Metabolism

What is metabolism?
What do we mean by the term metabolism?

• Metabolism is the sum of all the chemical reactions of a cell.
• The totality of the chemical reactions.

• Catabolism: breakdown, generally through oxidation reactions, of complex molecules to simple ones.

• Anabolism: synthesis, generally through reduction reactions, of complex molecules from simple ones.

• Diversity of chemical reactions -- literally hundreds of highly specific reactions.
• Reactions proceed at high rates despite low temperature and pressure.
• Reactions have high specificity-- completely stereoselective. Stereoselective = preferential formation of one stereoisomer.

• The individual reactions usually are chemically simple.

• Enzymes catalyze simple, small, discrete chemical reactions.

• Organized

• The different chemical reactions, each catalyzed by an enzyme, are organized into metabolic pathways.

• Organized chemistry
• The progressive summation of enzyme catalyzed reactions.
• The product of the first enzyme is the substrate for the second, etc...........
• The sum of the small discrete chemical reactions results in a major chemical transformation that is a metabolic pathway.

• The enzymes in a metabolic sequence sometimes are organized into *metabolons*, which is a loose association of enzymes, weakly held together by just a few non-covalent bonds, forming a large multienzyme complex.
• The advantage of metabolons is that substrates are channeled from one enzyme to another in the sequence, so that rates of reaction are not limited by simple 3-dimensional diffusion.

• allow for the controlled release release of small amounts of energy at each enzyme catalyzed step
  rather than the single release of a large amount of energy associated with the pathway as a whole.
• allow for branches and interconnections to other metabolic pathways -- versatility and flexibility.

• No: metabolism is organized. Individual enzymes may be loosely associated with each other into what is termed a metabolon, or may be strongly associated with each other in a large complex, or may be compartmentalized in organelles (mitochondria, chloroplasts, nucleus).

• Specific control mechanisms that regulate one or more enzymes in the pathway.

• catabolic = convergent
• anabolic = divergent

• catabolism:
  • the oxidation of complex molecules into their monomeric units and then to simpler compounds and finally to CO2, H2O, ammonia, sulfate and phosphate (CHOPNS)
  • does not require large numbers of complex pathways because catabolic routes converge on the central pathways of metabolism
  • central pathways capture the chemical bond energy and conserve it as ATP

• anabolism:
  • the central pathways are the starting point for the reductive biosynthesis of new complex molecules from simple ones
  • does not require large numbers of complex pathways because divergent pathways are branched (arboreal) and often use common intermediates
  • uses the chemical energy of ATP
  • ATP work may be mechanical, vectorial (transport) or chemical.

What are the first and second laws of thermodynamics?

1. Energy is conserved
2. Entropy is increasing

• spontaneous processes increase disorder
• organized energy is spontaneously converted into disorganized energy (heat).

What do cells obtain energy from?
What do they do with it?

• Cells transform energy from one type to another.
  • chemical energy --> work and heat
  • light energy --> work and heat

• Cells are open systems
• they exchange energy with their surroundings
• open systems maintain a disequilibrium
• there is a continual input of matter and energy from the surroundings
• which is transformed and conserved by the cell in its metabolism
• with a continual output of matter and energy back to the surroundings.

• Chemical systems are spontaneously moving towards equilibrium
• Cells are open systems displaced from equilibrium but spontaneously moving towards it.
• The chemical energy resulting from this displacement of spontaneous reactions is available to do work
• G = H - TS, the difference between the energy of the system, H, and a measure of its disorder amplified by T, random motion, is the energy available to do useful work, G, or free energy.
• For a metabolic pathway, dG = dH - TdS, the difference in free energy between substrates and products may be conserved in the formation of chemical energy such as ATP.
• At equilibrium there is no net transformation and no useful work, dG = 0
• Therefore the open systems of cells are in a steady state, displaced from equilibrium by a continual input of substrates and removal of products.
• Because they are displaced from equilibrium, useful chemical or mechanical work can be derived from metabolism.

• Rearrangement of chemical bonds
• Derive energy from breaking chemical bonds

• Specific control mechanisms that regulate one or more enzymes in the pathway.
• Allosteric regulation -- an end product feeds back to control an enzyme early in the pathway

Principles:

• Continual turnover
  • Exchange of matter and energy with the environment

• Multiplicity of utilization
  • Metabolites are used in many different ways.

• Gradual change
  • Chemically simple reactions
  • Sum is a metabolic pathway

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Bich 107 lecture notes on Metabolism were last updated 10/07/03

Comments to Martyn Gunn