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Metabolic Pathways > Glycolysis > Flashcards

Glycolysis Flashcards

1
Q

What is the storage form of glucose?

A

Glycogen

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2
Q

What type of pathway is the citric acid pathway?

A

Catabolic

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3
Q

What is the first stage of catabolism in the presence of oxygen?

A

In glucose, fatty acids and amino acids (least 10) all converge to make simple 2C Acetyl-CoA

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4
Q

What metabolite feeds into the citric acid cycle?

A

Acetyl-CoA

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5
Q

What is an example of a sugar that is a major fuel for most organisms and has a central position in metabolism?

A

D-Glucose

- Major source of metabolic energy in brain, erythrocytes, renal medulla, sperm.

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6
Q

Complete oxidation of one D-glucose gives what after the 3 stages of catabolism?

A

CO2, H2O and gives mega-energy: DeltaG’0 = -2840kJ/mol

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7
Q

What is the major source of energy in the brain?

A

D-glucose.

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8
Q

What does E.coli rely on for energy and biomolecular synthesis?

A

D-glucose

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9
Q

What is the product of oxidation of glucose via glycolysis?

A

Pyruvate.

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10
Q

What pathway is responsible for the largest flux of C in cells?

A

Glycolysis

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11
Q

How many enzymes are used in the glycolysis of D-glucose to pyruvate?

A

10

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12
Q

What do the 10 enzymes in glycolysis allow for?

A

They allow for specific thermodynamically favourable molecular processes that keep all cells alive.

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13
Q

Is glycolysis regulated?

A

Highly regulated and is only catabolized with cells need energy.

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14
Q

What cells rely on glucose as a major source of energy?

A

Sperm, erythrocytes, brain, renal medulla

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15
Q

What can E.coli synthesis from glucose?

A

C skeletons for every amino acid, nucleotide, coenzyme, fatty acid and other intermediates it needs for growth and function from glucose.

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16
Q

What diseases have altered glycolysis?

A

Diabetes, cancer, neurodegeneration, infection and more.

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17
Q

What are the major pathways of glucose utilization?

A
  • synthesis of structural polymers
  • storage
  • oxidation via glycolysis
  • oxidation via pentose phosphate pathway.
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18
Q

How was glycolysis discovered?

A

It was the first metabolic pathway elucidated in yeast and muscle cells.

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19
Q

How many carbons does pyruvate have?

A

3C

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20
Q

What biochemical processes in the cell were discovered as a result of studies on glycolysis?

A

The role of ATP and phosphorylates compounds in cell biology discovered by research which discovered glycolysis.

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21
Q

How does elevated glucose levels affect SARS-Cov-1 infection?

A

Diabetes - elevated glucose favor SARS-Cov-1 infection and monocyte response through a glycolysis dependent axis.

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22
Q

What is the first enzyme in the prep phase (P.1). Glucose is phosphorylated on pos.6.
What donates a phosphate?

A

Hexokinase - ATP donates a phosphate
It is a regulatory enzyme.
The phosphorylation of glucose by HK ‘traps’ glucose inside cells for metabolism.

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23
Q

What are kinases?

A

These are a large family that add phosphoryl groups to substrates.
Mostly need magnesium

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24
Q

Describe the hexokinase induced fit?

A

Has a U-shaped clamp like structure.

Conformational change induced by binding of D-glucose.

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25
Q

Irreversible enzymes are often?

A

Regulatory

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26
Q

What is the second enzyme in the prep phase which isomerize glucose 6 - phosphate to fructose 6-phosphate.

A

Phosphohexose Isomerase (PHI)

  • reversible reaction (aldose to ketose)
  • small change in standard free energy
  • shuffles atoms to move carbonyl from C1 to C2
  • His residue in active site of enzyme opens ring structure to achieve this.
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27
Q

What does phosphohexose isomerase (PHI) do?

A

Glucose 6-phosphate isomerized to fructose 6-phosphate.

28
Q

What is the 3rd enzyme in the prep phase which phosphorylated fructose?

A

Phosphofructokinase-1 (PFK-1)

Bacterial form has 4 subunits, human form can be more complex

29
Q

What does phosphofructokinase-1 do?

‘committed step’ - highly regulated

A

Phosphorylates fructose 6- phosphate to fructose 1-6- bisphosphate (2 phosphates either end)

  • priming irreversible reaction.
  • major regulatory enzyme for glycolysis
  • decided time is right to be o/off
30
Q

What is the 4th enzyme in the prep phase of glycolysis?

A

Enzyme Aldolase - hexose is split to form two trioses = 2 x3C sugar phosphates.
- reversible
- near-equilibrium
produces DHAP and GAP -3

31
Q

What is the 5th enzyme in the prep phase of glycolysis?

A

Triose phosphate isomerase (TPI)

32
Q

What does triose phosphate isomerase (TPI) do?

A

It isomerases DHAP to GAP-3, maintains a steady state

  • near equilibrium reaction
  • TPI ‘pulls’ a H off one carbon and replaces it on another carbon
  • perfect enzyme
  • speeds isomerisation 1 billion times faster than that would happen.
33
Q

What is the main energy molecule that goes on in glycolysis after the prepatory phase?

A

Glyceraldehyde 3-phosphate.

34
Q

What are the 5th and 6th step/enzyme of glycolysis, in the pay off phase?

A

Glyceraldehyde 3- phosphate dehydrogenase (removal of electrons to an acceptor NAD)2x

35
Q

What is the 6th step glyceraldehyde 3-phosphate dehydrogenase?

A

Oxidation (loss) + phosphorylation.

36
Q

What donates energy in step 6?

A

An inorganic phosphate, on the glyceraldehyde 3- phosphate.

37
Q

What is the oxidation equation in step 6?

A

oxidation transfers electrons from 2XG3P to 2NAD

38
Q

What is the final product of step 6 in the pay off phase?

A

1,-3 bisphosphate - has a very high energy of hydrolysis = -49kJ/mol.
This molecule gives energy to produce 2ATP X2 in reaction 7 &8

39
Q

What is the enzyme in step 7?

A

Phosphoglycerate kinase

40
Q

What happens at step 7?

A

1,-3 phosphoglycerate is dephosphorylated at pos 1 to yield 2x3-phosphoglycerate & 2ATP.
- induced fit (2 lobes))

41
Q

Which two enzymes in glycolysis have an induced fit?

A

Hexokinase

Phosphoglycerate kinase

42
Q

What do steps 8 and 9 consist of?

A

Moving things around to make them more favourable for donating the final phosphate to an ATP in the last reaction

43
Q

What is the enzyme in step 8?

A

Phosphoglucomutase - reversible

changing from 2x3 phosphoglycerate to 2x2 phosphoglycerate

44
Q

What is the enzyme in step 9?

A

Enolase - the 2x2 phosphoglycerate is dehydrated to yield 2 x phosphoenolpyruvate and 2xH2O
= puts phosphate in uncomfortable reaction to encourage it to move.
- high energy

45
Q

What is the 10th enzyme?

A

Pyruvate kinase (4 flexible subunits)
2x phosphoenolpyruvate to dephosphorylated to yield 2x pyruvate & 2ATP.
- irreversible
- 2nd substrate level phosphorylation (like 7)
- allosteric - can be turned on/off, senses

46
Q

What are the 3 sensory enzymes?

Regulatory enzymes

A

phosphofructokinase (3)
hexokinase (1)
Pyruvate kinase (10)

47
Q

What is the standard free energy available after glycolysis? (anaerobic)

A

-85kj/mol - pyruvate contains most of the chemical potential energy of glucose extracted in aerobic conditions in stage 2/3 catabolism.

48
Q

Where does glycolysis occur in the cell?

A

Cytosol

49
Q

What is the difference between the 2 phases in terms of energy?

A

Prep - 2ATP produced

Pay off - 4 ATP and 2NADH produced.

50
Q

Where is NADH produced in glycolysis and how?

A

In step 6 - when oxidation involves the transfer of electrons from 2- F3P to 2NAD –> 2NADH = energy

51
Q

What is a substrate level phosphorylation?

A

The phosphate comes from a substrate onto ATP rather than be made by ATP synthase in the mitochondria.

52
Q

What is the overall energy equation?

A

glucose + 2 NAD+ + 2ADP +2pi —-> 2 pyruvate + 2NADH+ +2TP + 2H20

53
Q

What are the 3 fates of pyruvate in the presence and absence of O2?

A

Anaerobic : Ethanol (x2 + 2CO2) or lactate (2x)

Aerobic: 2 Acetyl Co-A (stage 2 and 3 of catabolism ) - more energy rich

54
Q

When oxygen happens where does the product cycle of

glycolysis occur?

A

In the mitochondria.
Decarboxylation occurs on the pyruvate to make the 2 acetyl CoA and the 2CO2.
For one glucose = ~2850kj energy produced for aerobic oxidation.

55
Q

What are the 2 fates of pyruvate in the absence of oxygen?

A
  • reduced to lactate (lactate dehydrogenase)
  • reduced to ethanol (alcohol dehydrogenase)
  • produces 5% of energy (85kh/mkl compared to aerobic.
56
Q

Which produces more energy aerobic or anaerobic ?

A

Aerobic: 2850kj energy
Anaerobic:85kj energy.

57
Q

Why is the anaerobic phase of glycolysis important?

A

As it keeps recycling rapidly to produce 2ATP per glucose & to regenerate essential NAD+ for step 6 of glycolysis.

58
Q

is pyruvate decarboxylase present in vertebrates ?

A

It is absent and lactic acid bacteria so impossible to convert pyruvate to ethanol.

59
Q

When is lactate produced in the body from pyruvate?

A
  • erythroblasts, retina, brain cells produce lactate when O2 present, responsible for at least 10% of overall glucose breakdown.
  • very active skeletal muscle uses anaerobic pyruvate - lactic acid
  • cancer cells and immune cells can have very active aerobic glucose catabolism even in the presence of O2.
60
Q

Where is lactate produced?

A

Made from broken down muscle glycogen stores - > glucose -> pyruvate -> lactate for energy
Lactate is produced in the blood -> liver
Lactate synthesised in liver glucose goes from liver -> blood -> muscle replenished glycogen.

61
Q

Who discovered the role of anaerobic glycolysis and cancer?

A

Discovered by Otto Warburg in the 20s
Cancerous cells/tissues can have very active anaerobic glucose catabolism to lactate even in the presence of O2.
This is due to ‘re-wiring’ of glycolysis and metabolism to allow energy production to maximize proliferation.

62
Q

What and why is a PET scan used in cancer patients?

A

Used as levels of many glycolytic enzymes increase and use different isoforms of certain glycolytic enzymes occurs.
2F-Deoxyglucose is used - shows ip the glucose intake in cancer cells and the increased glycolysis and glucose metabolism in cancer cells.

63
Q

What types of enzymes are increased in cancer cells?

A

Glycolytic enzymes
Different isoforms of these enzymes can occur including
- Pyruvate kinase PKM2 rather than PKM1
- PKM” has a reduced cat activity
- This allows cancer cells to keep using anaerobic glycolysis.
Uses as a two way system, cat and ana. Can promote proliferation.

64
Q

How does anaerobic glycolysis affect the cells of the immune system?

A

Immune cells ‘rewire’ metabolism to use aerobic glycolysis: Glucose —> Lactate even when O2 is present.
Hijack the system to produce more cytokines.
They use the glucose - pyruvate - lactate.
Glycolytic switch can be good and bad (inflammation - cytokine storm) regulation = immunometabolism

65
Q

Is pyruvate oxidised or reduced when it is converted to lactate/ethanol?

A

Reduced

66
Q

Does NAD+ get regenerated for step 6 of glycolysis in the conversion of pyruvate -> lactate and ethanol?

A

Yes it does

Metabolic Pathways (13 decks)

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