Glycolysis-12 Flashcards

1
Q

What is Glycolysis?

A

Breakdown of glucose by series of connected reactions

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2
Q

What is the purpose of Glycolysis?

A
  1. The making of energy carrying molecules such as ATP
  2. The making of pyruvate, the end product in glycolysis, to continue further in downstream metabolic pathways (i.e citric acid)
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3
Q

Glycolysis

A

The pathway of Glycolysis occurs in the cytoplasm of the cell

Once pyruvate is generated (the end product of glycolysis) it will be converted into

With oxygen,
Go through aerobic oxidation,
product is Acetyl-CoA, 
Acetyl-CoA go through the citric acid, 
products of Acetyl-CoA go onto the electron transport chain and then oxidative phosphorylation 

Without oxygen,
Go through Anaerobic alcoholic fermentation,
Carbon Dioxide and Ethanol

If there isn’t enough oxygen,
Anaerobic homolactic fermentation occurs
we will form lactic acid

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4
Q

What are the Fates of Glucose?

A

Glucose can either be stored as glycogen, starch or sucrose

  1. Go through oxidation via glycolysis to form Pyruvate
  2. Go through oxidation via pentose phosphate pathway to form Ribose-5-phosphate
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5
Q

You need oxygen for Glycolysis to happen True/False

A

False

Glycolysis can occur with or without oxygen

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6
Q

Nerve cell and glucose

A

Nerve cells in the brain rely predominantly on glucose as an energy source

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7
Q

What are the 2 stages of Glycolysis Metabolism?

A

1.) Glycolysis

  1. ) a.) Fermentation
    - occurs in the absence of O2 in the cytoplasm
    - partial breakdown of glucose

OR

b. ) Cellular Respiration
- occurs in the presence of O2 in the mitochondria
- complete breakdown of glucose

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8
Q

Glycolysis Metabolism under anaerobic and aerobic conditions:

A

Under anaerobic conditions (in the absence of O2) pyruvate is converted by a process known as fermentation, into lactate or ethanol in the cytoplasm

Under aerobic conditions, it may enter the mitochondria where it will be oxidized in the presence of O2 to become CO2 and H2O

Generating an additional 30-34 ATP molecules
-Cellular respiration

Cellular respiration consists of 2 path ways

  1. Krebs cycle
  2. Oxidative Phosphorylation
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9
Q

What are the possible fates of pyruvate produced from glycolysis in the 2nd stage of glucose metabolism?

depending on the availability of O2

In Anaerobic conditions

A

Pyruvate is fermented in the cytoplasm to

  1. Alcohol
  2. Lactate
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10
Q

What are the 2 stages in cellular respiration?

A
  1. Krebs cycle (citric acid cycle)

2. Oxidative Phosphorylation

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11
Q

What are the possible fates of pyruvate produced from glycolysis in the 2nd stage of glucose metabolism?

depending on the availability of O2

In Aerobic conditions

A

Pyruvate enters the krebs cycle in the mitochondria and be oxidized in the presence of O2 to become CO2 or H2O

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12
Q

Definition of Glycolysis:

A

Glycolysis is a process whereby a glucose molecule is broken down in the absence of O2 (anaerobic respiration) into 2 pyruvate molecules, producing a net yield of 2 ATP molecules in the process

Occurs in the cytoplasm

O2 comes into the picture after glycolysis

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13
Q

What occurs in the first stage of glycolysis? How many reactions are there?

A

Stage 1 investment

1-5 reactions

It is a preparatory stage in which the hexose glucose is phosphorylated and cleaved to yield two molecules of the triose glyceraldehyde-3-phosphate. Stage 1 consumes 2 ATPs

Uses 2 ATPs in a kind of energy investment

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14
Q

What occurs in the second stage of glycolysis? How many reactions are there?

A

Harvest
reactions 6-10

The 2 molecules of glyceraldehyde-3-phosphate are converted to pyruvate, with concomitant generation of 4 ATPs, Stage 2 produces 4 ATPs. Glycolysis therefore has a net profit of 2 ATPs per glucose

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15
Q

Overall Glycolysis reaction summary

A

Glucose + 2NAD + 2ADP +2P –> 2NADH + 2 pyruvate +2 ATP+ 2H2O + 4H+

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16
Q

10 reactions of Glycolysis:

A
  1. Phosphorylation of glucose by ATP to make glucose 6-phosphate

2-3 Rearrangement by a second ATP phosphorylation

4-5 The six carbon molecule is split into two three-carbon molecules of G3P

  1. Oxidation followed by phosphorylation produces 2 NADH molecules and gives 2 molecules of BPG (1,3-biphosphoglycerate), each with one high-energy phosphate bond
  2. Removal of high-energy phosphate by 2 ADP molecules produces 2 ATP molecules and gives 2 3PG (3-phosphoglycerate) molecules

8-9 Removal of water gives 2 PEP molecules (phosphoenolpyruvate)

  1. Removal for high energy phosphate by 2 ADP molecules produces 2 ATP molecules and gives 2 pyruvate molecules

Glucose + 2NAD + 2ADP +2P –> 2NADH + 2 pyruvate +2 ATP+ 2H2O + 4H+

17
Q

How is the energy present in glucose harvested in glycolysis?

A

First energy investment
-2 ATP molecules is used to convert glucose to the highly reactive fructose-1, 6-bisphosphate

-Fructose-1, 6-biphosphate splits into 2 smaller molecules of glyceraldehyde-3-phosphate (G3P)

18
Q

What is the enzyme that catalyzes the 1st step of glycolysis?

A

Hexokinase enzyme
(transferase)

transfer of phosphate from ATP to glucose to make glucose-6-phosphate

There is a conformation change upon glucose binding

“closing” of two lobes draws the substrates glucose and ATP together

After the product glucose-6-phosphate is formed, the conformation goes back to starting state

19
Q

What are the enzymes and their products involved in the 10 reactions of Glycolysis? Investment and Harvest stages

A

Investment
1. Hexokinase
Function: Transfer of a phosphoryl group from ATP to glucose
Products: From glucose to Glucose-6-phosphate

  1. Glucose-6-phosphate isomerase
    Function: Isomerization (changing of the structure of the chemical)
    Products: Glucose-6-Phosphate to Fructuose-6-phosphate
  2. Phospho-fructose kinase
    Function: Transfer of a phosphoryl group from ATP to fructose 6-phosphate
    Products: Fructose-6-phosphate to Fructose 1,6 bisphosphate

4- Aldolase
Function: C-3-C-4 bond cleavage, yielding two triose phosphates
Products: Fructose 1,6 bisphosphate to Dihydroxy acetone phosphate and Glyceraldehyde 3 phosphate

5-Triose phosphate isomerase (rapidly Isomerized)
Function: Rapid interconversion of triose phosphates
Products: From Dihydroxyacetone Phosphate to Glyceraldehyde 3 phosphate (because Dihydroxyacetone phosphate cannot be readily degraded like Glyceraldehyde, not in the useable form)

6-Glyceraldehyde 3-phosphate dehydrogenase
Function: Oxidation and phosphorylation, yielding a high energy mixed-acid anhydride
Products: Glyceraldehyde 3 phosphate to 1,3-Bisphosphoglycerate

Harvest
7-Phosphoglycerate kinase
Function: Transfer of high energy phosphoryl group to ADP, yielding ATP (Made one ATP)
Products: 1,3-Bisphosphateglycerate to 3 Phosphoglycerate

8-Phosphoglycerate mutase
Function: Intramolecular phosphoryl-group transfer
Products: 3-phosphoglycerate to 2-phosphoglycerate

9-Enolase
Function: Dehydration to an energy-rich enol ester
Products: 2-Phosphoglycerate to Phosphoenolpyruvate

10- Pyruvate kinase
Function: Transfer of high energy phosphoryl group to ADP yielding ATP
Products: Phosphoenolpyruvate to pyruvate

20
Q

When in glycolysis does the reaction use up ATP?

A

During the investment stage

In the 1st reaction, when hexose kinase converts glucose into glucose-6-phosphate by transfer of a phosphoryl group from ATP to glucose

In the 3rd reaction, when Phospho-fructose kinase transfer a phosphoryl group from ATP to Fructose 6-phosphate to form Fructose 1,6 bisphosphate

21
Q

When in glycolysis does the reaction makes ATP?

A

During the Harvest stage

In the 7th reaction, when Phosphoglycerate kinase converts 1,3-Bisphosphoglycerate to 3-Phosphoglycerate. A phosphoryl group is transferred to ADP yielding ATP

In the 10th reaction, when Pyruvate kinase converts Phospho enoyl pyruvate to pyruvate .A phosphoryl group is transferred to ADP yielding ATP

22
Q

Function of Phosphoglucose isomerase (Glucose-6-phosphate isomerase):

A

During the 2nd step of glycolysis:
Glucose-6-phosphaye-> Fructose-6-phosphate

Molecular changes of glucose-6-phosphate in the active site of phosphoglucose isomerase

23
Q

How is the energy present in glucose harvested in glycolysis?

A

The 2 G3P molecules undergo a series of reactions that result in the generation of 4 ATP and 2 NADH
Therefore, glycolysis results in a net production of 2 ATP and 2 NADH per glucose molecules

24
Q

What is NADH?

A

Nicotinamide adenine dinucleotide hydride or also known as coenzyme 1 (NOT co enzyme A)

NADH is a co enzyme without which many enzymes are useless

25
Q

What is the significance of NAD+?

A

NAD+ (from the glyceraldehyde-3-phosphate dehydrogenase)

provides the oxidizing power for glycolysis to occur in the absence of O2.

As such, in order for glycolysis to occur continuously, NAD+ must be continuously be regenerated

  • in the presence of O2, NAD+ would be regenerated via oxidative phosphorylation (later part of cellular respiration)
  • in the absence of O2, NAD+ would be regenerated via fermentation
26
Q

Energy input and Energy output summary of the Glycolysis reaction:

A

Energy input:
2 ATP molecules

Energy output:
4 ATP molecules- net yield 2 ATP molecules
2 NADH molecules
Pyruvate molecules

27
Q

What is the purpose of glycolysis?

A

To produce ATP (e.g muscle contraction)

28
Q

Can ATP and AMP regulate glycolysis?

A
  • Too much ATP (energy-rich): INHIBIT glycolysis

- Too much AMP (energy-poor): ACTIVATE glycolysis

29
Q

What are the 3 regulatory points at the enzyme level?

Regulation of Glycolysis

A
  1. Hexokinase (HK)
  2. Phosphofructokinase-1 (PKJ)
  3. Pyruvate kinase (PK)
30
Q

What are the molecules that will inhibit or activate glycolysis?

A

Activate:

  • too much AMP
  • too much 2,6-fructose bisphosphate
  • too much 1,6-fructose bisphosphate

Inhibit:

  • too much ATP
  • too much citrate
  • too much Glucose-6-phosphate
  • No AMP
31
Q

Examples of other sugars that can enter the glycolytic pathway:

A

1- Fructose
2-Galactose
3-Mannose
4-Glycerol

(can be converted to an intermediate molecule in glycolysis)

32
Q

What are the diseases associated with the glycolysis pathway? Glycolysis defects

A

For patients with deficient levels of hexokinase and pyruvate kinase enzymes, the oxygen binding to their haemoglobin is altered

For hexokinase deficient cases, the O2 binding curve is shifted to the left of normal

That results in too tight association, so O2 cannot be sufficiently released

(bind too much to oxygen and very tightly, cannot release the oxygen from the red blood cell to the rest of the body)

For pyruvate kinase deficient cases, the O2 binding curve is shifted to the right of normal. That results in too loose association , so O2 cannot be sufficiently taken up

(bind too loosely, loose association, oxygen cannot be taken up efficiently)

33
Q

How does Hexokinase and pyruvate kinase deficiency lead to abnormal O2 haemoglobin binding?

A

2,3-bisphosphoglycerate (2,3-BPG) is the byproduct of the eight reaction in glycolysis

2,3-BPG directly binds to empty haemoglobin and inhibits O2 binding

Low hexokinase levels -> lower 2,3 BPG, so O2 binding to haemoglobin is raised
(the production of the products down the reaction will be stopped)

Low pyruvate kinase
-> Higher 2,3-BPG, O2 binding to haemoglobin is decreased because 2,3-BPG INHIBITS O2.

34
Q

What occurs during the cooperative binding of oxygen?

A

Uptake of oxygen by a heme subunit results in a shift in the deoxyhaemoglobin structure, and 2,3-DPG is expelled.

This structure change facilitates the binding of oxygen by the other 3 heme subunits

Binding of oxygen at one site in the haemoglobin tetramer influence the oxygen binding properties at the other sites

35
Q

What is 2,3 DPG (diphosphoglycerate) and its function/ importance?

A

2,3-DPG is the byproduct of glycolytic pathway (glycolysis) when ATPs are produced in RBCs.

-regulates the structure and function of haemoglobin

36
Q

What happens when there is too less 2,3-DPG and too much?

A

When 2,3-DPG is low (because hexokinase is deficient) then our haemoglobin binds oxygen too tightly and our tissues cannot get oxygen

Too high, 2,3-DPG is high (pyruvate kinase is deficient) then our haemogobin binds oxygen too loosely and cannot draw enough of it from the lungs

37
Q

How does 2,3-DPG change the structure of haemoglobin?

A

B-chain of haemoglobin move closer when oxygenated, 2,3-DPG is pushed out

B-chains are pulled apart when O2 is unloaded, permitting entry of 2,3-DPG resulting in lower affinity of O2