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Cob(I)alamin reacts with sucralose to afford an alkylcobalamin: Relevance to in vivo cobalamin and sucralose interaction
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
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2011 (English)In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 49, no 4, 750-757 p.Article in journal (Refereed) Published
Abstract [en]

Vitamin B(12), viz., cyano- or hydroxo-cobalamin, can be chemically or enzymatically converted into the derivatives methyl- and adenosyl-cobalamin, which are complex organometallic cofactors associated with several cobalamin-dependent enzymes. The reduced form of vitamin B(12), cob(I)alamin {Cbl(I)}, obtained by reduction of hydroxocobalamin (OH-Cbl) with e.g. sodium borohydride, is one of the most powerful nucleophiles known. Cbl(I) was shown to react readily with the synthetic sweetener sucralose (1,6-dichloro-1,6-dideoxy-β-d-fructofuranosyl-4-chloro-4-deoxy-α-d-galactopyranoside) in an aqueous system to form an alkylcobalamin (Suc-Cbl). This occurred by replacement of one of the three chlorine atoms of sucralose with a cobalamin moiety. The efficiency of trapping sucralose in presence of excess Cbl(I) was estimated to be >90%. Furthermore, in an in vitro study using human liver S9 with NADPH regeneration, in presence of OH-Cbl and sucralose, Suc-Cbl was shown to be formed. The Suc-Cbl was characterized primarily by LC-ESI(+)-MS/MS. Given the human consumption of sucralose from food and beverages, such a reaction between the sweetener and reduced vitamin B(12) could occur in vivo.

Place, publisher, year, edition, pages
2011. Vol. 49, no 4, 750-757 p.
Keyword [en]
Vitamin B12; Sucralose; NADPH; Alkylcobalamin; LC-MS/MS
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:su:diva-53222DOI: 10.1016/j.fct.2010.11.037ISI: 000289136100006PubMedID: 21130828OAI: oai:DiVA.org:su-53222DiVA: diva2:390190
Available from: 2011-01-21 Created: 2011-01-21 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Cob(I)alamin as a Quantitative Tool for Analysis, Metabolism and Toxicological Studies of Electrophilic Compounds: Butadiene Epoxides, Glycidamide and Sucralose
Open this publication in new window or tab >>Cob(I)alamin as a Quantitative Tool for Analysis, Metabolism and Toxicological Studies of Electrophilic Compounds: Butadiene Epoxides, Glycidamide and Sucralose
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Vitamin B12 can be reduced to cob(I)alamin [Cbl(I)], which is one of the most powerful nucleophiles known and referred to as a “supernucleophile”. Cbl(I) was applied as a tool in toxicological studies of the air pollutant 1,3-butadiene (BD), the toxicant acrylamide (AA) present in many foods, and the artificial sweetener sucralose.

BD, a human carcinogen, is metabolised to genotoxic epoxides, two monoepoxides and the most potent diepoxybutane (DEB). AA, classified as a probable human carcinogen, is metabolised to the genotoxic epoxide glycidamide (GA). Due to their reactivity, quantitative analysis of the epoxides presents an analytical challenge. By using Cbl(I) for trapping, a sensitive and accurate method to quantify the epoxides as alkylcobalamins by LC-MS/MS in metabolism studies was developed and validated.

Using the Cbl(I) method, enzyme kinetic parameters, Vmax and Km, were determined for the metabolic steps associated with the BD epoxides and with the formation of GA from AA, in liver S9 fractions of human, mouse and rat.

An approach to estimate dose in vivo (i.e. area under concentration time curve, AUC) of BD epoxides by scaling the enzyme kinetic data was designed. The AUCs obtained from in vitro were evaluated by comparing with AUCs in vivo that were calculated from published haemoglobin adduct data. The AUCs from in vitro and in vivo showed to be in agreement with each other for mouse and rat, and this evaluation allowed prediction of the unknown AUC of DEB in human from BD exposure. This approach has a potential to reduce animal experiments in the future.

Sucralose is of concern due to its chlorinated structure and persistence in the aquatic environment. It was demonstrated that Cbl(I) reacts with sucralose, also under in vitro physiological conditions, which might have toxicological significance. The demonstrated reaction also suggested a potential role for Cbl(I) in dehalogenation/degradation of sucralose. This was evaluated and shown possible using heptamethyl cobyrinate, a model compound for cobalamin.

Place, publisher, year, edition, pages
Stockholm: Department of Materials and Environmental Chemistry, Stockholm University, 2011. 64 p.
National Category
Environmental Sciences
Research subject
Environmental Chemistry
Identifiers
urn:nbn:se:su:diva-55481 (URN)978-91-7447-242-4 (ISBN)
Public defence
2011-04-14, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
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Note
At the time of the doctoral defense, the following papers were unpublished  and had a status as follows: Paper 2: Submitted. Paper 3: Submitted. Paper 5: Submitted.Available from: 2011-03-23 Created: 2011-03-16 Last updated: 2011-03-17Bibliographically approved

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