Glycolysis Flashcards

1
Q

What is glycolysis ?

A

A key pathway in preparing glucose (and other CHO) for oxidative degradation.

A series of reactions.

Glycolysis - sugar splitting

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2
Q

What happens in glycolysis ?

Transport of glucose

A

Blood glucose is transported into cells (e.g. Glut2 and Glut4 - enhanced by insulin), lowering blood concentrations.

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3
Q

Where does glycolysis take place ?

A

In the cytosol of the cell

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4
Q

Describe some fates of glucose within the cell

A

Glycolysis
Glycogen
Fat

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5
Q

Glycolysis

A

Catabolism

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6
Q

Glycogen

A

Anabolism

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7
Q

Fat

A

Anabolism

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8
Q

What is the aim of glycolysis ?

A

One molecule of glucose is converted into 2 molecules of pyruvate.

Pyruvate is then converted into acetyl co-enzyme A, which enters the Citric Acid Cycle.

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9
Q

State the stages of Glycolysis

A

Investment
Cleavage
Energy Harvest

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10
Q

How much energy is required for glycolysis ?

A

2 ATP are required for early reactions

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11
Q

State the net yield of ATP generated by glycolysis

A

4 ATP are generated later, giving a NET YIELD of :

2 ATP per glucose

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12
Q

How many carbon molecules are in pyruvate and glucose ?

A

Pyruvate - 3
Glucose - 6

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13
Q

Describe the 2 fates of pyruvate produced from glycolysis

A

In AEROBIC conditions :

  • pyruvate enters the citric acid cycle
  • converted to acetyl-co-enzyme A

IN ANAEROBIC (low oxygen) conditions :

  • Lactate is formed from pyruvate (fermentation)
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14
Q

State the strategy for the glycolysis pathway

A
  1. Add phosphoryl groups to glucose and intermediates
  2. Chemically convert phosphorylated intermediates to compounds with high energy phosphate bond potential.
  3. Chemically couple the hydrolysis of reactive compounds to generate ATP (and NADH+ and H+)
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15
Q

Describe step 1 of Glycolysis

A

Phosphorylation of glucose at carbon 6

Requires ATP (INVESTMENT STAGE)

Locks glucose inside the cell
(maintains glucose gradient)

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16
Q

Describe step 2 of Glycolysis

A

Conversion of glucose-6-P to fructose-6-P

G-6-P ring structure opens to enable isomerisation and subsequent ring closure. F-6-P

(G-6-P : Glucose 6 phosphate)

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17
Q

Describe step 3 of Glycolysis

A

Fructose 6 phosphate is phosphorylated at carbon 1, and becomes fructose 1,6-biphosphate (FBP)

Requires ATP (INVESTMENT phase)

Phosphofructokinase (PFK) key regulatory point

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18
Q

Describe step 4 of Glycolysis

A

Aldolase cleaves the FBP into 2x trioses

Glyceraldehyde-3-phosphate (GAP)
Dihydroxyacetone phosphate (DHAP)

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19
Q

Describe step 5 of Glycolysis

A

DHAP is readily converted into GAP

2 GAPs for every glucose molecule.

Glyceraldehyde-3-phosphate (GAP)
Dihydroxyacetone phosphate (DHAP)

20
Q

Describe step 6 of Glycolysis

A

Oxidation and Phosphorylation of GAP by NAD+ and Pi

First ‘high energy’ intermediate-aldehyde oxidation (exergonic reaction)

This drives the synthesis of the 1-3 bisphosphoglycerate

21
Q

Describe step 7 of Glycolysis

A

First formation of ATP (energy harvest)

The newly formed high-energy phosphate bond used to synthesise ATP and 3-phosphoglycerate (3PG)

22
Q

Describe step 8 of Glycolysis

A

3PG converted to 2PG

This is essential preparation for the next energy harvest step.

23
Q

Describe step 9 of Glycolysis

A

2PG dehydration to form phosphoenolpyruvate (PEP)

Converts low energy phosphate ester bond of 2PG into high-energy intermediate phosphate bond

24
Q

Describe step 10 of Glycolysis

A

Hydrolysis of PEP high-energy bond generates ATP and pyruvate.

This is a physiological irreversible reaction

e.g. of substrate level phosphorylation

25
Q

Describe the energy yield from glycolysis

A

Glycolysis releases relatively little energy from glucose - the majority is released during the final stage, electron transfer chain and oxidative phosphorylation.

26
Q

What happens to pyruvate under anaerobic conditions ?

A

Converted to lactate

27
Q

What happens to pyruvate under aerobic conditions ?

A

Pyruvate is transported to the mitochondrial matrix and converted to acetyl-coenzyme A, which feeds into the citric acid cycle.

NADH+ and H+ are oxidised to replenish NAD+ via the electron transport chain.

When cellular energy levels (ATP) in excess, acetyl-coenzyme A used for synthesis of fatty acids.

28
Q

What happens to pyruvate under high cellular energy levels ?

A

Fatty acids or ketone bodies

29
Q

Describe lactate production in anaerobic conditions

A

For glycolysis to continue in anaerobic conditions, NAD+ must be replenished.

When ATP demand is high and oxygen is depleted, homolactic fermentation regenerates NAD+

Reversible reaction which enables glycolysis to continue for short amounts of time.

The build up of lactate causes muscle cramps and limits activity.

Slow/fast twitch myofibre composition determines the rate of muscle fatigue.

30
Q

What type of reaction is the production of lactate ?

A

A redox reaction

Oxidisation of NADH into NAD
Reduction of pyruvate into lactate

A highly exergonic reaction

31
Q

Describe the structure of lactate dehydrogenase

A

Composed of 2 different types of subunit : H or M

5 isozymes - Tissue specific expression

Tetrameric - different combinations of subunits combine

32
Q

What does the presence of lactate dehydrogenase in the blood indicate ?

A

Gives an indication of where in the body damage has occurred.

33
Q

What does tetrameric mean ?

A

Different combinations of subunit combine.

34
Q

Describe lactate dehydrogenase in aerobic conditions

A

LDHB gene –> subunit H
Chromosome 12
H subunits found in the heart tissue

35
Q

Describe lactate dehydrogenase in anaerobic conditions

A

LDHA gene –> subunit M
Chromosome 11
M subunits found in muscle tissue

36
Q

State the use of lactate dehydrogenase in diagnosis

A

Differing properties and tissue locations

Damage to specific tissues releases cell contents into circulation.

Changes in serum levels - aids disease diagnosis

37
Q

Where is LDH 1 found ?

A

Predominantly / only found in cardiac tissue (also RBCs and kidneys)

Elevated in myocardial infarction

Fastest moving

38
Q

Where is LDH 5 found ?

A

Skeletal muscle, Liver

Elevated in skeletal muscle and liver diseases

Slowest moving

39
Q

State ways in which the rate of glycolysis is controlled

A

Key enzymes

High ATP inhibit enzyme activity

Intermediate substrates (e.g. fructose-6-P) stimulate PFK activity

High citric acid inhibits

Low pH inhibits

Hormones

40
Q

State the key regulatory enzymes involved in glycolysis

A

Hexokinase

PFK

Pyruvate kinase

41
Q

Function of hexokinase

A

Locking glucose into the cell

42
Q

Describe hexokinase

What is it inhibited by ?

A

Allosterically inhibited by G-6-P

43
Q

Describe phosphofructokinase

What is it activated and inhibited by ?

A

Most IMPORTANT site of control

  • first step unique to glycolysis

High [ATP] inhibits PFK : allosterically bind a region separate from the active site

High [AMP] activates PFK (2ADP –> ATP + AMP)

44
Q

Function of phosphofructokinase

A

1st step unique to glycolysis

45
Q

Describe pyruvate kinase

What is it activated and inhibited by ?

A

Inhibited by high ATP and alanine and activated by FBP

46
Q

Function of pyruvate kinase

A

Last step from high energy compound into pyruvate