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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
PFK-1 Regulation and AMP
AMP is a heteroallosteric activator
26
PFK-1 Regulation and PEP
PEP is a heteroallosteric inhibitor
27
Pyruvate Kinase Regulation
Allosteric enzyme inhibited by ATP (product inhibition) Activated by fructose-1,6-bisphosphate (feed-forward activation)
28
Effect of F-1,6-BP on Pyruvate Kinase
Heteroallosteric activator | Feed forward activation
29
Effect of F-1,6-BP on Pyruvate Kinase Graph
Check cheat sheet
30
ATP as an Inhibitor
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
Glycogen Metabolism
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
Why is an anaerobic fate for pyruvate required?
To regenerate NAD+ for the oxidation reaction in glycolysis under anaerobic conditions
33
Glycolysis Produces:
2 pyruvate 2 NADH Net of 2 ATP
34
Why does NADH need to be reoxidized to NAD+?
``` For glycolysis to continue Aerobic -oxidative phosphorylation Anaerobic -pyruvate reduction (ethanol, lactate) ```
35
Production of Lactate
NOT an acid A dead-end product in skeletal muscle (during anaerobic activity) Pyruvate converted to lactate via lactate dehydrogenase
36
Lactate Production Equation
Pyruvate + NADH + H+ = L-Lactate
37
Lactate Exportation from the Muscle
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
Production of Ethanol
Does not occur in vertebrates Occurs in yeast -decarboxylation and reduction -final products = CO2, ethanol and NAD+
39
Pyruvate Dehydrogenase Reaction
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
What occurs in the matrix?
Pyruvate dehydrogenase Citric acid cycle Oxidative phosphorylation beta-oxidation (fatty acids)
41
Transport of Pyruvate
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
How is pyruvate converted to acetyl-CoA
Via the pyruvate dehydrogenase complex (PDC)
43
Pyruvate Dehydrogenase Reaction
Pyruvate + HS-CoA + NAD+ = Acetyl-CoA + CoA + CO2 + NADH
44
What is Acetyl-CoA?
Acetyl group attached via a thioester bond | -high energy molecule
45
Is the formation of Acetyl-CoA reversible?
No, the formation of acetyl-CoA is a key irreversible step in carbohydrate metabolism
46
More on the Pyruvate Dehydrogenase Reaction
``` Oxidative decarboxylation Transacetylation Irreversible Catalyzed by PDH -requires 5 cofactors including NAD+, FAD, CoA ```
47
Pyruvate Dehydrogenase Complex
Multienzyme complex that contains - multiple copies of three catalytic enzymes (decarboylate, transfer to CoA and oxidation) - 5 cofactors - regulated by kinases and phosphatases
48
Advantages of Multienzyme Complexes
Speeds up reaction times Limits number of side reactions Enzymes controlled as a single unit
49
Regulation of PDH
``` 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
How NAD+/NADH Ratio Regulates PDH
Substrate/product effect NADH inhibits PDH -allostery (inhibitor) -protein kinase activation (phosphorylation of PDH)
51
Acetyl-CoA and PDH Regulation
Inhibitor | Protein kinase activation (phosphorylation of PDH)
52
Ca++ and PDH Regulation
Protein phosphatase activation | -dephosphorylation of PDH
53
How is PDH Regulated by Reversible Phosphorylation
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
Inhibition of PDH
NADH and acetyl-CoA
55
Activation of PDH
NAD+ and HS-CoA

BIOCH 200 (9 decks)

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