Cobalt-carbon bond dissociation energy of coenzyme B12

Halpern, Jack; Kim, Sook Hui; Leung, T. W.

doi:10.1021/ja00338a065

Cited by 170 publications

(119 citation statements)

References 2 publications

Supporting

Mentioning

114

Contrasting

Order By: Relevance

“…Surprisingly, the simple chemical model was semiquantitatively predictive for initiation of blood clotting in vitro. Chemists have used simple mechanisms and synthetic model systems to understand reactivity of organic molecules (35) and function of enzymes (36)(37)(38)(39)(40). Chemical models have stimulated our understanding of spatiotemporal dynamics of a diverse range of nonequilibrium systems, including catalysis (41), oscillations in chemistry (3) and biology (42), oocyte development (1), and fibrillation in myocardium (43).…”

Section: Discussionmentioning

confidence: 99%

Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis

Kastrup

Runyon

Shen

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

This article demonstrates that a simple chemical model system, built by using a modular approach, may be used to predict the spatiotemporal dynamics of initiation of blood clotting in the complex network of hemostasis. Microfluidics was used to create in vitro environments that expose both the complex network and the model system to surfaces patterned with patches presenting clotting stimuli. Both systems displayed a threshold response, with clotting initiating only on isolated patches larger than a threshold size. The magnitude of the threshold patch size for both systems was described by the Damkö hler number, measuring competition of reaction and diffusion. Reaction produces activators at the patch, and diffusion removes activators from the patch. The chemical model made additional predictions that were validated experimentally with human blood plasma. These experiments show that blood can be exposed to significant amounts of clot-inducing stimuli, such as tissue factor, without initiating clotting. Overall, these results demonstrate that such chemical model systems, implemented with microfluidics, may be used to predict spatiotemporal dynamics of complex biochemical networks.complexity ͉ microfluidics ͉ networks ͉ tissue factor ͉ nonlinear

show abstract

Section: Discussionmentioning

confidence: 99%

Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis

Kastrup

Runyon

Shen

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

show abstract

“…1) and a 5 H -deoxyadenosyl radical (Halpern, 1985). The rate constant of dissociation of the CoÐC bond in these reactions is about 10 10 times that of the free coenzyme, suggesting a weakening of the CoÐC bond by interaction with the enzyme in the presence of substrate (Halpern et al, 1984;Finke & Hay, 1984;Hay & Finke, 1986). It has been proposed that this weakening is a result of steric effects (Halpern et al, 1984;Bresciani-Pahor et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

“…The rate constant of dissociation of the CoÐC bond in these reactions is about 10 10 times that of the free coenzyme, suggesting a weakening of the CoÐC bond by interaction with the enzyme in the presence of substrate (Halpern et al, 1984;Finke & Hay, 1984;Hay & Finke, 1986). It has been proposed that this weakening is a result of steric effects (Halpern et al, 1984;Bresciani-Pahor et al, 1985). However, comparison of the crystal structure of B 12r (Kra È utler et al, 1989) with that of the coenzyme (Lenhert & Hodgkin, 1961;Lenhert, 1968) reveals no major molecular distortion which would explain the observed CoÐC bond weakening.…”

Section: Introductionmentioning

confidence: 99%

Neutron Laue diffraction studies of coenzyme cob(II)alamin

Langan

Lehmann

Wilkinson

et al. 1999

Acta Crystallogr D Biol Cryst

View full text Add to dashboard Cite

Using a recently designed neutron single-crystal diffractometer utilizing a narrow-band Laue concept (LADI), diffraction data were collected from a crystal of the coenzyme cob(II)alamin (B 12r ), crystallized from a mixture of D 2 O and perdeuterated acetone. The instrument was placed at the end of a cold neutron guide at the Institute Laue Langevin (ILL, Grenoble, France), and data collection with neutrons of 1.8± 8.0 A Ê wavelength to a crystallographic resolution of 1.43 A Ê was complete after about 36 h. This compares favourably with a previous experiment utilizing the same crystal specimen, where more than four weeks were required to collect monochromatic diffraction data to about 1 A Ê resolution. Using the Laue data, the structure was solved by molecular replacement with the known X-ray crystal structure. Difference density maps revealed the atomic positions (including deuterium atoms) of seven ordered solvent water molecules and two (partially disordered) acetone molecules. These density maps were compared with corresponding maps computed with monochromatic neutron-diffraction data collected to 1.0 A Ê resolution using the same crystal specimen, as well as to maps derived from high-resolution (0.90 A Ê ) synchrotron X-ray data. In spite of the better de®nition of atomic positions in the two high-resolution maps, the 1.43 A Ê LADI maps show considerable power for the determination of the location of hydrogen and deuterium positions.

show abstract

“…The bond dissociation energy of the Co-C5′ bond is 30-33 kcal mol −1 , and in aqueous solution at 25 °C, thermolysis proceeds quite slowly with a rate constant on the order of 10 −9 s −1 , corresponding to a half-life of 22 years (10)(11)(12)(13)(14)(15). The rate of Co-C5′ homolysis is drastically increased at enzymatic sites, proceeding with a rate enhancement of approximately 10 12 (12,16).…”

mentioning

confidence: 99%

5‘-Peroxyadenosine and 5‘-Peroxyadenosylcobalamin as Intermediates in the Aerobic Photolysis of Adenosylcobalamin

Schwartz

Frey

2007

Biochemistry

View full text Add to dashboard Cite

The photolysis of adenosylcobalamin (coenzyme B 12 ) results in homolytic cleavage of the Co-C5′ bond, forming cob(II)alamin and the 5′-deoxyadenosyl radical. In the presence of molecular oxygen, it has been proposed that the primary reaction is interception of the 5′-deoxyadenosyl radical by O 2 to form adenosine-5′-aldehyde as the product (Hogenkamp, H. P. C., Ladd, J. N., and Barker, H. A. (1962) J. Biol. Chem. 237, 1950-1952. 5′-Peroxyadenosine is here found to be the initial nucleoside product of this reaction and that it decomposes to adenosine-5′-aldehyde. Evidence indicates that 5′-peroxyadenosine arises from the hydrolysis of 5′-peroxyadenosylcobalamin, with the formation of cob(III)alamin. 5′-Peroxyadenosine undergoes further decomposition to adenosine-5′-aldehyde as the major final product of aerobic photolysis, as well as to adenosine and adenine as minor products. In a cobalamin-dependent process, 5′-peroxyadenosine becomes religated to cob(III)alamin to form 5′-peroxyadenosylcobalamin, which quickly decomposes to adenosine-5′-aldehyde and cob(III)alamin. This is supported by spectrophotometric observations of both rapidly photolyzed adenosylcobalamin and of the reaction of cob(III)alamin with excess 5′-peroxyadenosine. 5′-Peroxyadenosine also slowly undergoes cobalamin-independent decomposition to adenosine-5′-aldehyde and the minor products adenosine and adenine. The present study provides a detailed description of the products initially formed when aqueous, homolytically cleaved adenosylcobalamin reacts with molecular oxygen and of the behavior of those products subsequent to photolysis.Enzymes dependent upon the vitamin B 12 -coenzyme adenosylcobalamin 1 catalyze intriguingly diverse chemical reactions, including carbon-skeleton rearrangements, reductive heteroatom eliminations, and intramolecular 1,2-migrations of heteroatomic substituents; and they proceed by mechanisms involving organic free radicals as intermediates (1,2). Adenosylcobalamin incorporates a cobalt ion in an octahedral arrangement with the pyrroline and pyrrolidine groups of a corrin ring system making up the equatorial ligands, the nitrogen from a dimethylbenzimidazole moiety as the lower axial ligand, and a 5′-deoxadenosyl moiety forming a cobalt-carbon (Co-C5′) bond in the sixth, upper axial ligand position (3).The key to the function of adenosylcobalamin in enzymatic catalysis is the reversible homolytic scission of the Co-C5′ bond, generating cob(II)alamin and a transiently formed 5′- †

show abstract

Cobalt-carbon bond dissociation energy of coenzyme B12

Cited by 170 publications

References 2 publications

Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis

Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis

Neutron Laue diffraction studies of coenzyme cob(II)alamin

5‘-Peroxyadenosine and 5‘-Peroxyadenosylcobalamin as Intermediates in the Aerobic Photolysis of Adenosylcobalamin

Contact Info

Product

Resources

About