Glycolysis and Krebs Cycle

Overview

The processes of glycolysis and the Krebs cycle (also known as the citric acid cycle or TCA cycle) are central metabolic pathways in living cells. They are responsible for the breakdown of glucose and other organic molecules to produce ATP, the universal energy currency of the cell. These pathways are fundamental to both prokaryotic and eukaryotic organisms and are essential topics in microbiology and biochemistry.

Energy in Living Systems

Introduction to Cellular Energy

• Energy Transformation: Living organisms convert energy from one form to another. For example, photosynthetic organisms convert radiant energy (light) into chemical energy, while heterotrophs obtain energy from organic molecules through cellular respiration.

• Cellular Respiration: The overall equation for aerobic respiration is:

• Electron Transfer: Electrons from food molecules are transferred through a series of redox reactions, gradually releasing energy that is captured in ATP.

Redox Reactions in Metabolism

Oxidation and Reduction

• Oxidation: Loss of electrons (often as hydrogen atoms) from a molecule, resulting in decreased potential energy.

• Reduction: Gain of electrons (often as hydrogen atoms), resulting in increased potential energy.

• Redox Reaction Example:

• Electron Carriers: Molecules such as NAD+ and FAD act as electron acceptors, becoming reduced to NADH and FADH2 respectively.

Key Electron Carriers

• NAD+ (Nicotinamide Adenine Dinucleotide):

• FAD (Flavin Adenine Dinucleotide):

• These carriers shuttle electrons from glucose oxidation to the electron transport chain, facilitating ATP production.

ATP Synthesis

Substrate-Level Phosphorylation

• ATP can be generated directly in metabolic pathways by transferring a phosphate group from a phosphorylated intermediate to ADP.

• This process occurs during glycolysis and the Krebs cycle.

• General Reaction:

Oxidative Phosphorylation

• Most ATP is produced via oxidative phosphorylation, which uses the energy from electrons transferred through the electron transport chain to drive ATP synthesis via ATP synthase.

Glycolysis

Pathway Overview

• Occurs in the cytoplasm of nearly all cells.

• Does not require oxygen (anaerobic process).

• Converts one molecule of glucose (6 carbons) into two molecules of pyruvate (3 carbons each).

• Net yield per glucose: 2 ATP (4 produced, 2 consumed) and 2 NADH.

Key Steps and Enzymes

• ATP is used in the early steps (investment phase) and produced in later steps (payoff phase).

• Important enzymes include hexokinase, phosphofructokinase, and pyruvate kinase.

• Substrate-level phosphorylation occurs at two steps, generating ATP directly.

Summary Equation

Fate of Pyruvate

• In the presence of oxygen, pyruvate enters the mitochondrion (in eukaryotes) and is oxidized to acetyl-CoA.

• In the absence of oxygen, pyruvate can be reduced via fermentation to lactate (in animals) or ethanol and CO2 (in yeast).

Pyruvate Oxidation

Conversion to Acetyl-CoA

• Occurs in the mitochondrial matrix (eukaryotes) or cytoplasm (prokaryotes).

• Each pyruvate (3C) is converted to acetyl-CoA (2C), releasing one CO2 and reducing NAD+ to NADH.

• Reaction:

Krebs Cycle (Citric Acid Cycle)

Pathway Overview

• Occurs in the mitochondrial matrix (eukaryotes) or cytoplasm (prokaryotes).

• Acetyl-CoA (2C) combines with oxaloacetate (4C) to form citrate (6C).

• Through a series of enzyme-catalyzed steps, citrate is oxidized, releasing two CO2 molecules and regenerating oxaloacetate.

• Energy captured as NADH, FADH2, and GTP (or ATP).

Summary Equation (per Acetyl-CoA)

Products per Glucose (2 Acetyl-CoA)

• 4 CO2

• 6 NADH

• 2 FADH2

• 2 GTP (or ATP)

Key Steps and Enzymes

• Major enzymes include citrate synthase, isocitrate dehydrogenase, and succinate dehydrogenase.

• Substrate-level phosphorylation occurs at the step producing GTP/ATP.

Regulation of Glycolysis and Krebs Cycle

Allosteric Regulation

• Key enzymes are regulated by feedback inhibition and activation.

• Phosphofructokinase (PFK): Inhibited by ATP and citrate; activated by AMP and ADP.

• High-energy molecules (ATP, NADH, acetyl-CoA) inhibit enzymes; low-energy molecules (ADP, AMP, NAD+, CoA) activate them.

Summary Table: Regulation of Key Enzymes

Fermentation

Regeneration of NAD+

• In the absence of oxygen, cells regenerate NAD+ by reducing pyruvate to lactate (in animals) or ethanol and CO2 (in yeast).

• This allows glycolysis to continue producing ATP anaerobically.

Summary

• Glycolysis and the Krebs cycle are central to cellular energy metabolism.

• They provide ATP, reducing power (NADH, FADH2), and metabolic intermediates for biosynthesis.

• Regulation ensures efficient energy production and prevents wasteful overproduction of ATP.

Example: During intense exercise, muscle cells switch to lactic acid fermentation to regenerate NAD+ and continue ATP production when oxygen is limited.

Additional info: The provided images and diagrams in the original file likely depict molecular structures of enzymes involved in glycolysis and the Krebs cycle, as well as electron micrographs of cellular structures. These visual aids help illustrate the molecular and cellular context of these metabolic pathways.