Basics of Biochemistry Enzyme Reaction Thermodynamics Ashish Kr Dwivedi, PhD
Transition state ( 4G AG Ground state Ground state Reaction coordinate
Transition state ) AG uncat -- ]hGcat ES-EP- - Reaction coordinate
AG' (kJ/mol) eq 10 6 10-5 10-4 10-3 10-2 10-1 34.2 28.5 22.8 17.1 11.4 5.7 0.0 5.7 11.4 17.1 1 101 102 103
Source of the energy for the lowering of the activation energies Rearrangements of covalent bonds during an enzyme-catalyzed reaction. Chemical reactions of many types take place between substrates and enzymes' functional groups (specific amino acid side chains, metal ions, and coenzymes) Catalytic functional groups on an enzyme may form a transient covalent bond with a substrate and activate it for reaction, or a group may be transiently transferred from the substrate to the enzyme. In many cases, these reactions occur only in the enzyme active site Covalent interactions between enzymes and substrates lower the activation energy (and thereby accelerate the reaction) by providing an alternative, lower-energy reaction path. The specific types of rearrangements that occur
Much of the energy required to lower activation energies is derived from weak, noncovalent interactions between substrate and enzyme. The interaction between substrate and enzyme in this complex is mediated by the same forces that stabilize protein structure, including hydrogen bonds and hydrophobic and ionic interactions
Formation of each weak interaction in the ES complex is accompanied by release of a small amount of free energy that provided a degree of stability to the interaction. The energy derived from enzyme-substrate interaction is called binding energy, Ge. Its significance extends beyond a simple stabilization of the enzyme-substrate interaction. Binding energy is a major source of free energy used by enzymes to lower the activation energies of reactions.
Two fundamental and interrelated principles provide a general explanation for how enzymes use noncovalent binding energy: 1. Much of the catalytic power of enzymes is ultimately derived from the free energy released in forming many weak bonds and interactions between an enzyme and its substrate. This binding energy contributes to specificity as well as to catalysis. 2. Weak interactions are optimized in the reaction transition state; enzyme active sites are complementary not to the substrates per se but to the transition states through which substrates pass as they are converted to products during an enzymatic reaction.
, AGB! uncat | AG uncat AG cat AG ES
Ashish Kr Dwivedi
Former Scientist (IIT Kanpur), Authored 10+ Peer Reviewed International Publications, PhD (IITK) Chief Mentor Triyambak Life Sciences