Glycolysis and the citric acid cycle are key players in cellular energy production. They break down glucose and other nutrients, generating ATP and important molecules for various cellular processes.

These pathways work together to extract energy from food. Glycolysis happens in the cell's cytoplasm, while the citric acid cycle occurs in mitochondria. Understanding their steps is crucial for grasping how cells power themselves.

Glycolysis

Overview of Glycolysis

• Glycolysis is a metabolic pathway that breaks down glucose into two pyruvate molecules
• Occurs in the cytoplasm of cells and does not require oxygen (anaerobic)
• Net production of 2 ATP and 2 NADH molecules per glucose molecule
• Consists of two phases: the preparatory phase and the payoff phase
• Key enzymes involved include hexokinase, phosphofructokinase, and pyruvate kinase

Energy and Electron Carriers in Glycolysis

• ATP (adenosine triphosphate) is the primary energy currency of the cell
  • Used to drive energy-requiring reactions in glycolysis (phosphorylation of glucose and fructose-6-phosphate)
  • Net production of 2 ATP per glucose molecule through substrate-level phosphorylation
• NADH (reduced nicotinamide adenine dinucleotide) is an electron carrier
  • Produced during the oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate
  • Carries electrons to the electron transport chain for further ATP production

Fate of Pyruvate

• Pyruvate is the end product of glycolysis
• Under aerobic conditions, pyruvate enters the mitochondria for further oxidation in the citric acid cycle
• Under anaerobic conditions, pyruvate can be reduced to lactate (in animals) or ethanol (in yeast and plants)
• Pyruvate is a key metabolic intermediate that links glycolysis to other pathways (citric acid cycle, gluconeogenesis, and amino acid synthesis)

Pyruvate Oxidation

Conversion of Pyruvate to Acetyl-CoA

• Pyruvate is transported into the mitochondrial matrix
• Undergoes oxidative decarboxylation catalyzed by the pyruvate dehydrogenase complex
• Loses a carbon dioxide molecule (decarboxylation) and is oxidized to form acetyl-CoA
• This irreversible reaction links glycolysis to the citric acid cycle

Electron Transfer and NADH Production

• During oxidative decarboxylation, electrons are transferred from pyruvate to NAD+, forming NADH
• NADH carries the electrons to the electron transport chain for ATP production through oxidative phosphorylation
• This step is crucial for generating reducing equivalents (NADH) to drive ATP synthesis

Citric Acid Cycle

Overview of the Citric Acid Cycle

• Also known as the Krebs cycle or tricarboxylic acid (TCA) cycle
• Occurs in the mitochondrial matrix and is a central metabolic hub
• Oxidizes acetyl-CoA derived from carbohydrates, fats, and proteins
• Generates high-energy electron carriers (NADH and FADH2) and GTP (or ATP)
• Produces precursors for amino acid and heme synthesis (α-ketoglutarate, succinyl-CoA)

Acetyl-CoA as the Entry Point

• Acetyl-CoA, produced from pyruvate oxidation, enters the citric acid cycle
• Condenses with oxaloacetate to form citrate, catalyzed by citrate synthase
• This step initiates the cyclic series of reactions in the citric acid cycle
• Acetyl-CoA can also be derived from the breakdown of fatty acids (β-oxidation) and certain amino acids

Energy Production in the Citric Acid Cycle

• The citric acid cycle generates 1 ATP (or GTP) per acetyl-CoA through substrate-level phosphorylation
  • Succinyl-CoA synthetase catalyzes the formation of GTP (or ATP) when converting succinyl-CoA to succinate
• The cycle produces 3 NADH and 1 FADH2 per acetyl-CoA
  • NADH is generated during the oxidation of isocitrate, α-ketoglutarate, and malate
  • FADH2 is produced during the oxidation of succinate to fumarate
• These electron carriers (NADH and FADH2) transfer electrons to the electron transport chain for further ATP production through oxidative phosphorylation