BCH210 second half

Catabolism and Anabolism are Interrelated

Catabolism: breaking things down

Anabolism: buildiing things up

Bioenergetics and Metabolism

• Metabolism involves catabolism of compounds, releasing free energy

  • can be stored in ATP or other high energy intermediates

• Anabolic processes syntehsize larger macromolecules using simple building blocks and energy

• Gibbs free energy changes (and enzyme) influence the metabolic flux or conversion of metabolites through the pathways

Review of a Chemical Reaction Diagram

Exergonic: substrate energy level higher than product

Endergonic: subtrate energy level lower than product

Activation energy: energy barrier needed to overcome

Gibbs Free Energy and Reactions

Standard Free Energy Change

Keq’ > 1 — Gnaught is negative: exergonic, spontaneous

Keq’ < 1 — Gnaught is positive: endergonic, non-spontaneous

Keq’ = 1 — Gnaught is 0: reaction is reversible

Actual Free Energy Change

Negative ΔG – exergonic, spontaneous

Positive ΔG – endergonic, non-spontaneous

Reactions can be reversible if ΔG = 0

• concentration of substrates and products determine diretionality to overcome an unfavourable standard ΔG°′

Thermodynamics and Biochemical Reactions

The Gibbs free energy under standard conditions (ΔG°′ - 1M, 298K, pH 7.0) depends on the nature of the reactants and their concentrations at equilibrium (K’eq)

The cellular Gibbs free energy (ΔG) is dependent on the cellular concentrations of substrate and product and ΔG°′

An enzyme can couple a favourable and unfavourable reaction to produce an overall favourable reaction

Coupled Reactions (or Pathways)

ATP, ADP, AMP

Resonance Stabilization

Resonance Stabilization in Inorganic phosphate

Inorganic phosphate more stable than when attached to ATP

ATP Phosphoryl Transfer Potential

The change in free energy can be used to activate molecules for reactions that are highly unfavourable or found in anabolic pathways

Major issue - how ATP and ADP are remade from ADP or AMP for future use...

Review - ATP

• Nucleotide made of adenine, ribose and three phosphates

  • α, β and γ phosphates: linked by phosphoanhydride bonds and an ester bond to sugar

• Involved in both catabolic pathways and anabolic pathways via phosphate group transfer reactions

• Free energy change is dependent on the structures and stability of the substrates vs product

• Free energy changes not fixed, polar phosphates are ionizable and pH dependent

• Metal ions help stabilize ATP

Compounds with similar phosphoryl transfer potentials

no energy change

Phosphoryl Transfer Potential in Muscle — phosphocreatine

Phosphocreatine stores phosphate — can be coupled with phosphate transfer onto ADP to make it energetically favourable

• during exercise hydrolyze phosphocreatine

• during rest resupplement phosphocreatine

Creatine Kinase Reversibility

Normally more ATP and creatine made

If ATP levels rise, can shift to make more ADP and phosphocreatine