Electron delocalization, enzymic

The principles of ESR spectroscopy are very similar to NMR spectroscopy but the technique gives information about electron delocalizations rather than molecular structure and it enables the study of electron transfer reactions and the formation of paramagnetic intermediates in such reactions. In some situations, information regarding molecular structure can be obtained when suitable prosthetic groups are part of a molecule, e.g. FMN (flavin mononucleotide) in certain enzymes or the haem group in haemoglobin. Sometimes it is possible to attach suitable groups to molecules to enable their reactions to be monitored by ESR techniques. Such spin labels as they are called, are usually nitroxide radicals of the type... 

The catalytic strategy is familiar from our discussion of PLP-dependent reactions reaction via a Schiff base, probable medium control of the decarboxylation, and desolvation of the carboxyl group on binding to the enzyme. What is most surprising is that pyruvate, with its very small electron sink, works as efficiently as PLP, which allows for more extensive electron delocalization. The specialness of PLP in enzymic catalysis must lie in other factors. 

By comparison, decarboxylation is largely a kinetic problem. Enzymes have developed a variety of strategies for stabilizing the anionic intermediate that is produced in the decarboxylation step. Metal ion stabilization of enolates is a common theme, particularly for decarboxylation of /8-keto acids. The most elegant solutions are perhaps the extensive electron delocalizations seen in pyri-doxal phosphate and thiamin pyrophosphate. 

In the human body, an enzyme called HGPRT catalyzes the nucleophilic substitution reaction shown here. The pyrophosphate group is an excellent leaving group because the electrons released when the group departs, like, the electrons released when a sulfonate group departs, are stabilized by electron delocalization. 

Pullman and Pullman (1963), in their seminal book on quantum biochemistry, noted the central role occupied in life processes by molecules possessing partly or completely conjugated systems. These molecules include the coenzymes, whose precursors are the water-soluble vitamins. Stabilization of transition states by electronic delocalization, transmission of electronic perturbations over several atoms, and facilitation of electron mobility were suggested as explaining, at least in part, the reaction capabilities of coenzymes. An additional role for coenzymes (Jencks, 1975) is the provision for optimal binding interactions with specific subsites on the enzyme, the so-called "anchor principle" discussed above. In this section, we shall consider the mechanism of action of the major coenzymes. A general description of coenzyme reaction mechanisms is available (Lowe and Ingraham, 1974). 

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