Energetics of 3-oxo-delta 5-steroid isomerase: source of the catalytic power of the enzyme.
Knowledge of the partitioning of the putative dienol intermediate (2) by steroid isomerase (KSI) (Hawkinson et al. 1991), in conjunction with various steady-state kinetic parameters, allows elucidation of the detailed free energy profile for the KSI-catalyzed conversion of 5-androstene-3,17-dione (1) to 4-androstene-3,17-dione (3). This free energy profile shows four kinetically significant energy barriers (substrate binding, the two chemical steps, and dissociation of product) that must be traversed upon conversion of 1 to 3. Thus, no single step of the catalytic cycle is cleanly rate-limiting. The source of the catalytic power of KSI is discussed via comparison of the free energy profile for the KSI-catalyzed isomerization with those for the acetate-catalyzed isomerization and the aqueous reaction at pH 7. Similarities between the energetics of the KSI-catalyzed and triosephosphate isomerase catalyzed reactions are also noted.
Department of Chemistry and Biochemistry, University of Maryland Baltimore County 21228-5398.
D C
DC
Hawkinson
T C
TC
Eames
R M
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Pollack
D000735:Androstenedione / Q000378:metabolism; D002151:Calorimetry; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D011549:Pseudomonas / Q000201:enzymology; D013251:Steroid Isomerases / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
D000735:Androstenedione; D013251:Steroid Isomerases; C022660:steroid delta-isomerase