Mirror-image enzyme

The enzyme-catalyzed interconversion of acetaldehyde and ethanol serves to illustrate a second important feature of prochiral relationships, that ofprochiral faces. Addition of a fourth ligand, different from the three already present, to the carbonyl carbon of acetaldehyde will produce a chiral molecule. The original molecule presents to the approaching reagent two faces which bear a mirror-image relationship to one another and are therefore enantiotopic. The two faces may be classified as re (from rectus) or si (from sinister), according to the sequence rule. If the substituents viewed from a particular face appear clockwise in order of decreasing priority, then that face is re if coimter-clockwise, then si. The re and si faces of acetaldehyde are shown below. 

A class of enzymes that catalyze the interconversion of one enantiomer with its mirror image. Care must be exercised in applying this term. For example, the enzyme that interconverts D-methyhnalonyl-CoA to L-meth-ylmalonyl-CoA is not a racemase, but is instead an epi-merase the two coenzyme A derivatives are diastereo-isomeric, and not enantiomeric, with respect to each other. 

Reactant conversion into its mirror image, NARCISSISTIC REACTION REACTING BOND RULES REACTING ENZYME CENTRIFUGATION REACTION COORDINATE DIAGRAM POTENTIAL ENERGY DIAGRAM SADDLE POINT... 

The pKa of 6.2 has been associated with the amino-terminal proline l.172 4-Oxalocrotonate tautomerase is one of a small group of enzymes that have been synthesized nonenzymatically with both l amino acids and as a mirror image constructed with d amino acids.173... 

Prochiral molecule. A nonchiral molecule that may react with an enzyme so that two groups that have a mirror image relationship to each other are treated differently. 

The stereodivergent action of DHAP aldolases is also preparatively useful under conditions of thermodynamic control [202,230, 294]. Starting from racemic 3-hydroxybutanal 84 the enantiocomplementary nature of the FruA RhuA enzyme couple will extend to the selection of the dependent stereocenter at C-6 to yield the corresponding mirror imaged products 78 with high selectivity [189], Conversely, the FucA will contribute a different major diastereomer 173, albeit only at a low de because of more balanced energetic relations [362],... 

Recall from Section 1.9 that some molecules can exist as chiral enantiomers that are mirror images of each other. Although enantiomers may appear to be superficially identical, they may differ markedly in their metabolism and toxic effects. Much of what is known about this aspect of xenobiotics has been learned from studies of the metabolism and effects of pharmaceuticals. For example, one of the two enantiomers that comprise antiepileptic Mesantoin is much more rapidly hydroxylated in the body and eliminated than is the other enantiomer. The human cytochrome P-450 enzyme denoted CYP2D6 is strongly inhibited by quinidine, but is little affected by quinine, an optical isomer of quinidine. Cases are known in which a chiral secondary alcohol is oxidized to an achiral ketone, and then reduced back to the secondary alcohol in the opposite configuration of the initial alcohol. 

Unfortunately, enantiomeric or mirror-image nudeic adds cannot be used directly in the SELEX process because of the lack of (mirror-image) enzymes which would be needed to amplify them. 

Mirror-Image Proteins As noted in Chapter 3, The amino acid residues in protein molecules are exclusively L stereoisomers. It is not clear whether this selectivity is necessary for proper protein function or is an accident of evolution. To explore this question, Milton and colleagues (1992) published a study of an enzyme made entirely of D stereoisomers. The enzyme they chose was HIV protease, a proteolytic enzyme made by HIV that converts inactive viral pre-proteins to their active forms. 

These mirror images are different, and this difference is reflected in their biochemistry. Only the enantiomer on the left can be metabolized by the usual enzyme the one on the right is not recognized as a useful amino acid. Both are named alanine, however, or 2-aminopropanoic acid in the IUPAC system. We need a simple way to distinguish between enantiomers and to give each of them a unique name. 

Human beings are such a system so are enzymes, and the asymmetric reagents you will meet in Chapter 45. But NMR machines are not. NMR machines cannot distinguish right and left—the NMR spectra of two enantiomers are identical, for example. It is not a matter of enantiomers in the molecule in question—it has a plane of symmetry and is achiral. Nonetheless, the relationship between these two hydrogens is rather like the relationship between enantiomers (the two possible ways of colouring the Hs are enantiomers—mirror images) and so they are called enantiotopic. Enantiotopic protons appear identical in the NMR spectrum. 

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