Lecture 7 Concepts

Anomeric Rings Formation

• Glucose (Aldose) and Fructose (Ketose): Both sugars can form cyclic structures due to their carbonyl groups.

  • Glucose: When the carbonyl group (aldehyde) reacts with an alcohol group (on carbon 5), it forms a six-membered ring called a pyranose

  • Fructose: The ketone group reacts with an alcohol group (on carbon 2), leading to a five-membered ring called a furanose.

• The ring size is influenced by whether the sugar is an aldehyde (glucose) or ketone (fructose).

General Layout of Glycolytic Pathway

• Glycolysis consists of two main phases:

  1. Preparatory Phase:

  • Consumes ATP to phosphorylate glucose and intermediates.

  • Key steps include conversion of glucose to fructose 1,6-bisphosphate.

  1. Payoff Phase:

  • Generates ATP and NADH through the conversion of 1,3-bisphosphoglycerate to pyruvate.

  • Important components are regenerated, ensuring continuous flow of glucose metabolism.

Source of ATP in Glycolysis

- ATP is generated through substrate-level phosphorylation, primarily in the payoff phase.

• Net Gain of ATP:

  • Two ATP are consumed in the preparatory phase; four ATP are produced in the payoff phase.

  • This results in a net gain of two ATP molecules for the cell (4 produced - 2 consumed).

Structures of Metabolites and Reactions of Glycolysis

• Glycolysis comprises 11 reactions leading from glucose to pyruvate (including lactate dehydrogenase).

• Key metabolites include:

  1. Glucose

  2. Glucose-6-phosphate

  3. Fructose-6-phosphate

  4. Fructose-1,6-bisphosphate

  5. Dihydroxyacetone phosphate

  6. Glyceraldehyde-3-phosphate

  7. 1,3-Bisphosphoglycerate

  8. 3-Phosphoglycerate

  9. 2-Phosphoglycerate

  10. Phosphoenolpyruvate

  11. Pyruvate

Enzymes of Glycolysis

• Key enzymes include:

  • Hexokinase: Phosphorylates glucose, trapping it in the cell.

  • Phosphofructokinase (PFK): Regulatory enzyme for fructose 6-phosphate phosphorylation.

  • Aldolase: Splits fructose-1,6-bisphosphate into two triose sugars.

  • Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH): Converts G3P into 1,3-bisphosphoglycerate while generating NADH.

  • Pyruvate Kinase: Catalyzes the final step of glycolysis.

GAPDH Mechanism

• The GAPDH mechanism involves converting G3P to 1,3-bisphosphoglycerate.

• The reaction facilitates the addition of an inorganic phosphate to G3P without utilizing ATP.

• NAD+ is reduced to NADH in this process, critical for the energy yield in glycolysis.

The glycolytic pathway comprises 11 reactions leading from glucose to pyruvate, including lactate dehydrogenase (LDH). Here are the reactions in sequence:

1. Glucose to Glucose-6-phosphate: Catalyzed by Hexokinase, glucose is phosphorylated using ATP.

2. Glucose-6-phosphate to Fructose-6-phosphate: This reaction is catalyzed by Phosphoglucose isomerase.

3. Fructose-6-phosphate to Fructose-1,6-bisphosphate: Catalyzed by Phosphofructokinase (PFK), another ATP is used for phosphorylation.

4. Fructose-1,6-bisphosphate to Dihydroxyacetone phosphate and Glyceraldehyde-3-phosphate: Split by Aldolase into two triose sugars.

5. Dihydroxyacetone phosphate to Glyceraldehyde-3-phosphate: This conversion is catalyzed by Triose phosphate isomerase.

6. Glyceraldehyde-3-phosphate to 1,3-Bisphosphoglycerate: Catalyzed by Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH), NAD+ is reduced to NADH, and an inorganic phosphate is added.

7. 1,3-Bisphosphoglycerate to 3-Phosphoglycerate: This conversion generates ATP via substrate-level phosphorylation, catalyzed by Phosphoglycerate kinase.

8. 3-Phosphoglycerate to 2-Phosphoglycerate: Catalyzed by Phosphoglycerate mutase.

9. 2-Phosphoglycerate to Phosphoenolpyruvate: This dehydration reaction is catalyzed by Enolase.

10. Phosphoenolpyruvate to Pyruvate: Catalyzed by Pyruvate kinase, another ATP is produced via substrate-level phosphorylation.

11. Pyruvate to Lactate: In the absence of oxygen or during anaerobic conditions, lactate is formed catalyzed by Lactate dehydrogenase (LDH), with NADH being oxidized back to NAD+.