Glycolysis and the Krebs Cycle: A Detailed Breakdown

Posted on Jan 15, 2025 in Biochemistry

Glycolysis

Glycolysis is the first step in cellular respiration. It is the process of breaking down glucose to make pyruvate. Glycolysis does not require oxygen (O2) and occurs in the cytosol.

Aerobic Respiration (Presence of Oxygen)

  • Glycolysis
  • Pyruvate oxidation, Krebs cycle
  • Electron transport chain (ETC), oxidative phosphorylation

Anaerobic Respiration (Absence of Oxygen)

  • Glycolysis
  • Alcoholic fermentation (yeast)
  • Lactic acid fermentation

Glycolysis Summary

  • Glucose is broken down into 2 pyruvate molecules.
  • Net 2 ATP molecules are produced (2 used, 4 generated).
  • 2 NADH molecules are produced.
  • Occurs in the cytoplasm.
  • Requires 2 ATP to start the process and produces 4 ATP.

Energy Investment Phase

In this phase, 2 ATP molecules form an unstable sugar with two phosphate groups, which then splits to form two three-carbon molecules that are isomers of each other.

Step 1

A phosphate group is transferred from ATP to glucose, forming glucose-6-phosphate (hexokinase). This is a phosphorylation reaction and requires energy.

Step 2

Glucose-6-phosphate is converted into its isomer, fructose-6-phosphate. The atoms are rearranged (isomerization, equilibrium) by phosphoglucose isomerase.

Step 3

A phosphate group is transferred from ATP to fructose-6-phosphate, forming fructose-1,6-bisphosphate. This reaction is catalyzed by the enzyme phosphofructokinase and requires energy.

Step 4

The unstable fructose-1,6-bisphosphate molecule splits to form two three-carbon sugars: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (aldolase).

Step 5

Only glyceraldehyde-3-phosphate (G3P) can continue through the next steps.

Energy Payoff Phase

Step 6

G3P is converted to 1,3-bisphosphoglycerate through a redox and phosphorylation reaction. NADH is created as NAD+ is reduced to NADH and H+. Triose phosphate dehydrogenase transfers electrons from G3P to NAD+ to form NADH. It uses the energy from this exergonic transfer of electrons to add a phosphate from the cytosol to the oxidized G3P, forming 1,3-bisphosphoglycerate.

Step 7

ADP is phosphorylated to create ATP. 1,3-bisphosphoglycerate is converted to 3-phosphoglycerate by kinase.

Step 8

3-phosphoglycerate is converted to 2-phosphoglycerate. The phosphate group moves from carbon 3 to carbon 2 (isomerase).

Step 9

2-phosphoglycerate loses water, forming phosphoenolpyruvate (PEP) (enolase).

Step 10

PEP is converted to pyruvate. ADP is phosphorylated to form ATP.

Krebs Cycle

The end product of glycolysis, pyruvate, must make its way into the mitochondrial matrix.

Pyruvate Oxidation (Oxidative Decarboxylation)

  1. Decarboxylation: The carboxyl group is removed, releasing CO2.
  2. Redox reaction: NAD+ is reduced to NADH.
  3. Coenzyme A addition: The acetyl group is transferred to coenzyme A, resulting in acetyl-CoA.

Pyruvate (3-carbon) is converted into acetyl-CoA (2-carbon) in order to be brought into the mitochondria.

Coenzyme A

  • Large organic molecule
  • Active functional group is a thiol
  • Also written as CoA-SH

Pyruvate Oxidation Summary

  • 2 pyruvate molecules are converted to 2 acetyl-CoA molecules.
  • 2 CO2 molecules are released.
  • 2 NADH molecules are produced.

The Krebs cycle generates more high-energy molecules (NADH, FADH2, ATP) and produces additional byproducts (CO2).

For Each Turn of the Krebs Cycle

  • 2 carbons are released as CO2.
  • 3 NADH and 1 FADH2 are formed.
  • 1 ATP is made by substrate-level phosphorylation.

Step 1

A 2-carbon molecule (acetyl-CoA) joins with a 4-carbon molecule (oxaloacetate) to form citrate (6-carbon). CoA is recycled.

Step 2

Atoms are rearranged with the help of H2O. Citrate is isomerized by aconitase into isocitrate.

Step 3

Synthesis of CO2 and NADH. The 6-carbon molecule is converted to a 5-carbon molecule. Isocitrate is oxidized into alpha-ketoglutarate by isocitrate dehydrogenase.

Step 4

Synthesis of CO2 and NADH (reduced). The 5-carbon molecule is converted to a 4-carbon molecule. CoA returns. Alpha-ketoglutarate is converted into succinyl-CoA by alpha-ketoglutarate dehydrogenase.

Step 5

ADP is phosphorylated to form ATP. CoA is recycled. Succinyl-CoA is converted into succinate by succinyl-CoA synthase.

Step 6

FADH2 formation. Succinate is converted into fumarate by succinate dehydrogenase.

FAD/FADH2

  • FAD: Flavin adenine dinucleotide (oxidized form)
  • FADH2: Flavin adenine dinucleotide (reduced form)

FAD/FADH2 works similarly to NAD+/NADH, accepting electrons.

Step 7

The molecule is rearranged for the next reaction. Fumarate is converted into malate by fumarase.

Step 8

Energy molecule formation and recreating molecules for the Krebs cycle. Malate is converted into oxaloacetate by malate dehydrogenase.

Krebs Cycle Summary

  • Per cycle: 2 CO2, 3 NADH, 1 FADH2, and 1 ATP are produced.
  • There are two cycles of the Krebs cycle for each glucose molecule.