28 August, 2006 Chapter 4 High-Energy Bonds

Overview High-energy bonds are weak (thermodynamically unstable) covalent bonds. Input of activation energy (less than the energy of the bond to be broken) is required even for exergonic reactions. Enzymes decrease activation energy for a reaction. All biochemical pathways must be characterized by a net decrease in free energy. Coupling the breaking of high-energy bonds allows biosynthetic pathways to have a net free energy decrease. Coupling is often accomplished by the activation of precursor molecules by group transfer reactions. Pyrophosphate hydrolysis is the ultimate driving force for most biosynthetic reactions.

Activation Energy Since activation energy is on the order of kcal / mol, reactions proceed very slowly at room temperature. Enzymes orient substrates such that activation energy is within reach of the kinteic energy available under physiological conditions.

What about endergonic reactions? Endergonic reactions are coupled with strongly exergonic reactions (like the hydrolysis of ATP) such that the net  G is negative.

Example: Peptide bond formation Formation of a dipeptide from two amino acids has a  G of 1-4 kcal / mol. Free energy is added in the form of ATP hydrolysis. Why do proteins not spontaneously degrade?

Group Transfer Must have some way to harvest the energy of ATP hydrolysis, otherwise it would be lost as heat. Group transfer (A-X + B-Y -----> A-B + X-Y) serves to activate the reactant of a subsequent reaction.

Amino Acyl Group Transfer Activation Amino acids are subsequently transferred to tRNA.

Example: Polynucleotide Synthesis Formation of a dinucleotide has a  G of about 8-10 kcal / mol, because of the negative change in free energy upon hydrolysis. Free energy is again added in the form of nTP hydrolysis. Why not nDP hydrolysis?

Pyrophosphate Hydrolysis Pyrophosphate hydrolysis makes polynucleotide formation irreversible.

Van der Waals Forces Van der Waals Forces have energies in the 1 kcal / mole range, and are therefore only biologically significant in large numbers. These bonds, though, are prefect for specifying interactions based on molecular shape, like antigen-antibody interactions, where multiple Van der Waals contacts can generate binding energies of kcal / mole.

Hydrogen Bonds and Hydrophobic Interactions Hydrogen bonds usually involve hydrogen atoms covalently bound to O or N. Most have bond energies of about 3 -7 kcal / mole. These bonds are highly directional, and are useful for specifying orientation of donor and acceptor groups. In water, most molecules participate in hydrogen bonds. Molecules that can participate in this network are water-soluble. Non-polar molecules cannot form hydrogen bonds, and are not water-soluble. Hydrophobic molecules are excluded from water. This is sometimes called a hydrophobic bond.