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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2014-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2014/215783 |
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| author | Valerie Walker Graham A. Mills |
| author_facet | Valerie Walker Graham A. Mills |
| author_sort | Valerie Walker |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-fe1b99f4157345b6b13f0820ef1764c8 |
| institution | Kabale University |
| issn | 2356-6140 1537-744X |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
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| series | The Scientific World Journal |
| spelling | doaj-art-fe1b99f4157345b6b13f0820ef1764c82025-08-20T03:25:46ZengWileyThe 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 |
| 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 |
| 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 |
| url | http://dx.doi.org/10.1155/2014/215783 |
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