Metabolism: Catabolism and Anabolism

• Metabolism encompasses catabolic and anabolic processes, involving energy extraction and synthesis of new materials through interconnected chemical reactions.

Energy and Metabolism

• Metabolism requires energy for mechanical work, active transport, and biosynthesis.
• Phototrophs obtain energy from sunlight, while chemotrophs capture energy via chemical oxidation.

Metabolic Pathways

• Metabolic pathways degrade fuels and construct large molecules through a series of linked reactions, such as glycolysis converting glucose to pyruvate.

Oxidation

• Glucose metabolism involves glycolysis, the TCA cycle, and the electron transport chain, ultimately oxidizing carbon to CO2 and producing water.

Common Themes

• ATP acts as an energy currency, linking exergonic and endergonic pathways.
• Metabolic reactions utilize simple mechanisms and are highly regulated, with enzymes often organized into large complexes for increased efficiency.

Catabolism and Anabolism

• Catabolism breaks down complex molecules, capturing energy, while anabolism constructs complex molecules, requiring energy. Amphibolic pathways can be either catabolic or anabolic based on cellular energy conditions.

Thermodynamics

• A metabolic pathway requires specific reactions that are thermodynamically favored, with an overall negative change in free energy (ΔG).

Free-Energy Change

• The overall free-energy change in a coupled series of reactions equals the sum of individual free-energy changes, allowing unfavorable reactions to be coupled with favorable ones.

ATP as Energy Currency

• ATP is the universal free-energy donor in biological systems, transformed from energy derived from food oxidation and light. It consists of adenine, ribose, and a triphosphate unit, active in complex with Mg2+ or Mn2+.

ATP Hydrolysis

• ATP hydrolysis is exergonic due to phosphoanhydride linkages, releasing free energy through new covalent bonds, noncovalent interactions with water, and increased entropy. ΔG for ATP hydrolysis under cellular conditions is approximately -50 kJ mol-1.

Nucleotides

• Enzymes catalyze phosphoryl group exchange among nucleotides. Nucleoside monophosphate kinases phosphorylate nucleoside monophosphates, while nucleoside diphosphate kinases phosphorylate nucleoside diphosphates.

ATP Hydrolysis and Equilibrium

• ATP hydrolysis drives metabolism by shifting the equilibrium of coupled reactions, making unfavorable conversions possible.

Phosphoryl-Transfer Potential

• Phosphoryl-transfer potential compares the tendency of molecules to transfer a phosphoryl group, with ATP having a higher potential than glycerol 3-phosphate due to greater resonance stabilization, electrostatic repulsion, increased entropy, and hydration.

High-Energy Compounds

• Compounds with high phosphoryl-transfer potential, such as phosphoenolpyruvate and 1,3-bisphosphoglycerate, can be used to make ATP from ADP.

Creatine Phosphate

• Creatine phosphate serves as a reservoir of high-potential phosphoryl groups in muscle, with creatine kinase catalyzing ATP regeneration.

Carbon Fuels

• ATP must be constantly regenerated from ADP. Carbon atoms in fuels are oxidized to yield CO2, with more reduced carbons releasing more energy upon oxidation.

Fats vs Carbohydrates

• Fats are a more efficient fuel source than carbohydrates because they contain more reduced carbons.

Glyceraldehyde 3-Phosphate

• Oxidation of glyceraldehyde 3-phosphate generates 1,3-bisphosphoglycerate (1,3-BPG) and captures electrons via NAD+ to form NADH.

Ion Gradients

• Oxidation of fuel molecules or phototrophy produces electrochemical potentials of ion gradients across membranes, which can power ATP synthesis. Oxidative phosphorylation generates 90% of ATP in animals.

Phosphate Esters

• Phosphate esters are thermodynamically unstable, kinetically stable in water, essential for energy manipulation by enzymes, and alter molecule conformation and behavior.

Energy Extraction

• Food energy extraction occurs in three phases: breakdown of large molecules, degradation to simple units, and ATP production from acetyl CoA.

Activated Carriers

• Activated carriers are small molecules with added chemical groups or electrons, acting as coenzymes or cosubstrates (e.g., ATP).

NAD(P)H

• NAD+ accepts a proton and two electrons to form NADH, while FAD accepts two protons and two electrons to form FADH2 in fuel oxidation.

NADPH

• NADPH is the electron donor in reductive biosynthesis, needed for reducing precursors in biosynthesis.

Coenzyme A (CoA)

• Coenzyme A (CoA) carries acyl groups, forming thioester bonds, with acetyl linked to CoA called acetyl CoA. Acyl group transfer is exergonic due to thioester instability.

Metabolism Aspects

• Kinetic stability allows enzymatic control, and a small set of carriers accomplishes most activated group exchanges in metabolism.

Types of Metabolic Reactions

• Metabolic reactions include oxidation-reduction, group transfer, hydrolytic cleavage, carbon bond cleavage, isomerization, and ligation requiring ATP cleavage.

Metabolic Processes and Regulation

• Metabolic pathways must be regulated to create a stable biochemical environment (homeostasis), achieved by altering enzyme amounts, restricting substrate accessibility, and regulating catalytic activity.