Metabolism Overview

Introduction to Life and Electrons

Importance of the First Law

Metabolic Processes

Overview of Metabolism

• Oxidation of reduced fuels occurs stepwise and is controlled.

• Key Redox Cofactors: NAD+ and NADP+ (pyridine nucleotides) can dissociate; FAD and FADH2 (flavins) are usually bound to enzyme active sites.

Goals of Metabolism

1. Extract energy (ATP).

2. Extract reducing power (NADPH) for biosynthesis.

3. Obtain precursors for macromolecules.

4. Synthesize necessary macromolecules using available precursors and energy.

Metabolic Pathways

Pathway Types

• Catabolic Pathways: Break down large molecules into smaller ones, converting fuel energy into usable biological energy.

• Anabolic Pathways: Utilize intermediates and energy from catabolism to synthesize various biomolecules (e.g., glucose, DNA).

• Amphibolic Pathways: Serve dual functions, aiding both catabolism for energy and anabolism for building blocks (e.g., citric acid cycle).

Connectivity of Metabolism

• Integration: All metabolic processes (catabolism, anabolism) are interconnected and work together to maintain energy balance and produce necessary products.

Regulation of Metabolic Pathways

• Regulation occurs through controlling enzyme amounts, catalytic activities, substrate availability, and cell energy state (ATP/ADP ratio).

• Low ATP/ADP signals favor catabolism; high ATP levels inhibit catabolism to conserve nutrients.

Energy Charge and Metabolic Flux

• Energy charge defines the balance and regulation of metabolic pathways:

  • High ADP concentration stimulates catabolic enzyme activities, indicating low energy and thus increasing ATP production.

  • High ATP concentration inhibits catabolism and promotes nutrient storage.

Extraction of Energy from Fuels

Stages of Energy Extraction

1. Breakdown large biomolecules into smaller components.

2. Production of acetyl-CoA or citric acid cycle intermediates (some ATP produced).

3. Complete oxidation of acetyl-CoA in the citric acid cycle and oxidative phosphorylation (95% ATP produced).

Reaction Types

Endergonic vs. Exergonic Reactions

• Endergonic Reactions: Require input energy to proceed.

• Exergonic Reactions (Catabolism): Release energy stored in nutrients, reflected in ATP's phosphoanhydride bonds.

• ATP cycle couples exergonic reactions with endergonic reactions, facilitating the transfer of free energy.

Energy Coupling

• Process: ATP hydrolysis and phosphoryl group transfer couple non-spontaneous (endergonic) reactions with spontaneous (exergonic) reactions.

• ATP is initially used to store energy from a catabolic reaction before being utilized for an anabolic reaction.

Mechanisms of ATP Formation

Mechanisms

1. Substrate-level phosphorylation: Direct transfer of a high-energy phosphate to ADP from a substrate.

2. Oxidative phosphorylation: Utilizes proton gradient and chemiosmosis to produce ATP.

Major Sources of ATP

1. Oxidative phosphorylation: Largest ATP producer.

2. Citric acid cycle (Krebs cycle).

3. Glycolysis: Sole source of ATP in red blood cells.