Cargando…

A dodecylamine derivative of cyanocobalamin potently inhibits the activities of cobalamin-dependent methylmalonyl-CoA mutase and methionine synthase of Caenorhabditis elegans

In this study, we showed that cyanocobalamin dodecylamine, a ribose 5′-carbamate derivative of cyanocobalamin, was absorbed and accumulated to significant levels by Caenorhabditis elegans and was not further metabolized. The levels of methylmalonic acid and homocysteine, which serve as indicators of...

Descripción completa

Detalles Bibliográficos
Autores principales: Bito, Tomohiro, Yabuta, Yukinori, Ichiyanagi, Tsuyoshi, Kawano, Tsuyoshi, Watanabe, Fumio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141197/
https://www.ncbi.nlm.nih.gov/pubmed/25161880
http://dx.doi.org/10.1016/j.fob.2014.07.008
_version_ 1782331611581251584
author Bito, Tomohiro
Yabuta, Yukinori
Ichiyanagi, Tsuyoshi
Kawano, Tsuyoshi
Watanabe, Fumio
author_facet Bito, Tomohiro
Yabuta, Yukinori
Ichiyanagi, Tsuyoshi
Kawano, Tsuyoshi
Watanabe, Fumio
author_sort Bito, Tomohiro
collection PubMed
description In this study, we showed that cyanocobalamin dodecylamine, a ribose 5′-carbamate derivative of cyanocobalamin, was absorbed and accumulated to significant levels by Caenorhabditis elegans and was not further metabolized. The levels of methylmalonic acid and homocysteine, which serve as indicators of cobalamin deficiency, were significantly increased in C. elegans treated with the dodecylamine derivative, indicating severe cobalamin deficiency. Kinetic studies show that the affinity of the cyanocobalamin dodecylamine derivative was greater for two cobalamin-dependent enzymes, methylmalonyl-CoA mutase and methionine synthase, compared with their respective coenzymes, suggesting that the dodecylamine derivative inactivated these enzymes. The dodecylamine derivative did not affect the levels of mRNAs encoding these enzymes or those of other proteins involved in intercellular cobalamin metabolism, including methylmalonyl-CoA mutase (mmcm-1), methylmalonic acidemia cobalamin A complementation group (mmaa-1), methylmalonic aciduria cblC type (cblc-1), and methionine synthase reductase (mtrr-1). In contrast, the level of the mRNAs encoding cob(I)alamin adenosyltransferase (mmab-1) was increased significantly and identical to that of cobalamin-deficient C. elegans. These results indicate that the cyanocobalamin-dodecylamine derivative acts as a potent inhibitor of cobalamin-dependent enzymes and induces severe cobalamin deficiency in C. elegans.
format Online
Article
Text
id pubmed-4141197
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-41411972014-08-26 A dodecylamine derivative of cyanocobalamin potently inhibits the activities of cobalamin-dependent methylmalonyl-CoA mutase and methionine synthase of Caenorhabditis elegans Bito, Tomohiro Yabuta, Yukinori Ichiyanagi, Tsuyoshi Kawano, Tsuyoshi Watanabe, Fumio FEBS Open Bio Article In this study, we showed that cyanocobalamin dodecylamine, a ribose 5′-carbamate derivative of cyanocobalamin, was absorbed and accumulated to significant levels by Caenorhabditis elegans and was not further metabolized. The levels of methylmalonic acid and homocysteine, which serve as indicators of cobalamin deficiency, were significantly increased in C. elegans treated with the dodecylamine derivative, indicating severe cobalamin deficiency. Kinetic studies show that the affinity of the cyanocobalamin dodecylamine derivative was greater for two cobalamin-dependent enzymes, methylmalonyl-CoA mutase and methionine synthase, compared with their respective coenzymes, suggesting that the dodecylamine derivative inactivated these enzymes. The dodecylamine derivative did not affect the levels of mRNAs encoding these enzymes or those of other proteins involved in intercellular cobalamin metabolism, including methylmalonyl-CoA mutase (mmcm-1), methylmalonic acidemia cobalamin A complementation group (mmaa-1), methylmalonic aciduria cblC type (cblc-1), and methionine synthase reductase (mtrr-1). In contrast, the level of the mRNAs encoding cob(I)alamin adenosyltransferase (mmab-1) was increased significantly and identical to that of cobalamin-deficient C. elegans. These results indicate that the cyanocobalamin-dodecylamine derivative acts as a potent inhibitor of cobalamin-dependent enzymes and induces severe cobalamin deficiency in C. elegans. Elsevier 2014-08-01 /pmc/articles/PMC4141197/ /pubmed/25161880 http://dx.doi.org/10.1016/j.fob.2014.07.008 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Bito, Tomohiro
Yabuta, Yukinori
Ichiyanagi, Tsuyoshi
Kawano, Tsuyoshi
Watanabe, Fumio
A dodecylamine derivative of cyanocobalamin potently inhibits the activities of cobalamin-dependent methylmalonyl-CoA mutase and methionine synthase of Caenorhabditis elegans
title A dodecylamine derivative of cyanocobalamin potently inhibits the activities of cobalamin-dependent methylmalonyl-CoA mutase and methionine synthase of Caenorhabditis elegans
title_full A dodecylamine derivative of cyanocobalamin potently inhibits the activities of cobalamin-dependent methylmalonyl-CoA mutase and methionine synthase of Caenorhabditis elegans
title_fullStr A dodecylamine derivative of cyanocobalamin potently inhibits the activities of cobalamin-dependent methylmalonyl-CoA mutase and methionine synthase of Caenorhabditis elegans
title_full_unstemmed A dodecylamine derivative of cyanocobalamin potently inhibits the activities of cobalamin-dependent methylmalonyl-CoA mutase and methionine synthase of Caenorhabditis elegans
title_short A dodecylamine derivative of cyanocobalamin potently inhibits the activities of cobalamin-dependent methylmalonyl-CoA mutase and methionine synthase of Caenorhabditis elegans
title_sort dodecylamine derivative of cyanocobalamin potently inhibits the activities of cobalamin-dependent methylmalonyl-coa mutase and methionine synthase of caenorhabditis elegans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141197/
https://www.ncbi.nlm.nih.gov/pubmed/25161880
http://dx.doi.org/10.1016/j.fob.2014.07.008
work_keys_str_mv AT bitotomohiro adodecylaminederivativeofcyanocobalaminpotentlyinhibitstheactivitiesofcobalamindependentmethylmalonylcoamutaseandmethioninesynthaseofcaenorhabditiselegans
AT yabutayukinori adodecylaminederivativeofcyanocobalaminpotentlyinhibitstheactivitiesofcobalamindependentmethylmalonylcoamutaseandmethioninesynthaseofcaenorhabditiselegans
AT ichiyanagitsuyoshi adodecylaminederivativeofcyanocobalaminpotentlyinhibitstheactivitiesofcobalamindependentmethylmalonylcoamutaseandmethioninesynthaseofcaenorhabditiselegans
AT kawanotsuyoshi adodecylaminederivativeofcyanocobalaminpotentlyinhibitstheactivitiesofcobalamindependentmethylmalonylcoamutaseandmethioninesynthaseofcaenorhabditiselegans
AT watanabefumio adodecylaminederivativeofcyanocobalaminpotentlyinhibitstheactivitiesofcobalamindependentmethylmalonylcoamutaseandmethioninesynthaseofcaenorhabditiselegans
AT bitotomohiro dodecylaminederivativeofcyanocobalaminpotentlyinhibitstheactivitiesofcobalamindependentmethylmalonylcoamutaseandmethioninesynthaseofcaenorhabditiselegans
AT yabutayukinori dodecylaminederivativeofcyanocobalaminpotentlyinhibitstheactivitiesofcobalamindependentmethylmalonylcoamutaseandmethioninesynthaseofcaenorhabditiselegans
AT ichiyanagitsuyoshi dodecylaminederivativeofcyanocobalaminpotentlyinhibitstheactivitiesofcobalamindependentmethylmalonylcoamutaseandmethioninesynthaseofcaenorhabditiselegans
AT kawanotsuyoshi dodecylaminederivativeofcyanocobalaminpotentlyinhibitstheactivitiesofcobalamindependentmethylmalonylcoamutaseandmethioninesynthaseofcaenorhabditiselegans
AT watanabefumio dodecylaminederivativeofcyanocobalaminpotentlyinhibitstheactivitiesofcobalamindependentmethylmalonylcoamutaseandmethioninesynthaseofcaenorhabditiselegans