Kinetic Isotope Effects on the Rate-Limiting Step of Heme Oxygenase Catalysis Indicate Concerted Proton Transfer/Heme Hydroxylation

2003 ◽  
Vol 125 (52) ◽  
pp. 16208-16209 ◽  
Author(s):  
Roman Davydov ◽  
Toshitaka Matsui ◽  
Hiroshi Fujii ◽  
Masao Ikeda-Saito ◽  
Brian M. Hoffman
Keyword(s):  
Proton Transfer ◽  
Heme Oxygenase ◽  
Isotope Effects ◽  
Kinetic Isotope Effects ◽  
Kinetic Isotope ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

scholarly journals Comment on “Topography of the free energy landscape of Claisen–Schmidt condensation: solvent and temperature effects on the rate-controlling step” by N. D. Coutinho, H. G. Machado, V. H. Carvalho-Silva and W. A. da Silva, Phys. Chem. Chem. Phys., 2021, 23, 6738

2021 ◽  
Vol 23 (38) ◽  
pp. 22199-22201
Author(s):  
Charles L. Perrin
Keyword(s):  
Temperature Effects ◽  
Isotope Effects ◽  
Energy Landscape ◽  
Kinetic Isotope Effects ◽  
Chem Phys ◽  
Kinetic Isotope ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting ◽  
Rate Controlling Step

The referenced article in PCCP presents calculations of solvent kinetic isotope effects that indicate that the rate-limiting step in base-catalyzed chalcone formation in aqueous solution becomes the second enolization.

scholarly journals Substrate-Dependent Sensitivity of SIRT1 to Nicotinamide Inhibition

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 312
Author(s):  
Stacia Rymarchyk ◽  
Wenjia Kang ◽  
Yana Cen
Keyword(s):  
Proton Transfer ◽  
Isotope Effects ◽  
Negative Regulator ◽  
Base Exchange ◽  
Glucose And Lipid Metabolism ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Catalyzed Reactions ◽  
Solvent Isotope ◽  
Rate Limiting

SIRT1 is the most extensively studied human sirtuin with a broad spectrum of endogenous targets. It has been implicated in the regulation of a myriad of cellular events, such as gene transcription, mitochondria biogenesis, insulin secretion as well as glucose and lipid metabolism. From a mechanistic perspective, nicotinamide (NAM), a byproduct of a sirtuin-catalyzed reaction, reverses a reaction intermediate to regenerate NAD+ through “base exchange”, leading to the inhibition of the forward deacetylation. NAM has been suggested as a universal sirtuin negative regulator. Sirtuins have evolved different strategies in response to NAM regulation. Here, we report the detailed kinetic analysis of SIRT1-catalyzed reactions using endogenous substrate-based synthetic peptides. A novel substrate-dependent sensitivity of SIRT1 to NAM inhibition was observed. Additionally, SIRT1 demonstrated pH-dependent deacetylation with normal solvent isotope effects (SIEs), consistent with proton transfer in the rate-limiting step. Base exchange, in contrast, was insensitive to pH changes with no apparent SIEs, indicative of lack of proton transfer in the rate-limiting step. Consequently, NAM inhibition was attenuated at a high pH in proteated buffers. Our study provides new evidence for “activation by de-repression” as an effective sirtuin activation strategy.

scholarly journals Heavy-Enzyme Kinetic Isotope Effects on Proton Transfer in Alanine Racemase

2013 ◽  
Vol 135 (7) ◽  
pp. 2509-2511 ◽  
Author(s):  
Michael D. Toney ◽  
Joan Nieto Castro ◽  
Trevor A. Addington
Keyword(s):  
Proton Transfer ◽  
Isotope Effects ◽  
Kinetic Isotope Effects ◽  
Alanine Racemase ◽  
Enzyme Kinetic ◽  
Kinetic Isotope

Kinetic Isotope Effects in Multiple Proton Transfer

2005 ◽  
pp. 521-548 ◽  
Author(s):  
Willem Siebrand ◽  
Zorka Smedarchina ◽  
Antonio Fernández-Ramos
Keyword(s):  
Proton Transfer ◽  
Isotope Effects ◽  
Kinetic Isotope Effects ◽  
Kinetic Isotope
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