Glycolysis Flashcards

(53 cards)

1
Q

How many carbons does glucose and pyruvate contain?

A
  • Glucose - 6

- Pyruvate - 3

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2
Q

What is the function of NADH?

A

To carry electrons

  • NAD+ accepts electrons
  • NADH donates (can donate to ETC -> ATP)
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3
Q

What is the first reaction in glycolysis?

What enzyme is involved?

A

Glucose
-> Glucose-6-phosphate

Enzyme: Hexokinase (mostly) or Glucokinase

Consumes 1ATP

Irreversible

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4
Q

What do kinase enzymes add?

A

Phosphate (usually comes from ATP)

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5
Q

What inhibits the first reaction in glycolysis (Glucose -> G6P)?

A

Glucose-6-phosphate

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6
Q

What are the properties of Hexokinase?

A
  • Low Km (usually operates max)
  • Low Vmax (max is not that high)

Glucose concentration only needs to increase slightly and Hexokinase will be operating at its max

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7
Q

Where is glucokinase found?

A

Liver and pancreas

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8
Q

What are the significant differences between glucokinase and hexokinase?

A
  • Glucokinase not inhibited by G6P
  • Induced by insulin (hexokinase not)
  • Insulin promotes transcription
  • High Km and Vm
  • Inhibited by F6P (overcome by increased glucose)
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9
Q

What inhibits glucokinase?

When is the only time Glucokinase is inactive?

A

F6P (overcome by increased glucose)

  • Only inactive when low glucose and high F6P
  • I.e in times of fasting, low glucose, high conversion to F6P for gluconeogenesis
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10
Q

Describe the enzyme mechanics behind glucokinase?

A
  • High Vmax and Km

- Sigmoidal curve - cooperativity, activity varies with glucose

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11
Q

How does F6P inactivate glucokinase?

A

Activates GKRP which:

- Translocates glucokinase to nucleus - inactivating the enzyme

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12
Q

What protein translocates glucokinase to the nucleus?

A

Glucokinase Regulatory Protein (GKRP)

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13
Q

How do high levels of glucose cause glucokinase to become active?

A
  • Glucose competes with GKRP for glucokinase binding

- Stops GKRP from takinf Glucokinase into nucleus - remaining in cytosol and therefore remaining active

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14
Q

What enzymes are working at low blood sugar?

A
  • Hexokinase working (no inhibition of G6P)
  • Glucokinase inactive (rate alpha glucose; low insulin)
  • Glucose to tissues not liver
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15
Q

What enzymes are active/inactive in the presence of low blood sugar?

A
  • Hexokinase inactive (inhibited by G6P)
  • Glucokinase working (high glucose, high insulin)
  • Liver will store glucose as glycogen
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16
Q

How does glucokinase deficiency manifest?

A
  • Hyperglycemia
  • Pancreas less sensitive to glucose
  • Mild hyperglycemia
  • Often exacerbated by pregnancy
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17
Q

What is the rate limiting step of glycolysis?

What is the enzyme?

A

Fructose 6 phosphate
-> Fructose 1,6 phosphate

Enzyme: Phosphofructokinase-1

Consumes 1ATP

Irreversible

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18
Q

What stage in glycolysis commits glucose to glycolysis? (HMP shunt, glycogen synthesis no longer possible)

A

Fructose 6 phosphate
-> Fructose 1,6 phosphate

Enzyme: Phosphofructokinase-1

RATE LIMITING STEP

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19
Q

What inhibit phosphofructokinase-1 (rate limiting step)?

A

Indicate high energy level:

  • Citrate (TCA cycle)
  • ATP
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20
Q

What induce phosphofructokinase-1 (rate limiting step)?

A
  • AMP

- Insulin (fructose 2,6 bisphosphate), activates PFK1 , turns ON glycolysis

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21
Q

What enzyme reverses the rate limiting step of glycolysis?

A

Fructose 1,6 biphosphatase

Reaction:
Fructose-1,6-biphosphate
-> Fructose-6-phosphate

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22
Q

What enzyme converts F-2,6-bisphosphate to Fructose-6-phosphate?

23
Q

What enzyme converts Fructose-6-phosphate to F-2,6-bisphosphate?

A

Phosphofructokinase 2 (PFK2)

24
Q

What enzyme acts as an on off switch for glycolysis (activates PFK1, rate limiting step)?

A

F 2,6 bisphosphate

25
What enzyme does insulin induce and what does this lead to?
- Insulin induces PFK2 (converts F6P to F2,6BP) - Increased Frctose, 2, 6 bisphospahte then induces phosphofructokinase 1 to convert: - Fructose 6 phosphate to Fructose 1,6 bisphosphate
26
What enzyme does glucagon induce and what does this lead to?
- Fructose 2,6 bisphosphatase - Decreased F2,6 bisphosphate - Inhibits rate-limiting step (PFK1) and favors conversion of F1,6BP to F6P
27
What are the 3 stages of glycolysis?
- Priming stage (2ATP invested Glu-> F16BP) - Splitting (6 -> 3 Carbon structure) - Energy stage (ATP and pyruvate generated)
28
What happens in the splitting stage of glycolysis?
Fructose-1,6-bisphosphate is converted into: - 2 molecules of Glyceraldehyde-3-phosphate (GAP) - Some can be converted initially into Dihydroxyacetone phosphate and then converted to GAP - All reactions reversible
29
What does the enrgy stage of glycolysis start with?
Glyceraldehyde-3-phosphate (GAP)
30
How many ATP are generated per GAP?
2 per GAP - 4 overall (as 2 GAP generated from F16BP/Glu) - Overall in glycolysis 2 ATP generated (as 2 lost in Priming stage)
31
What is the final reaction in the energy stage of glycolysis?
Phosphoenolpyruvate - Pyruvate kinase (enzyme) Pyruvate - 1 ATP produced - Irreversible Phosphate group transferred from Phosphoenolpyruvate to ADP to create ATP
32
What is the final stage of glycolysis inhibited by?
- ATP - Alanine - Glucagon/epinephrine
33
What is the final stage of glycolysis activated by?
F 1,6 BP | - Feed forward activation
34
How can glucagon and epinephrine inhibit the final stage of glycolysis?
Through phosphorylation of pyruvate kinase | - Slows glycolysis and favors gluconeogenesis
35
Why is alanine an inhibitor of the final stage of glycolysis?
- Represent a lack of glucose throughout the body - Skeletal muscles can degrade protein for energy - Byproduct of degradation is alanine - Alanine inhibits pyruvate kinase - Liver converts alanine to glucose via gluconeogenesis
36
What is pyruvate converted to to start the TCA cycle?
Acetyl-coA
37
What enzyme converts pyruvate to Lactate?
Lactate dehydrogenase (LDH)
38
When will LDH be raised in plasma?
- Hemolysis - MI - Some tumors
39
What can a high LDH in pleural fluid indicate?
Exudate (often a ratio to serum used to determine whether the fluid is exudate)
40
How can NAD+ be generated in low O2 states?
Pyruvate -> Lactate generates NAD+ from NADH (allows the body to continue glycolysis) - If O2 present NADH may be converted to NAD in mitochondria
41
What can increased anaerobic respiration lead to?
- Elevated anion gap acidosis | - Decreased HCO3-, Decreased pH - Lactic acidosis
42
What can cause lactic acidosis?
- Sepsis - Bowel ischemia - Seizures
43
What is the NADH to NAD ratio after exercise? How may this be linked to cramps?
Elevated NADh/NAD ratio - Pyruvate -> lactate to generate more NAD - pH falls in muscles -> cramps
44
How is pyruvate kinase deficiency inherited?
Aut recessive
45
What cells are most affected by Pyruvate kinase deficiency? and why?
RBCs - No mitochondria - Require PK for anaerobic metabolism - Loss of ATP - Membrane failure -> phagocytosis in spleen
46
When/How does PK deficiency usually present?
Newborn - Extravascular hemolysis - Splenomegaly - Severity ranges
47
What is 2,3 bisphosphoglycerate created from?
1,3-bisphosphoglycerate by BPG Mutase - Diverts molecules away from glycolysis - Sacrifices ATP from glycolysis - Alters hemoglobin binding
48
How many ATP are generated from glucose if O2 and mitochondria present?
30 ATP = malate-aspartate shuttle 32 ATP = glycerol-3-phosphate shuttle
49
Write out the chemical formula for cellular aerobic respiration
Glu + 6O2 -> 32/30ATP + 6O2 + 6H2O
50
Write out the formula for anaerobic respiration?
Glu -> 2ATP + 2Lactate + 2H2O
51
What are the 3 places where glycolysis can be regulated?
The 3 irreversible steps: Hexokinase/Glucokinase - Glu -> G6P PFK1 - F6P -> F-1,6-BP Pyruvate Kinase - Phosphoenolpyruvate -> Pyruvate
52
What are the 2 satges where ATP is extended?
Glu -> G6P (hexo/glucokinase) | F-6-P -> F-1,6-P PFK1
53
Where are the 2 areas where ATP is generated?
1,3-bisphosphoglycerate -> 3-phosphoglycerate Phosphoenolpyruvate -> Pyruvate