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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doaj-fe1b99f4157345b6b13f0820ef1764c82020-11-24T23:54:50ZengHindawi LimitedThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/2157832157832-Pentanone Production from Hexanoic Acid by Penicillium roqueforti from Blue Cheese: Is This the Pathway Used in Humans?Valerie Walker0Graham A. Mills1Department of Clinical Biochemistry, Southampton General Hospital, C level, MP 6, South Block, Tremona Road, Southampton SO16 6YD, UKSchool of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael’s Building, White Swan Road, Portsmouth PO1 2DT, UKProduction 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-D11 acid and hexanoic-2, 2-D2 acid were 9D- and 2D-2-pentanone, respectively, and not 8D- and 1D-2-pentanone as predicted. When incubated under 18O2/14N2, there was only a very small enrichment of [16O2]- with [18O2]-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.http://dx.doi.org/10.1155/2014/215783 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valerie Walker Graham A. Mills |
spellingShingle |
Valerie Walker Graham A. Mills 2-Pentanone Production from Hexanoic Acid by Penicillium roqueforti from Blue Cheese: Is This the Pathway Used in Humans? The Scientific World Journal |
author_facet |
Valerie Walker Graham A. Mills |
author_sort |
Valerie Walker |
title |
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_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_sort |
2-pentanone production from hexanoic acid by penicillium roqueforti from blue cheese: is this the pathway used in humans? |
publisher |
Hindawi Limited |
series |
The Scientific World Journal |
issn |
2356-6140 1537-744X |
publishDate |
2014-01-01 |
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-D11 acid and hexanoic-2, 2-D2 acid were 9D- and 2D-2-pentanone, respectively, and not 8D- and 1D-2-pentanone as predicted. When incubated under 18O2/14N2, there was only a very small enrichment of [16O2]- with [18O2]-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. |
url |
http://dx.doi.org/10.1155/2014/215783 |
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