Graduate
  1. Physical Chemistry  1.1. Thermodynamics  1.1.1. Laws of Thermodynamics  1.1.2. Enthalpy and heat capacity  1.1.3. Entropy and free energy  1.1.4. Phase Equilibrium  1.1.5. Statistical thermodynamics  1.1.6. Thermodynamic cycle  1.1.7. Fugacity and activity  1.2. Quantum Chemistry  1.2.1. Principles of quantum mechanics  1.2.2. Schrödinger Equation  1.2.3. Particle in a box  1.2.4. Operators and eigenvalues  1.2.5. Atomic orbitals  1.2.6. Molecular orbital theory  1.2.7. Perturbation theory  1.2.8. Valence bond theory  1.2.9. Hybridization and chemical bonding  1.3. Chemical kinetics  1.3.1. Rate laws and reaction mechanisms  1.3.2. Collision theory  1.3.3. Transition state theory  1.3.4. Enzyme Kinetics  1.3.5. Chain Reactions and Polymerization  1.3.6. Photochemical reactions  1.4. Statistical mechanics  1.4.1. Partitioning functions  1.4.2. Molecular distribution functions  1.4.3. Boltzmann Distribution  1.4.4. Bose–Einstein and Fermi–Dirac statistics  1.5. Spectroscopy  1.5.1. Rotational Spectroscopy  1.5.2. Vibrational Spectroscopy  1.5.3. Electronic Spectroscopy  1.5.4. Nuclear magnetic resonance spectroscopy  1.5.5. Mass Spectrometry  1.5.6. Raman Spectroscopy  1.5.7. Electron paramagnetic resonance spectroscopy  1.6. Surface and colloidal chemistry  1.6.1. Absorption isotherm  1.6.2. Surface tension and wetting  1.6.3. Colloidal Stability  1.6.4. Catalysis  1.6.5. Emulsions and micelles  1.7. Electrochemistry  1.7.1. Nernst equation  1.7.2. Electrochemical cells  1.7.3. Conductivity and mobility  1.7.4. War  1.7.5. Fuel cells  1.7.6. Electrolysis
  2. Organic chemistry  2.1. Reaction mechanism  2.1.1. Nucleophilic substitution reactions  2.1.2. Electrophilic addition reactions  2.1.3. Elimination reactions  2.1.4. Rearrangement reactions  2.1.5. Radical reactions  2.1.6. Pericyclic reactions  2.2. Spectroscopy and structural determination  2.2.1. UV-Vis Spectroscopy  2.2.2. IR Spectroscopy  2.2.3. NMR Spectroscopy  2.2.4. Mass Spectrometry  2.2.5. X-ray crystallography  2.3. Stereoscopic  2.3.1. Chirality and optical activity  2.3.2. Structural analysis  2.3.3. Geometrical isomerism  2.3.4. Dynamic Stereochemistry  2.4. Organometallic Chemistry  2.4.1. Organolithium and organomagnesium reagents  2.4.2. Palladium-catalyzed cross-coupling reactions  2.4.3. Transition Metal Complexes  2.4.4. Metal–carbon bond  2.5. Polymer chemistry  2.5.1. Polymerization mechanism  2.5.2. Polymer Characteristics  2.5.3. Biodegradable Polymer  2.5.4. Conducting polymer  2.5.5. Supramolecular polymers  2.6. Medicinal chemistry  2.6.1. Drug design and development  2.6.2. Pharmacokinetics and pharmacodynamics  2.6.3. Structure-activity relationships  2.6.4. Molecular docking and drug screening
  3. Inorganic chemistry  3.1. Coordination chemistry  3.1.1. Crystal field theory  3.1.2. Ligand field theory  3.1.3. Spectrochemical Series  3.1.4. Chelation and stability  3.2. Organometallic Chemistry  3.2.1. Metal Carbonyls  3.2.2. Catalysis by organometallic complexes  3.2.3. Metallocenes  3.3. Bio-inorganic chemistry  3.3.1. Metalloproteins and enzymes  3.3.2. The role of metals in biological systems  3.3.3. Metal ion transport and storage  3.4. Solid state chemistry  3.4.1. Crystal Structures  3.4.2. Band theory of solids  3.4.3. Superconductors  3.4.4. Defects in the crystal  3.5. Lanthanides and Actinides  3.5.1. Electronic configuration in lanthanides and actinides  3.5.2. Coordination chemistry of the lanthanides  3.5.3. Magnetic Properties of Lanthanides
  4. Analytical chemistry  4.1. Chromatography  4.1.1. Gas Chromatography  4.1.2. High Performance Liquid Chromatography  4.1.3. Thin Layer Chromatography  4.2. Spectroscopic Techniques  4.2.1. Atomic absorption spectroscopy  4.2.2. X-ray diffraction  4.2.3. Inductively coupled plasma spectroscopy  4.3. Electroanalytical methods  4.3.1. Potentiometry  4.3.2. Voltammetry  4.3.3. Colometry  4.4. Mass Spectrometry  4.4.1. Ionization Technique  4.4.2. Fragmentation Pattern  4.5. Chemometrics  4.5.1. Multidisciplinary analysis  4.5.2. Machine Learning in Chemistry
  5. Theoretical and Computational Chemistry  5.1. Molecular dynamics simulation  5.1.1. Force fields and energy minimization  5.1.2. Monte Carlo simulation in molecular dynamics simulations  5.2. Quantum chemical methods  5.2.1. Hartree–Fock theory  5.2.2. Density functional theory  5.2.3. Semi-empirical methods  5.3. Computational drug design  5.3.1. Molecular Docking  5.3.2. QSAR Modeling  5.3.3. Virtual Screening
  6. Biochemistry  6.1. Enzyme Kinetics  6.1.1. Michaelis-Menten kinetics  6.1.2. Inhibition mechanism  6.2. Metabolism and Bioenergetics  6.2.1. Glycolysis  6.2.2. Citric acid cycle  6.2.3. Electron transport chain  6.3. molecular Biology  6.3.1. DNA replication and repair  6.3.2. Protein synthesis  6.3.3. Gene Regulation  6.4. Structural Biochemistry  6.4.1. Protein Folding  6.4.2. Membrane Biophysics
  7. Environmental Chemistry  7.1. Atmospheric Chemistry  7.1.1. Greenhouse gases  7.1.2. Ozone depletion  7.1.3. Air pollutants and smoke  7.2. Water Chemistry  7.2.1. pH and water hardness  7.2.2. Wastewater treatment  7.2.3. Aquatic Chemistry  7.3. Soil Chemistry  7.3.1. Heavy metal contamination  7.3.2. Soil pH and Buffering  7.3.3. Nutrient cycling  7.4. Toxicology and Chemical Safety  7.4.1. Toxicokinetics  7.4.2. Risk Assessment in Toxicology and Chemical Safety in Environmental Chemistry  7.4.3. Effects of pollutants on the environment

Graduate → Biochemistry → Metabolism and Bioenergetics ↓


Glycolysis


Introduction

Glycolysis is a basic metabolic pathway involved in breaking down glucose, a simple sugar, into pyruvate. This process is essential in cellular respiration, providing energy in the form of ATP and intermediates for other metabolic pathways. Glycolysis occurs in the cytoplasm of cells and is the first step in the catabolism of carbohydrates. Unlike other metabolic processes, glycolysis is anaerobic, meaning it does not require oxygen.

Glycolytic pathway

Glycolysis involves a series of ten enzyme-catalyzed reactions. These reactions can be divided into two main phases: the energy investment phase and the energy payoff phase.

Energy investment phase

  • Step 1 - Phosphorylation of Glucose: 
    glucose + ATP → glucose-6-phosphate + ADP
    The hexokinase enzyme catalyzes the phosphorylation of glucose using a molecule of ATP, producing glucose-6-phosphate.
  • Step 2 - Isomerization: 
    glucose-6-phosphate → fructose-6-phosphate
    The phosphoglucose isomerase enzyme converts glucose-6-phosphate to fructose-6-phosphate.
  • Step 3 - Second phosphorylation: 
    fructose-6-phosphate + ATP → fructose-1,6-bisphosphate + ADP
    Phosphofructokinase-1 phosphorylates fructose-6-phosphate using another ATP molecule, resulting in the formation of fructose-1,6-bisphosphate.
  • Step 4 - Cleavage: 
    fructose-1,6-bisphosphate → dihydroxyacetone phosphate + glyceraldehyde-3-phosphate
    Aldolase splits fructose-1,6-bisphosphate into two three-carbon sugars: dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.
  • Step 5 - Isomerization of dihydroxyacetone phosphate: 
    dihydroxyacetone phosphate ↔ glyceraldehyde-3-phosphate
    Triose phosphate isomerase catalyzes the reversible conversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate. At this point, two molecules of glyceraldehyde-3-phosphate are formed for each glucose molecule entering glycolysis.

Energy payback phase

  • Step 6 - Oxidation and Addition of Phosphate: 
    2 glyceraldehyde-3-phosphate + 2 NAD+ + 2 Pi → 2 1,3-bisphosphoglycerate + 2 NADH + 2 H+
    Glyceraldehyde-3-phosphate dehydrogenase catalyzes the oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, generating NADH in the process.
  • Step 7 - Transfer of phosphate to ADP: 
    2 1,3-bisphosphoglycerate + 2 ADP → 2 3-phosphoglycerate + 2 ATP
    Phosphoglycerate kinase catalyzes the transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP, producing ATP and 3-phosphoglycerate.
  • Step 8 - Conversion: 
    2 3-phosphoglycerate → 2 2-phosphoglycerate
    Phosphoglycerate mutase shifts the position of the phosphate group on 3-phosphoglycerate to form 2-phosphoglycerate.
  • Step 9 - Dehydration: 
    2 2-phosphoglycerate → 2 phosphoenolpyruvate + 2 H2O
    Enolase removes a water molecule from 2-phosphoglycerate, forming phosphoenolpyruvate (PEP).
  • Step 10 - Formation of pyruvate and ATP: 
    2 phosphoenolpyruvate + 2 ADP → 2 pyruvate + 2 ATP
    Pyruvate kinase transfers a phosphate group from PEP to ADP, yielding the end product pyruvate and additional ATP.

Overall equation

The overall chemical equation for glycolysis, considering a single molecule of glucose, is as follows:

C6H12O6 + 2 NAD+ + 2 ADP + 2 Pi → 2 pyruvate + 2 NADH + 2 H+ + 2 ATP + 2 H2O

Energy yield

Glycolysis results in a net gain of two ATP molecules per molecule of glucose. Four ATP molecules are produced during the energy payoff phase, but two are consumed during the energy investment phase. Additionally, two NADH molecules are produced, which can be used in the electron transport chain to produce more ATP under aerobic conditions.

Regulation of glycolysis

Glycolysis is tightly regulated to meet the energy demands of the cell. Key regulatory enzymes include hexokinase, phosphofructokinase-1 (PFK-1), and pyruvate kinase.

  • Hexokinase: when its concentration is high, it is inhibited by its product, glucose-6-phosphate.
  • PFK-1: The most important regulatory point in glycolysis, activated by AMP and fructose-2,6-bisphosphate, and inhibited by ATP and citrate.
  • Pyruvate kinase: activated by fructose-1,6-bisphosphate and inhibited by ATP and alanine.

Importance of Glycolysis

Glycolysis is an essential metabolic pathway for several reasons:

  • It is the primary source of ATP in anaerobic conditions, such as during intense exercise.
  • Intermediates produced in glycolysis, such as glyceraldehyde-3-phosphate, provide the building blocks for biosynthetic pathways.
  • Pyruvate, the end product of glycolysis, can be used in a variety of metabolic pathways, including the citric acid cycle and fermentation.

Examples and visualizations

Let us explore visualization of the glycolytic pathway using simplified reactions to enhance understanding.

Glucose to pyruvate pathway:

The following is a simplified flow diagram of how glucose is converted to pyruvate in glycolysis:

sugar Glucose 6 Phosphate , Phosphoenolpyruvate Pyruvate

In this diagram, the arrows show the flow of carbon atoms along the glycolytic pathway from glucose to pyruvate, with important intermediates such as glucose-6-phosphate and phosphoenolpyruvate visible along the pathway.

Energy changes during glycolysis:

The following simplified chart shows the steps of energy investment (ATP used) and energy gain (ATP generated) during glycolysis:

Use of ATP ATP produced ATP produced energy flow

Conclusion

Glycolysis is a vital biochemical pathway that plays a central role in cellular metabolism and energy production. As the primary route of carbohydrate catabolism, it serves to convert glucose to pyruvate while harvesting energy and generating precursors for other metabolic reactions. While seemingly simple, the regulation and integration of glycolysis with other metabolic pathways exemplify the complexity and efficiency of cellular biochemistry. Understanding glycolysis provides a foundation for understanding how cells metabolize energy and respond to changes in energy demand.


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Glycolysis

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