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USMLE Biochemistry > Glycolysis > Flashcards

Glycolysis Flashcards

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
Q

What enzyme does insulin induce and what does this lead to?

A
  • 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
Q

What enzyme does glucagon induce and what does this lead to?

A
  • Fructose 2,6 bisphosphatase
  • Decreased F2,6 bisphosphate
  • Inhibits rate-limiting step (PFK1) and favors conversion of F1,6BP to F6P
27
Q

What are the 3 stages of glycolysis?

A
  • Priming stage (2ATP invested Glu-> F16BP)
  • Splitting (6 -> 3 Carbon structure)
  • Energy stage (ATP and pyruvate generated)
28
Q

What happens in the splitting stage of glycolysis?

A

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
Q

What does the enrgy stage of glycolysis start with?

A

Glyceraldehyde-3-phosphate (GAP)

30
Q

How many ATP are generated per GAP?

A

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
Q

What is the final reaction in the energy stage of glycolysis?

A

Phosphoenolpyruvate
- Pyruvate kinase (enzyme)
Pyruvate

  • 1 ATP produced
  • Irreversible

Phosphate group transferred from Phosphoenolpyruvate to ADP to create ATP

32
Q

What is the final stage of glycolysis inhibited by?

A
  • ATP
  • Alanine
  • Glucagon/epinephrine
33
Q

What is the final stage of glycolysis activated by?

A

F 1,6 BP

- Feed forward activation

34
Q

How can glucagon and epinephrine inhibit the final stage of glycolysis?

A

Through phosphorylation of pyruvate kinase

- Slows glycolysis and favors gluconeogenesis

35
Q

Why is alanine an inhibitor of the final stage of glycolysis?

A
  • 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
Q

What is pyruvate converted to to start the TCA cycle?

A

Acetyl-coA

37
Q

What enzyme converts pyruvate to Lactate?

A

Lactate dehydrogenase (LDH)

38
Q

When will LDH be raised in plasma?

A
  • Hemolysis
  • MI
  • Some tumors
39
Q

What can a high LDH in pleural fluid indicate?

A

Exudate (often a ratio to serum used to determine whether the fluid is exudate)

40
Q

How can NAD+ be generated in low O2 states?

A

Pyruvate -> Lactate generates NAD+ from NADH (allows the body to continue glycolysis)

  • If O2 present NADH may be converted to NAD in mitochondria
41
Q

What can increased anaerobic respiration lead to?

A
  • Elevated anion gap acidosis

- Decreased HCO3-, Decreased pH - Lactic acidosis

42
Q

What can cause lactic acidosis?

A
  • Sepsis
  • Bowel ischemia
  • Seizures
43
Q

What is the NADH to NAD ratio after exercise?

How may this be linked to cramps?

A

Elevated NADh/NAD ratio

  • Pyruvate -> lactate to generate more NAD
  • pH falls in muscles -> cramps
44
Q

How is pyruvate kinase deficiency inherited?

A

Aut recessive

45
Q

What cells are most affected by Pyruvate kinase deficiency? and why?

A

RBCs

  • No mitochondria
  • Require PK for anaerobic metabolism
  • Loss of ATP
  • Membrane failure -> phagocytosis in spleen
46
Q

When/How does PK deficiency usually present?

A

Newborn

  • Extravascular hemolysis
  • Splenomegaly
  • Severity ranges
47
Q

What is 2,3 bisphosphoglycerate created from?

A

1,3-bisphosphoglycerate by BPG Mutase

  • Diverts molecules away from glycolysis
  • Sacrifices ATP from glycolysis
  • Alters hemoglobin binding
48
Q

How many ATP are generated from glucose if O2 and mitochondria present?

A

30 ATP = malate-aspartate shuttle

32 ATP = glycerol-3-phosphate shuttle

49
Q

Write out the chemical formula for cellular aerobic respiration

A

Glu + 6O2 -> 32/30ATP + 6O2 + 6H2O

50
Q

Write out the formula for anaerobic respiration?

A

Glu -> 2ATP + 2Lactate + 2H2O

51
Q

What are the 3 places where glycolysis can be regulated?

A

The 3 irreversible steps:

Hexokinase/Glucokinase
- Glu -> G6P

PFK1
- F6P -> F-1,6-BP

Pyruvate Kinase
- Phosphoenolpyruvate -> Pyruvate

52
Q

What are the 2 satges where ATP is extended?

A

Glu -> G6P (hexo/glucokinase)

F-6-P -> F-1,6-P
PFK1

53
Q

Where are the 2 areas where ATP is generated?

A

1,3-bisphosphoglycerate -> 3-phosphoglycerate

Phosphoenolpyruvate -> Pyruvate

USMLE Biochemistry (44 decks)

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