Chemical Equilibrium and Metabolism Overview

Introduction to Metabolism

• Metabolism is the chemical reactions essential for life. These reactions involve the "burning" (oxidation) of nutrients in food to release energy and perform work.

Metabolism is Essential for Life

• Carbohydrates, fats, and proteins are the major nutrients involved in metabolism.
• The body uses harnessed energy for various functions like growth, maintenance, movement, reproduction, and homeostasis.
• Specific organ systems, including brain activity, muscle function, immune system, and waste processing, utilize energy.
• The processes of DNA replication, protein synthesis, maintenance of organelles and ions, and muscle contraction all require energy.

Metabolic Pathways

• Metabolic pathways are linked enzyme reactions that form networks.
• These pathways demonstrate reactants/substrates, enzymes, metabolic intermediates, and end products.
• Glycolysis is an example of a central pathway where glucose reacts in numerous steps to produce pyruvate.

Unifying Themes of Metabolic Pathways

• Many pathways across all organisms utilize similar concepts and principles.
• The pathways largely depend on the same 100 activated molecules.
• There are only a few different types of reaction mechanisms.
• Metabolic pathways are interconnected and highly regulated.
• Enzymes often exist in large complexes, facilitating substrate and product movement.

Metabolic Pathways and Energy

• Catabolic pathways are energy-releasing (exergonic) and involve the breakdown of large molecules into smaller ones, using nutrients like carbohydrates, fats, and proteins.
• Anabolic pathways are energy-requiring (endergonic) and involve the synthesis of large molecules from smaller ones using energy from catabolism.
• Amphibolic pathways are central and involve both anabolic and catabolic reactions like the tricarboxylic acid cycle.

Equilibrium and Energy

• Equilibrium is a state where there is no change. Chemical reactions proceed until forward and reverse reaction rates are equal.
• Equilibrium is considered a zero-energy state, where no more work can be done.
• Living systems maintain a state away from equilibrium by continuously using energy.

Key Concepts about Energy

• Energy is essential for life since it allows organisms to maintain themselves away from equilibrium (which would be death).
• The breakdown of nutrients releases energy.
• Cells use this energy for function and structure.

Role of Mass Action

• Reaction rates depend on concentration of reactants and products.
• Mass action ratio is the ratio of product concentration to reactant concentration
• Rates are high when the ratio is far from equilibrium.

Predicting Reaction Favourability

• Reactions that release heat/energy are exothermic/exergonic (Gibbs energy is negative, energetically favorable), while those that require heat/energy are endothermic/endergonic (Gibbs energy positive, energetically unfavorable).
• The overall free energy of a metabolic pathway can be calculated by aggregating free energy for all chemical reactions.

Energetic Coupling

• Energy from "favorable reactions" can "push" or "pull" unfavorable reactions to allow unfavorable reactions to occur. Coupled reactions are important for cell function.

Additional Forms of Cellular Energy

• Other forms of energy in cells include chemical potential (phosphorylation potential), electrochemical potential (e.g., proton gradient), and redox potential (e.g., NADH/NAD+).

Reducing Equivalents

• Reducing equivalents, like NAD(P)H, are crucial for electron transfer in metabolism.
• They are important driving forces in metabolism by shuttling electrons.

Subdivisions of Metabolism

• Catabolic pathways break down larger molecules (e.g., glucose, fats), while anabolic pathways build larger molecules.
• Catabolic reactions are generally exergonic, releasing energy, while anabolic reactions are endergonic, consuming energy.

ATP as Energy Currency

• ATP is the primary form of chemical energy in cells, with phosphorylation potential.
• ATP is produced during fuel catabolism (like glycolysis and the TCA cycle).
• ATP is used up during anabolism.

The Role of AMP

• AMP acts as a cellular signal to alert the cell that more energy is needed (low energy status).
• High AMP indicates that the cell needs more ATP production pathways to be turned on.

Metabolic Pathways and Networks

• Metabolic pathways are interconnected and require regulation.

The Steady State

• In a steady state, the concentration of chemical components and ions in a cell remains stable.
• The input and output are at equilibrium in this steady state.
• A change in internal conditions leads to a new steady state.

Regulation of Metabolic Pathways

• Both short-term and long-term mechanisms regulate metabolic pathways.
• Short-term mechanisms include enzyme behavior and the reaction properties.
• Long-term mechanisms include post-translational regulation and gene expression regulation

Pathway Convergence and Glucose Oxidation

• Major fuels converge into a primary metabolic pathway of glucose oxidation, a series of steps that are coupled to ATP synthesis.
• Glucose is a critical source of cellular energy in almost all cells.

Role of Mitochondria

• Mitochondria are critical for fuel metabolism.
• They house the TCA cycle and other processes used for oxidation (releasing energy from fuels like CHO, fats, and proteins)
• The processes of oxidative phosphorylation and the electron transport chain take place in mitochondria.

TCA Cycle as Hub

• The TCA cycle is a central metabolic pathway where many metabolic pathways converge (to fuel oxidation).
• The TCA cycle acts as an important crossroads for fuel (like glucose, fats, and proteins) oxidation.

Acetyl-CoA

• Acetyl-CoA is the main entry point for carbon into the TCA cycle.
• Many metabolic pathways result in the formation of acetyl CoA.

Oxidative Phosphorylation (Oxphos)

• Electron transfer (from molecules like NADH and FADH2) in oxidative phosphorylation generates the energy required to convert ADP to ATP.

• Oxidation of NADH and FADH2 is important to the process of oxidative phosphorylation.

• The electron transport chain transfers electrons to oxygen molecules to form water and generates the energy required for ATP synthesis.

ATP Production overview

• The energy (that glucose breakdown produces) is used to make ATP in distinct stages of the process.
• The stages consist of glycolysis, the TCA cycle, and oxidative phosphorylation.

Energy Yields from Complete Glucose Oxidation

• The oxidation of glucose through aerobic metabolism yields approximately 32-34 ATP molecules per glucose molecule.
• This is a theoretical maximum, and efficiency may differ depending on cell and state specifics

ATP Yields from Substrates

• Different substrates like glucose, fatty acids, and others yield varying amounts of ATP. The complete oxidation of glucose typically produces 32-34 ATPs. Fatty acid oxidation results in higher ATP yields.
• Aerobic (oxygen-dependent) pathways lead to higher ATP yields compared to anaerobic (oxygen-independent) ones.
• Uncoupling of oxidation processes releases some energy as heat, decreasing the ATP yield efficiency.

Role of Adenylate Kinase and AMP in Energy Homeostasis

• AMP acts as a significant indicator for the energy status of a cell, increasing when the demand for energy increases.
• Adenylate kinase interconverts ADP and AMP (converting to AMP when energy demand is high).

Uncoupling of Oxphos

• Uncouplers increase mitochondrial membrane permeability to H+ ions.
• This results in less energy for ATP synthesis and more energy released as heat.