Pulse Radiolysis Studies on the Reaction of the Reduced Vitamin B<sub>12</sub> Complex Cob(II)alamin with Superoxide

Dassanayake, Rohan S.; Cabelli, Diane E.; Brasch, Nicola E.

doi:10.1002/cbic.201300229

Cited by 11 publications

(5 citation statements)

References 28 publications

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“…Cobalamin(II) has been shown to react with O 2 · − at a rate two times faster than we found for Cbi(II) [( 13 ) and Table 1 ], but to our knowledge, the reaction of cobalamin(III) with O 2 · − has not been reported. We found that cobalamin(III) reacts with O 2 · − , but at a rate less than one-tenth that of Cbi(III) (Figure S1C, D, Table 1 ).…”

Section: Resultscontrasting

confidence: 47%

“…We wanted to compare cobinamide to similar agents, and chose cobalamin, imisopasem, and MnTBAP for the following reasons. Cobalamin is structurally similar to cobinamide, cobalamin(II) reacts readily with O 2 · − and ONOO − , both cobalamin(II) and cobalamin(III) react with hydrogen peroxide, and cobalamin has antioxidant effects in several in-vivo systems [Table 1 ; ( 13 , 14 , 17 , 19–21 )]. Imisopasem and MnTBAP are SOD mimetics, with imisopasem having a relatively high reaction rate with O 2 · − , and MnTBAP additionally reacts with ONOO − ; both agents have been used extensively in cells and animals ( 24–32 ) (Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…Cyanide and sulfide inhibit cytochrome c oxidase in complex IV of the mitochondrial electron transport chain, thereby generating superoxide (O 2 · − ) and inducing intracellular oxidative stress ( 10 , 12 ). Cobalamin with the cobalt in the +2 oxidation state reacts with O 2 · − , peroxynitrite (ONOO − ), and hypochlorous acid, and in both the +3 and +2 oxidation states with hydrogen peroxide (H 2 O 2 ) and the carbonate radical anion (CO 3 · − ) ( 13–18 ). Consistent with these in-vitro data, cobalamin functions as an antioxidant in several cell and animal models ( 19–23 ).…”

Section: Introductionmentioning

confidence: 99%

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Cobinamide is a strong and versatile antioxidant that overcomes oxidative stress in cells, flies, and diabetic mice

et al. 2022

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Increased oxidative stress underlies a variety of diseases, including diabetes. Here we show that the cobalamin/vitamin B12 analog cobinamide is a strong and multi-faceted antioxidant, neutralizing superoxide, hydrogen peroxide, and peroxynitrite, with apparent rate constants of 1.9 × 108, 3.7 × 104, and 6.3 × 106 M−1 s−1, respectively for cobinamide with the cobalt in the + 2 oxidation state. Cobinamide with the cobalt in the + 3 oxidation state yielded apparent rate constants of 1.1 × 108 and 8.0 × 102 M−1 s−1 for superoxide and hydrogen peroxide, respectively. In mammalian cells and Drosophila melanogaster, cobinamide outperformed cobalamin and two well-known antioxidants, imisopasem manganese and manganese(III)tetrakis(4-benzoic acid)porphyrin, in reducing oxidative stress as evidenced by: (i) decreased mitochondrial superoxide and return of the mitochondrial membrane potential in rotenone- and antimycin A-exposed H9c2 rat cardiomyocytes; (ii) reduced JNK phosphorylation in hydrogen-peroxide-treated H9c2 cells; (iii) increased growth in paraquat-exposed COS-7 fibroblasts; and (iv) improved survival in paraquat-treated flies. In diabetic mice, cobinamide administered in the animals’ drinking water completely prevented an increase in lipid and protein oxidation, DNA damage, and fibrosis in the heart. Cobinamide is a promising new antioxidant that has potential use in diseases with heightened oxidative stress.

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Section: Resultscontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cobinamide is a strong and versatile antioxidant that overcomes oxidative stress in cells, flies, and diabetic mice

et al. 2022

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“…The central cobalt can change its oxidation state between +3 (cob(III)alamin), +2 (cob(II)alamin), and +1(cob(I)alamin), which makes these compounds redox active. Moreover, it has been shown that Cbl reacts with O 2 •− at rates comparable with that of superoxide dismutase [ 79 , 80 ]. Hence, it has been suggested that cobalamins modulate inflammation and redox status [ 81 – 83 ] in addition to and independently of their cofactor function.…”

Section: Micronutrientsmentioning

confidence: 99%

Insights on Localized and Systemic Delivery of Redox‐Based Therapeutics

Buglak

Batrakova

Mota

et al. 2018

Oxidative Medicine and Cellular Longevity

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Reactive oxygen and nitrogen species are indispensable in cellular physiology and signaling. Overproduction of these reactive species or failure to maintain their levels within the physiological range results in cellular redox dysfunction, often termed cellular oxidative stress. Redox dysfunction in turn is at the molecular basis of disease etiology and progression. Accordingly, antioxidant intervention to restore redox homeostasis has been pursued as a therapeutic strategy for cardiovascular disease, cancer, and neurodegenerative disorders among many others. Despite preliminary success in cellular and animal models, redox-based interventions have virtually been ineffective in clinical trials. We propose the fundamental reason for their failure is a flawed delivery approach. Namely, systemic delivery for a geographically local disease limits the effectiveness of the antioxidant. We take a critical look at the literature and evaluate successful and unsuccessful approaches to translation of redox intervention to the clinical arena, including dose, patient selection, and delivery approach. We argue that when interpreting a failed antioxidant-based clinical trial, it is crucial to take into account these variables and importantly, whether the drug had an effect on the redox status. Finally, we propose that local and targeted delivery hold promise to translate redox-based therapies from the bench to the bedside.

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“…[3, 14a,c,d] Vitamin B 12 derivatives, also knowna sc obalamins (Cbls), Figure 1, are essential cofactors for mammalian methionine synthasea nd mitochondrial methylmalonyl-CoA mutase. [15] Like porphyrins, the metal center of reduced cobalaminsisr apidly oxidized by ROS/RNS, including superoxide, [16,17] nitric oxide, [18] peroxynitrite, [19] nitrogen dioxide, [20] and nitrite. [21] Furthermore ROS such as NO inactivate methionine synthase and methylmalonyl-CoA mutase.…”

Section: Introductionmentioning

confidence: 99%

Pulse Radiolysis and Ultra‐High‐Performance Liquid Chromatography/High‐Resolution Mass Spectrometry Studies on the Reactions of the Carbonate Radical with Vitamin B₁₂ Derivatives

Dassanayake

Shelley

Cabelli

et al. 2015

Chemistry A European J

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The reactions of the carbonate radical anion (CO3 (.) (-) ) with vitamin B12 derivatives were studied by pulse radiolysis. The carbonate radical anion directly oxidizes the metal center of cob(II)alamin quantitively to give hydroxycobalamin, with a bimolecular rate constant of 2.0×10(9) M(-1) s(-1) . The reaction of CO3 (.) (-) with hydroxycobalamin proceeds in two steps. The second-order rate constant for the first reaction is 4.3×10(8) M(-1) s(-1) . The rate of the second reaction is independent of the hydroxycobalamin concentration and is approximately 3.0×10(3) s(-1) . Evidence for formation of corrinoid complexes differing from cobalamin by the abstraction of two or four hydrogen atoms from the corrin macrocycle and lactone ring formation has been obtained by ultra-high-performance liquid chromatography/high-resolution mass spectrometry (UHPLC/HRMS). A mechanism is proposed in which abstraction of a hydrogen atom by CO3 (.) (-) from a carbon atom not involved in the π conjugation system of the corrin occurs in the first step, resulting in formation of a Co(III) C-centered radical that undergoes rapid intramolecular electron transfer to form the corresponding Co(II) carbocation complex for about 50 % of these complexes. Subsequent competing pathways lead to formation of corrinoid complexes with two fewer hydrogen atoms and lactone derivatives of B12 . Our results demonstrate the potential of UHPLC combined with HRMS in the separation and identification of tetrapyrrole macrocycles with minor modifications from their parent molecule.

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Pulse Radiolysis Studies on the Reaction of the Reduced Vitamin B₁₂ Complex Cob(II)alamin with Superoxide

Cited by 11 publications

References 28 publications

Cobinamide is a strong and versatile antioxidant that overcomes oxidative stress in cells, flies, and diabetic mice

Cobinamide is a strong and versatile antioxidant that overcomes oxidative stress in cells, flies, and diabetic mice

Insights on Localized and Systemic Delivery of Redox‐Based Therapeutics

Pulse Radiolysis and Ultra‐High‐Performance Liquid Chromatography/High‐Resolution Mass Spectrometry Studies on the Reactions of the Carbonate Radical with Vitamin B₁₂ Derivatives

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Pulse Radiolysis Studies on the Reaction of the Reduced Vitamin B12 Complex Cob(II)alamin with Superoxide

Cited by 11 publications

References 28 publications

Cobinamide is a strong and versatile antioxidant that overcomes oxidative stress in cells, flies, and diabetic mice

Cobinamide is a strong and versatile antioxidant that overcomes oxidative stress in cells, flies, and diabetic mice

Insights on Localized and Systemic Delivery of Redox‐Based Therapeutics

Pulse Radiolysis and Ultra‐High‐Performance Liquid Chromatography/High‐Resolution Mass Spectrometry Studies on the Reactions of the Carbonate Radical with Vitamin B12 Derivatives

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Product

Resources

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Pulse Radiolysis Studies on the Reaction of the Reduced Vitamin B₁₂ Complex Cob(II)alamin with Superoxide

Pulse Radiolysis and Ultra‐High‐Performance Liquid Chromatography/High‐Resolution Mass Spectrometry Studies on the Reactions of the Carbonate Radical with Vitamin B₁₂ Derivatives