Transferring Groups by Displacement Reactions

The majority of enzymes that are apt to be mentioned in any discussion of metabolism catalyze nucleophilic displacement reactions (Type 1, Table 10-1). These include most of the reactions by which the energy of ATP cleavage is harnessed and by which polymers are assembled from monomers. They include reactions by which pieces, large or small, are transferred onto or off of polymers as well as the reactions by which polymers are cleaved into pieces.1 3,1 

For purposes of classifying the reactions of metabolism, in this book the nucleophilic displacements are grouped into four subtypes (Table 10-1). These are displacements on (A) a saturated carbon atom, often from a methyl group or a glycosyl group (B) a carbonyl group of an ester, thioester, or amide (C) a phospho group or (D) a sulfur atom. In addition, many enzymes employ in sequence a displacement on a carbon atom followed by a second displacement on a phosphorus atom (or vice versa). 

In Chapter 9, the displacement of an iodide ion from methyl iodide by a hydroxide ion (Eq. 9-76) was considered. Can we similarly displace a methyl group from ethane, CH3-CH3, to break the C-C bond and form CH3OH The answer is no. Ethane is perfectly stable in sodium hydroxide and is not cleaved by a simple displacement process within our bodies. Likewise, long hydrocarbon chains such as those in the fatty acids cannot be broken by a corresponding process during metabolism of fatty acids. Not every structure will allow a nucleophilic displacement reaction to occur and not every anion or neutral base can act to displace another group. 

At least four factors affect the likelihood of a displacement reaction 1 3d 

Certain chemical groups, e.g., those in which an atom with unpaired electrons is directly bonded to the nucleophilic center undergoing reaction, are more reactive than others of similar basicity. This a effect has been invoked to explain the high reactivity of the poisons hydroxylamine (NH2OH) and cyanide ion4 and other puzzling results.1 

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