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2-Pentanone Production from Hexanoic Acid by Penicillium roqueforti from Blue Cheese: Is This the Pathway Used in Humans?

Production of 2-pentanone, a methylketone, is increased in fasting ketotic humans. Its origin is unknown. We hypothesised that it is formed via β-oxidation of hexanoic acid by the peroxisomal pathway proposed for methylketone-producing fungi and yeasts. We used Penicillium roqueforti cultured on fat...

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Autores principales: Walker, Valerie, Mills, Graham A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985342/
https://www.ncbi.nlm.nih.gov/pubmed/25143966
http://dx.doi.org/10.1155/2014/215783
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author Walker, Valerie
Mills, Graham A.
author_facet Walker, Valerie
Mills, Graham A.
author_sort Walker, Valerie
collection PubMed
description Production of 2-pentanone, a methylketone, is increased in fasting ketotic humans. Its origin is unknown. We hypothesised that it is formed via β-oxidation of hexanoic acid by the peroxisomal pathway proposed for methylketone-producing fungi and yeasts. We used Penicillium roqueforti cultured on fat (margarine) to investigate 2-pentanone production. Headspace gas of incubates of the mould with a range of substrates was analysed using solid-phase microextraction with gas chromatography-mass spectrometry. Consistent with the proposed pathway, 2-pentanone was formed from hexanoic acid, hexanoyl-CoA, hexanoylcarnitine, and ethyl-3-oxohexanoic acid but not from ethylhexanoic, 2-ethylhexanoic, octanoic, or myristic acids, octanoylcarnitine, or pentane. However, the products from deuterated (D) hexanoic-D(11) acid and hexanoic-2, 2-D(2) acid were 9D- and 2D-2-pentanone, respectively, and not 8D- and 1D-2-pentanone as predicted. When incubated under (18)O(2)/(14)N(2), there was only a very small enrichment of [(16)O(2)]- with [(18)O(2)]-containing 2-pentanone. These are new observations. They could be explained if hydrogen ions removed from hexanoyl-CoA by acyl-CoA oxidase at the commencement of β-oxidation were cycled through hydrogen peroxide and reentered the pathway through hydration of hexenoyl-CoA. This would protect other proteins from oxidative damage. Formation of 2-pentanone through a β-oxidation cycle similar to Penicillium roqueforti would be consistent with observations in humans.
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spelling pubmed-39853422014-08-20 2-Pentanone Production from Hexanoic Acid by Penicillium roqueforti from Blue Cheese: Is This the Pathway Used in Humans? Walker, Valerie Mills, Graham A. ScientificWorldJournal Research Article Production of 2-pentanone, a methylketone, is increased in fasting ketotic humans. Its origin is unknown. We hypothesised that it is formed via β-oxidation of hexanoic acid by the peroxisomal pathway proposed for methylketone-producing fungi and yeasts. We used Penicillium roqueforti cultured on fat (margarine) to investigate 2-pentanone production. Headspace gas of incubates of the mould with a range of substrates was analysed using solid-phase microextraction with gas chromatography-mass spectrometry. Consistent with the proposed pathway, 2-pentanone was formed from hexanoic acid, hexanoyl-CoA, hexanoylcarnitine, and ethyl-3-oxohexanoic acid but not from ethylhexanoic, 2-ethylhexanoic, octanoic, or myristic acids, octanoylcarnitine, or pentane. However, the products from deuterated (D) hexanoic-D(11) acid and hexanoic-2, 2-D(2) acid were 9D- and 2D-2-pentanone, respectively, and not 8D- and 1D-2-pentanone as predicted. When incubated under (18)O(2)/(14)N(2), there was only a very small enrichment of [(16)O(2)]- with [(18)O(2)]-containing 2-pentanone. These are new observations. They could be explained if hydrogen ions removed from hexanoyl-CoA by acyl-CoA oxidase at the commencement of β-oxidation were cycled through hydrogen peroxide and reentered the pathway through hydration of hexenoyl-CoA. This would protect other proteins from oxidative damage. Formation of 2-pentanone through a β-oxidation cycle similar to Penicillium roqueforti would be consistent with observations in humans. Hindawi Publishing Corporation 2014 2014-03-27 /pmc/articles/PMC3985342/ /pubmed/25143966 http://dx.doi.org/10.1155/2014/215783 Text en Copyright © 2014 V. Walker and G. A. Mills. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Walker, Valerie
Mills, Graham A.
2-Pentanone Production from Hexanoic Acid by Penicillium roqueforti from Blue Cheese: Is This the Pathway Used in Humans?
title 2-Pentanone Production from Hexanoic Acid by Penicillium roqueforti from Blue Cheese: Is This the Pathway Used in Humans?
title_full 2-Pentanone Production from Hexanoic Acid by Penicillium roqueforti from Blue Cheese: Is This the Pathway Used in Humans?
title_fullStr 2-Pentanone Production from Hexanoic Acid by Penicillium roqueforti from Blue Cheese: Is This the Pathway Used in Humans?
title_full_unstemmed 2-Pentanone Production from Hexanoic Acid by Penicillium roqueforti from Blue Cheese: Is This the Pathway Used in Humans?
title_short 2-Pentanone Production from Hexanoic Acid by Penicillium roqueforti from Blue Cheese: Is This the Pathway Used in Humans?
title_sort 2-pentanone production from hexanoic acid by penicillium roqueforti from blue cheese: is this the pathway used in humans?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985342/
https://www.ncbi.nlm.nih.gov/pubmed/25143966
http://dx.doi.org/10.1155/2014/215783
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