Notes on Glycolysis

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What is Glycolysis?

• Glycolysis is the process by which glucose is converted via fructose-1,6-bisphosphate to pyruvate with the generation of 2 mol ATP per mol of glucose.

• There are a total of 10 enzymatic reactions involved in this pathway.

• Generates 2 ATP molecules, a source of energy for short burst needs only.

• Winemaking and bread baking both exploit this process.

• This pathway supplies fuel to the brain.

• This is an anaerobic pathway.

• The enzymes of glycolysis are located in the cytosol, where they are only loosely associated, if at all, with cell structures such as membranes.

3 Steps of Glycolysis:

1. Add phosphoryl groups to the glucose.

2. Chemically convert phosphorylated intermediates into compounds with high phosphate group-transfer potentials.

3. Chemically couple the subsequent hydrolysis of reactive substances to ATP systhesis.

2 Stages of Glycolysis:

Glycolysis Reactions 1-5:

A preparatory stage in which the hexose glucose is phosphorylated and cleaved to yield 2 molecules of triose glyceraldehyde-3-phosphate. This process uses two ATPs in a kind of energy investment.

Glycolysis Reactions 6-10:

The molecules of glyceraldehyde-3-phosphate are converted to pyruvate, with concomitant generation of four ATPs per glucose. Stage A consumes 2 ATPs, stage B produces 4 ATPs.

Overall Glycolysis Reaction:

Glucose + 2 NAD+ + 2 ADP + 2 Pi ----> 2 NADH + 2 pyruvate + 2 ATP + 2H2O + 4H+

From the above equation, it is obvious that 2NAD+ is a necessary ingredient required in glycolysis. There are 2 ways to generate NAD+:

1. Under aerobic conditions, the mitochondrial oxidation of each NADH to NAD+ yields three ATPs.

2. Under anaerobic conditions, NAD+ is regenerated when NADH reduces pyruvate to lactate.

Glycolysis Pathway Diagram

glycolysis pathway diagram

Summary of the Reactions of Glycolysis:

1. Hexokinase:

First ATP Utilization: This involves the transfer of a phosphoryl group from ATP to glucose to form glucose-6-phosphate in a reaction catalyzed by hexokinase.

2. Phosphoglucose Isomerase:

This involves the conversion of G6P to fructose-6-phosphate by phosphoglucose isomerase.

3. Phosphofructokinase:

Second ATP Utilization: Phosphofructokinase phosphorylates fructose-6-phosphate to yield fructose-1,6-bisphosphate.

4. Aldolase

Catalyzes the cleavage of fructose-1,6-bisphosphate to form two trioses glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP).

5. Triose Phosphate Isomerase:

In this step, interconversion of GAP and DHAP (isomerization of DHAP) occurs with the help of Triose Phosphate Isomerase.

6. Glyceraldehyde-3-Phosphate Dehydrogenase:

First "High-Energy" Intermediate Formation: This reaction involves the oxidation and phosphorylation of GAP by NAD+ and Pi, as catalyzed by Glyceraldehyde-3-Phosphate Dehydrogenase.

7. Phosphoglycerate Kinase:

First ATP generation: This reaction results in the first formation of ATP together with 3-phosphoglycerate from 1,3-bisphosphyglycerate in a reaction catalyzed by phosphoglycerate kinase.

8. Phosphoglycerate Mutase:

3-phosphoglycerate is converted to 2-phosphoglycerate by Phosphoglycerate Mutase.

9. Enolase:

Second High-Energy Intermediate Formation: 2-phosphoglycerate is dehydrated to phosphoenolpyruvate in a reaction catalyzed by enolase.

10. Pyruvate Kinase:

Second ATP Generation: Pyruvate kinase couples the free energy of phosphoenolpyruvate hydrolysis to the synthesis of ATP to form pyruvate.

Is phosphohistidine formed as an intermediate in glycolysis? Why is this compound important?

• Phosphohistidine is contained within enzyme phosphoglycerate mutase, which catalyzes reaction 8 of glycolysis.

Name the inhibitors of glycolysis and their sites of action:

Inhibitor Enzyme Glycolysis Step
Glucose-6-phosphate Hexokinase 1
ATP, Citrate, phosphoenolpyruvate Phosphofructokinase 3
ATP, fructose-1,6-bisphosphate, acetyl-CoA Phosphokinase 10

Additional Readings:

Basic Biochemistry

1. Nucleic Acid Structure and Organization
2. DNA Replication and Repair
3. Transcription and RNA Processing
4. Genetic Code, Mutations, and Translation
5. Genetic Regulation
6. Recombinant DNA
7. Amino Acids, Proteins, Enzymes
8. Hormones
9. Vitamins
10. Energy Metabolism
11. Glycolysis and Pyruvate Dehydrogenase
12. Citric Acid Cycle and Oxidative Phosphorylation
13. Glycogen, Gluconeogenesis, and Hexose Monophosphate Shunt
14. Lipid Synthesis and Storage
15. Lipid Mobilization and Catabolism
16. Amino Acid Metabolism Disorders
17. Purine and Pyrimidine Metabolism
18. Electron Transport
19. Citric Acid Cycle and Glyoxylate Cycle
20. Glycolysis
21. Pyruvate Metabolism
22. Mitochondrial ATP formation
23. Gluconeogenesis
24. Glycogen Metabolism
25. Nitrogen Fixation (Metabolism) reactions, and Heme Metabolism
26. Amino Acid Metabolism
27. What is Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)?

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