Structure-activity correlations in human kidney aldehyde reductase-catalyzed reduction of para-substituted benzaldehyde by 3-acetyl pyridine adenine dinucleotide phosphate

Aruni Bhatnagar, Si Qi Liu, Satish Srivastava

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Abstract

Steady-state kinetic parameters of the human kidney aldehyde reductase-catalyzed reduction of para-substituted benzaldehydes by 3-acetyl pyridine dinucleotide phosphate (3-APADPH) were determined. The kcat of aldehyde reduction by 3-APADPH was 2- to 4-fold lower than by NADPH. The dissociation constant of 3-APADPH from the enzyme-coenzyme complex was higher (77 μM) than that of NADPH (5.3 μM). Primary deuterium kinetic isotope effects on both kcat and kcat/Km for para-substituted benzaldehyde reduction by 3-APADPH (with the exception of para-carboxybenzaldehyde) were equal and on average 2.82 ± 0.21, suggesting that these reactions follow a rapid equilibrium-ordered reaction scheme in which the hydride transfer step is rate-limiting. Multiple regression analysis of the data suggests that benzaldehyde reduction depends upon electronic substituent effects, characterized by a ρ{variant} value of 0.5. These data are consistent with a transition state in which the charge on the aldehyde carbonyl increases relative to the charge on this group in the ground state. A positive deviation of para-carboxybenzaldehyde from the linear correlation between other benzaldehydes and the substituent constant σ+ suggests a specific interaction of the carboxyl substituent of the substrate with the enzyme.

Original languageEnglish (US)
Pages (from-to)180-186
Number of pages7
JournalBiochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
Volume1077
Issue number2
DOIs
StatePublished - Apr 8 1991

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Benzaldehydes
Aldehyde Reductase
Adenine
NADP
Aldehydes
Enzymes and Coenzymes
Phosphates
Kidney
Deuterium
Isotopes
Regression Analysis
Enzymes
Kinetic parameters
Regression analysis
Hydrides
Ground state
Kinetics
benzaldehyde
4-carboxybenzaladehyde
pyridine

Keywords

  • (Human kidney)
  • Aldehyde reductase
  • Enzyme kinetics
  • Hammett plot
  • Transition state

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology
  • Structural Biology

Cite this

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title = "Structure-activity correlations in human kidney aldehyde reductase-catalyzed reduction of para-substituted benzaldehyde by 3-acetyl pyridine adenine dinucleotide phosphate",
abstract = "Steady-state kinetic parameters of the human kidney aldehyde reductase-catalyzed reduction of para-substituted benzaldehydes by 3-acetyl pyridine dinucleotide phosphate (3-APADPH) were determined. The kcat of aldehyde reduction by 3-APADPH was 2- to 4-fold lower than by NADPH. The dissociation constant of 3-APADPH from the enzyme-coenzyme complex was higher (77 μM) than that of NADPH (5.3 μM). Primary deuterium kinetic isotope effects on both kcat and kcat/Km for para-substituted benzaldehyde reduction by 3-APADPH (with the exception of para-carboxybenzaldehyde) were equal and on average 2.82 ± 0.21, suggesting that these reactions follow a rapid equilibrium-ordered reaction scheme in which the hydride transfer step is rate-limiting. Multiple regression analysis of the data suggests that benzaldehyde reduction depends upon electronic substituent effects, characterized by a ρ{variant} value of 0.5. These data are consistent with a transition state in which the charge on the aldehyde carbonyl increases relative to the charge on this group in the ground state. A positive deviation of para-carboxybenzaldehyde from the linear correlation between other benzaldehydes and the substituent constant σ+ suggests a specific interaction of the carboxyl substituent of the substrate with the enzyme.",
keywords = "(Human kidney), Aldehyde reductase, Enzyme kinetics, Hammett plot, Transition state",
author = "Aruni Bhatnagar and Liu, {Si Qi} and Satish Srivastava",
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T1 - Structure-activity correlations in human kidney aldehyde reductase-catalyzed reduction of para-substituted benzaldehyde by 3-acetyl pyridine adenine dinucleotide phosphate

AU - Bhatnagar, Aruni

AU - Liu, Si Qi

AU - Srivastava, Satish

PY - 1991/4/8

Y1 - 1991/4/8

N2 - Steady-state kinetic parameters of the human kidney aldehyde reductase-catalyzed reduction of para-substituted benzaldehydes by 3-acetyl pyridine dinucleotide phosphate (3-APADPH) were determined. The kcat of aldehyde reduction by 3-APADPH was 2- to 4-fold lower than by NADPH. The dissociation constant of 3-APADPH from the enzyme-coenzyme complex was higher (77 μM) than that of NADPH (5.3 μM). Primary deuterium kinetic isotope effects on both kcat and kcat/Km for para-substituted benzaldehyde reduction by 3-APADPH (with the exception of para-carboxybenzaldehyde) were equal and on average 2.82 ± 0.21, suggesting that these reactions follow a rapid equilibrium-ordered reaction scheme in which the hydride transfer step is rate-limiting. Multiple regression analysis of the data suggests that benzaldehyde reduction depends upon electronic substituent effects, characterized by a ρ{variant} value of 0.5. These data are consistent with a transition state in which the charge on the aldehyde carbonyl increases relative to the charge on this group in the ground state. A positive deviation of para-carboxybenzaldehyde from the linear correlation between other benzaldehydes and the substituent constant σ+ suggests a specific interaction of the carboxyl substituent of the substrate with the enzyme.

AB - Steady-state kinetic parameters of the human kidney aldehyde reductase-catalyzed reduction of para-substituted benzaldehydes by 3-acetyl pyridine dinucleotide phosphate (3-APADPH) were determined. The kcat of aldehyde reduction by 3-APADPH was 2- to 4-fold lower than by NADPH. The dissociation constant of 3-APADPH from the enzyme-coenzyme complex was higher (77 μM) than that of NADPH (5.3 μM). Primary deuterium kinetic isotope effects on both kcat and kcat/Km for para-substituted benzaldehyde reduction by 3-APADPH (with the exception of para-carboxybenzaldehyde) were equal and on average 2.82 ± 0.21, suggesting that these reactions follow a rapid equilibrium-ordered reaction scheme in which the hydride transfer step is rate-limiting. Multiple regression analysis of the data suggests that benzaldehyde reduction depends upon electronic substituent effects, characterized by a ρ{variant} value of 0.5. These data are consistent with a transition state in which the charge on the aldehyde carbonyl increases relative to the charge on this group in the ground state. A positive deviation of para-carboxybenzaldehyde from the linear correlation between other benzaldehydes and the substituent constant σ+ suggests a specific interaction of the carboxyl substituent of the substrate with the enzyme.

KW - (Human kidney)

KW - Aldehyde reductase

KW - Enzyme kinetics

KW - Hammett plot

KW - Transition state

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