Hydride transfer reactions, NADH reaction coordinate

If secondary isotope effects arise strictly from changes in force constants at the position of substitution, with none of the vibrations of the isotopic atom being coupled into the reaction coordinate, then a secondary isotope effect will vary from 1.00 when the transition state exactly resembles the reactant state (thus no change in force constants when reactant state is converted to transition state) to the value of the equilibrium isotope effect when the transition state exactly resembles the product state (so that conversion of reactant state to transition state produces the same change in force constants as conversion of reactant state to product state). For example in the hydride-transfer reaction shown under point 1 above, the equilibrium secondary isotope effect on conversion of NADH to NAD is 1.13. The kinetic secondary isotope effect is expected to vary from 1.00 (reactant-like transition state), through (1.13)° when the stmctural changes from reactant state to transition state are 50% advanced toward the product state, to 1.13 (product-like transition state). That this naive expectation... 

The essential features of the catalytic cycle (see Figure 10) involve the binding of NAD, the displacement of the water molecule by alcohol, the deprotonation of the coordinated alcohol to give a zinc alkoxide intermediate, the hydride transfer from the alkoxide to NAD to give a zinc-bound aldehyde, the displacement of the aldehyde by water and the release of NADH. The principal role of the zinc in the dehydrogenation reaction is, therefore, to promote deprotonation of the alcohol and thereby enhance hydride transfer... 

The more usual reactivity of NADH in functioning as a hydride donor has led to the modified proposal that hydride transfer to a Fe -NO" " complex would form HNO coordinated to the heme. The reaction of NO with this species would form N2O and regenerate the ferric heme site for further catalysis. 

Alcohol dehydrogenase is one of the active enzymes in yeast. The active site in alcohol dehydrogenase contains a zinc ion, Zn, that is coordinated to the sulfur atoms of two cysteine residues of the enzyme. The hydride reducing reagent in alcohol dehydrogenase is nicotinamide adenine dinucleotide, NADH, which transfers a hydride ion to a carbonyl compound to yield an alcohol and NAD" ", in a mechanism that is related to the Cannizzaro reaction (Sec. 16.3). 

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