Racemization of Vinylglycolate Catalyzed by Mandelate Racemase

Rongshi Li, Vincent M. Powers, George L. Kenyon, John W. Kozarich

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Vinylglycolate (2-hydroxy-3-butenoic acid, 2) has been found to be an excellent substrate of mandelate racemase. The measured steady-state kinetic parameters for the enantiomers of 2 are comparable, with a maximal racemization rate that is 35% relative to mandelate. Racemization of 2 is subject to a primary deuterium kinetic isotope of about 4, indicating that abstraction of the α-proton is at least partially rate-limiting. Although α-hydroxybutyrate (5), the saturated analogue of 2, is not a substrate, 5 competitively inhibits racemization of 2 with a Ki value comparable to the average Km value for the latter. These results implicate the importance of β,γ-unsaturation in promoting facile racemization of the substrate α-proton. In addition, the enzyme catalyzes the isomerization of 2 to α-ketobutyrate (4), with a partition ratio for racemization/isomerization of about 1 × 104. These observations highlight the precision with which mandelate racemase can promote racemization to the virtual exclusion of a thermodynamically more favored process.

Original languageEnglish (US)
Pages (from-to)3347-3351
Number of pages5
JournalJournal of Organic Chemistry
Volume60
Issue number11
DOIs
StatePublished - Jun 1 1995

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mandelate racemase
Isomerization
Protons
Substrates
Hydroxybutyrates
Enantiomers
Deuterium
Kinetic parameters
Isotopes
Kinetics
Enzymes

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Racemization of Vinylglycolate Catalyzed by Mandelate Racemase. / Li, Rongshi; Powers, Vincent M.; Kenyon, George L.; Kozarich, John W.

In: Journal of Organic Chemistry, Vol. 60, No. 11, 01.06.1995, p. 3347-3351.

Research output: Contribution to journalArticle

Li, Rongshi ; Powers, Vincent M. ; Kenyon, George L. ; Kozarich, John W. / Racemization of Vinylglycolate Catalyzed by Mandelate Racemase. In: Journal of Organic Chemistry. 1995 ; Vol. 60, No. 11. pp. 3347-3351.
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AB - Vinylglycolate (2-hydroxy-3-butenoic acid, 2) has been found to be an excellent substrate of mandelate racemase. The measured steady-state kinetic parameters for the enantiomers of 2 are comparable, with a maximal racemization rate that is 35% relative to mandelate. Racemization of 2 is subject to a primary deuterium kinetic isotope of about 4, indicating that abstraction of the α-proton is at least partially rate-limiting. Although α-hydroxybutyrate (5), the saturated analogue of 2, is not a substrate, 5 competitively inhibits racemization of 2 with a Ki value comparable to the average Km value for the latter. These results implicate the importance of β,γ-unsaturation in promoting facile racemization of the substrate α-proton. In addition, the enzyme catalyzes the isomerization of 2 to α-ketobutyrate (4), with a partition ratio for racemization/isomerization of about 1 × 104. These observations highlight the precision with which mandelate racemase can promote racemization to the virtual exclusion of a thermodynamically more favored process.

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