaction

A
Oxidative decarboxylation
Transacetylation
Irreversible
Catalyzed by PDH
-requires 5 cofactors including NAD+, FAD, CoA
47
Q

Pyruvate Dehydrogenase Complex

A

Multienzyme complex that contains

  • multiple copies of three catalytic enzymes (decarboylate, transfer to CoA and oxidation)
  • 5 cofactors
  • regulated by kinases and phosphatases
48
Q

Advantages of Multienzyme Complexes

A

Speeds up reaction times
Limits number of side reactions
Enzymes controlled as a single unit

49
Q

Regulation of PDH

A
Highly regulated
Irreversible Reaction 
-Acetyl-CoA cannot be used to make glucose
Sensitive to ATP requirements
Regulated by:
NAD+/NADH ratio
Ca++ concentration
Acetyl-CoA
50
Q

How NAD+/NADH Ratio Regulates PDH

A

Substrate/product effect
NADH inhibits PDH
-allostery (inhibitor)
-protein kinase activation (phosphorylation of PDH)

51
Q

Acetyl-CoA and PDH Regulation

A

Inhibitor

Protein kinase activation (phosphorylation of PDH)

52
Q

Ca++ and PDH Regulation

A

Protein phosphatase activation

-dephosphorylation of PDH

53
Q

How is PDH Regulated by Reversible Phosphorylation

A

Switched off when energy levels are high
Phosphorylation (via a kinase) switches off the activity of the complex (inactive)
-protein kinase is activated by NADH + Acetyl-CoA
Dephosphorylation (via phosphatase) activates the complex (active)
-protein phosphate activated by Ca++

54
Q

Inhibition of PDH

A

NADH and acetyl-CoA

55
Q

Activation of PDH

A

NAD+ and HS-CoA