1. Chap 8. Stereochemistry of Enzymatic Reactions
Enzyme catalysis: stereospecific
A knowledge of the basic principle of stereochemistry: essential for understanding enzyme mechanisms
Comparison of the stereochemistry of the substrates and products: a clue of intermediates

2. A. Optical Activity and Chirality
Chiral: lack of a plane or center of symmetry
Prochiral: potentially chiral, CR2R’R”

3. 1. Notation RS convention The higher priority:
The higher atomic number
The higher mass number
The atomic number of the next atoms out
-SH > -OR > -OH > -NHCOR > -NH2 > -CO2R > -CO2H
> -CHO > -CH2OH > -C6H5 > -CH3 > -T > -D > -H
Re- and Si-faces for a compound containing a trigonal carbon atom

4. 2. Differences between the Stereochemistries of Enzymatic and Nonenzymatic Reactions
Enzymatic reactions: on the surface of an asymmetric protein
Nonenzymatic reactions: in a homogeneous solution
J. Am. Chem. Soc., 2005, 127,

5. 3. Conformation and Configuration
Conformation: any one of a molecule’s instantaneous orientations in space caused by free rotation about its single bonds
Configuration: the geometry about a rigid or dissymmetric part of a molecule

6. B. Examples of Stereospecific Enzymatic Reactions
NAD+- and NADP+-dependent oxidation and reduction
Stereochemistry of the fumarase-catalyzed hydration of fumarate
Demonstration that the enediol intermediate in aldose-ketose isomerase reactions is syn
Use of locked substrates to determine the anomeric specificity of phosphofructokinase

7. C. Detection of Intermediates from Retention or Inversion of Configuration at Chiral Centers
Stereochemistry of nucleophilic reactions:
SN2: inversion
SN1: a racemic product
Two successive inversion: retention
The validity of stereochemical arguments:
Stereochemical evidence can only rule out alternative pathways
Intermediates in reactions of lysozyme and b-galactosidase:
both retention of configuration at the C-1 carbon
lysozyme: a carbonium ion fromed in an SN1 reaction
b-galactosidase: two successive SN2 displacements

8. D. The Chiral Methyl Group E. Chiral Phosphate

9. F. Stereoelectronic control of enzymatic reactions
There is a relationship between the energitics of the electronic changes that occur in bond making and breaking and the conformation or configuration of the reactants
An optimal conformation for a particular reaction could be important in enzymatic reactions for controlling product formation and minimizing side reactions

10. 1. Pyridoxal phosphate reactivity
A Schiff base intermediate formed: 8.44
Three possible bond cleavage to give different products: 8.45
2. Stereoelectronic effects in reactions of proteases
A tetrahedral intermediate formed: 8.47
The lowest-energy transition state for breakdown is anti to the leaving group: 8.48
Perhaps inversion on N is an essential step