Push-pull general acid-base catalysis

The impact of nucleophilic and electrophilic groups of the active center on the substrate at the contact area in the enzyme-substrate complex (the effect of synchronous intramolecular catalysis). The polyfunctional catalysis involves a great many processes push-pull mechanisms, processes involving a relay charge transfer, as well as a general acid-base catalysis. Presumably, the enzyme in the initial state of the enzymatic reaction already contains structural elements of the transition state and in this case the reaction must be thermodynamically more advantageous. 

Atom Variations E2 Heteroatom Variants, Dehalogenation, Fragmentation Vinylogous Variations Sn2 and E2. 1,4 additions Extent of Proton Transfer Variations General Acid and General Base Catalysis of Additions and Eliminations, Summary by Media, Push-Pull Catalysis of Enolization... 

We ean also expect that enzyme active sites with appropriately positioned acidic and basic groups can easily do general acid, general base, and push-pull catalysis. 

The addition or removal of a proton can promote electron flow, i.e., bond formation and breakage, during the reaction. As far as enzymes are concerned, only general acid or base catalysis can occur, because enzymes have no means of concentrating or OH ions. A number of amino acid side chains can act as proton donors or acceptors, and in many Zn-dependent enzymes, such as carboxypeptidase. the metal ion acts as an effective Lewis acid to enhance polarization of the carbonyl moiety of the amide bond. Among the amino acids His (which has a pKa generally close to 7) plays an especially important role in enzyme catalysis, because at neutral pH, there is a good balance between its protonated and deprotonated forais. In most cases, enzymes have suitably positioned pairs of side chains to provide push and pull of electrons. 

Acyl Transfer Blfunctlcfnal Catalysis- Many mechanisms for enzjrme cataly-sls postulate cooperative ("push-pull") catalysis by an acid-base pair in the active site. The analogous bifunctional intramolecular catalysis has been widely sought the evidence presented generally consists of a maximum rate at a pH sufficiently acidic for the acid-catalytic function to be pro-tonated yet sufficiently basic for the base-catalytic function to be free. The hydrolysis of hexachlorophene monosuccinate (14). for example, exhibits such a rate maximum at pH 6.8 (between pK 5.20 for Che carboxyl group and... 

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