Enzymology of β-Oxidation of (Poly)unsaturated Fatty Acids

Novikov, D. K.; Koivuranta, Kari; Helander, Heli; Filppula, Sirpa A.; Yagi, Ahmed; Qin, Yong-Mei; Hiltunen, Kalervo

doi:10.1007/0-306-46818-2_34

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…Basal CPT1A mRNA are significantly higher in MCF7 cells compared to normal breast epithelial cell line 184B5 [51]. ECI and DECR1 participate in the catabolism of PUFA with double bonds at even and odd numbered carbon atoms [19,50,52,53]. In contrast, in HepG2 cells, ACOX1 was highly expressed; it is the enzyme which catalyzes the first step in peroxisomal fatty acid b-oxidation pathway and a target of nuclear transcription factor PPARa [25].…”

Section: Discussionmentioning

confidence: 99%

“…Our gene expression measurements suggest that the retroconversion activity is mediated by both mitochondrial and peroxisomal β-oxidation systems in a cell type dependent manner. Highly expressed in MCF7 cells are (a) mitochondrial Carnitine palmitoyl transferase I (CPT1), coding for the enzyme which shuttles long-chain fatty acids into the mitochondria (Pucci, et al 2016), ECI1 catalyzing the migration of the double bond of both cis and trans-3-enoyl-CoA esters to trans-2-enoyl-CoA (Novikov, et al 1999;van Weeghel, et al 2012) and DECR1 which reduces conjugated Δ2,Δ4-dienoyl-CoAs to a Δ3-enoyl-CoA in an NADPH-dependent reaction. Basal CPT1A mRNA are significantly higher in MCF7 cells compared to normal breast epithelial cell line 184B5 (Linher-Melville, et al 2011).…”

Section: Discussionmentioning

confidence: 99%

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Metabolic fate of docosahexaenoic acid (DHA; 22:6n‐3) in human cells: direct retroconversion of DHA to eicosapentaenoic acid (20:5n‐3) dominates over elongation to tetracosahexaenoic acid (24:6n‐3)

et al. 2016

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Docosahexaenoic acid (22:6n-3) supplementation in humans causes eicosapentaenoic acid (20:5n-3) levels to rise in plasma, but not in neural tissue where 22:6n-3 is the major omega-3 in phospholipids. We determined whether neuronal cells (Y79 and SK-N-SH) metabolize 22:6n-3 differently from non-neuronal cells (MCF7 and HepG2). We observed that 13C-labeled 22:6n-3 was primarily esterified into cell lipids. We also observed that retroconversion of 22:6n-3 to 20:5n-3 was 5- to 6-fold greater in non-neural compared to neural cells and that retroconversion predominated over elongation to tetracosahexaenoic acid (24:6n-3) by 2- to 5-fold. The putative metabolic intermediates, 13C-labeled 22:5n-3 and 13C-labeled 24:5n-3, were not detected in our assays. Analysis of the expression of enzymes involved in fatty acid beta-oxidation revealed that MCF7 cells abundantly expressed the mitochondrial enzymes CPT1A, ECI1, and DECR1, whereas the peroxisomal enzyme ACOX1 was abundant in HepG2 cells, thus suggesting that the initial site of 22:6n-3 oxidation depends on the cell type. Our data reveal that non-neural cells more actively metabolize 22:6n-3 to 20:5n-3 via channeled retroconversion, while neural cells retain 22:6n-3.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metabolic fate of docosahexaenoic acid (DHA; 22:6n‐3) in human cells: direct retroconversion of DHA to eicosapentaenoic acid (20:5n‐3) dominates over elongation to tetracosahexaenoic acid (24:6n‐3)

et al. 2016

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“…5). By combining the action of auxiliary enzymes with those of the main β‐oxidation pathway, metabolism of (poly)unsaturated enoyl‐CoA esters can proceed, at least in principle, via alternative routes [130].…”

Section: Classical and Auxiliary Enzymes Of Peroxisomal β‐Oxidationmentioning

confidence: 99%

The biochemistry of peroxisomal β-oxidation in the yeastSaccharomyces cerevisiae

Hiltunen¹,

Mursula²,

et al. 2003

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Peroxisomal fatty acid degradation in the yeast Saccharomyces cerevisiae requires an array of beta-oxidation enzyme activities as well as a set of auxiliary activities to provide the beta-oxidation machinery with the proper substrates. The corresponding classical and auxiliary enzymes of beta-oxidation have been completely characterized, many at the structural level with the identification of catalytic residues. Import of fatty acids from the growth medium involves passive diffusion in combination with an active, protein-mediated component that includes acyl-CoA ligases, illustrating the intimate linkage between fatty acid import and activation. The main factors involved in protein import into peroxisomes are also known, but only one peroxisomal metabolite transporter has been characterized in detail, Ant1p, which exchanges intraperoxisomal AMP with cytosolic ATP. The other known transporter is Pxa1p-Pxa2p, which bears similarity to the human adrenoleukodystrophy protein ALDP. The major players in the regulation of fatty acid-induced gene expression are Pip2p and Oaf1p, which unite to form a transcription factor that binds to oleate response elements in the promoter regions of genes encoding peroxisomal proteins. Adr1p, a transcription factor, binding upstream activating sequence 1, also regulates key genes involved in beta-oxidation. The development of new, postgenomic-era tools allows for the characterization of the entire transcriptome involved in beta-oxidation and will facilitate the identification of novel proteins as well as the characterization of protein families involved in this process.

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“…Sprecher (26) has postulated the hypothesis that the ␤-oxidation of C22:6n-3 is a relatively slow process, because auxiliary enzymes are required. First, an NADPH-dependent 2,4-dienoyl-CoA reductase has to reduce 2-trans-4-cis-7,10,13,16,19-C22:7(n-3)-CoA to a 3-trans-enoylCoA, which has to be converted into a 2-trans-enoyl-CoA by the ⌬ 3 ,⌬ 2 -enoyl-CoA isomerase, after which it can reenter the ␤-oxidation spiral (27). In contrast, for ␤-oxidation of C24:6n-3, only the enzymes of the ␤-oxidation system are required.…”

Section: Discussionmentioning

confidence: 99%

Studies on the metabolic fate of n-3 polyunsaturated fatty acids

Ferdinandusse

Denis

Dacremont

et al. 2003

Journal of Lipid Research

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Several different processes involved in the metabolic fate of docosahexaenoic acid (DHA, C22:6n-3) and its precursor in the biosynthesis route, C24:6n-3, were studied. In cultured skin fibroblasts, the oxidation rate of [1-14 C] 24:6n-3 was 2.7 times higher than for [1-14 C]22:6n-3, whereas [1-14 C]22:6n-3 was incorporated 7 times faster into different lipid classes than was [1-14 C]24:6n-3. When determining the peroxisomal acyl-CoA oxidase activity, similar specific activities for C22:6(n-3)-CoA and C24:6(n-3)-CoA were found in mouse kidney peroxisomes. Thioesterase activity was measured for both substrates in mouse kidney peroxisomes as well as mitochondria, and C22:6(n-3)-CoA was hydrolyzed 1.7 times faster than C24:6(n-3)-CoA. These results imply that the preferred metabolic fate of C24:6(n-3)-CoA, after its synthesis in the endoplasmic reticulum (ER), is to move to the peroxisome, where it is ␤ -oxidized, producing C22:6(n-3)-CoA. This DHA-CoA then preferentially moves back, probably as free fatty acid, to the ER, where it is incorporated into membrane lipids. -Ferdinandusse, S., S. Denis, G. Dacremont, and R. J. A. Wanders. Studies on the metabolic fate of n-3 polyunsaturated fatty acids.

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Enzymology of β-Oxidation of (Poly)unsaturated Fatty Acids

Cited by 6 publications

References 49 publications

Metabolic fate of docosahexaenoic acid (DHA; 22:6n‐3) in human cells: direct retroconversion of DHA to eicosapentaenoic acid (20:5n‐3) dominates over elongation to tetracosahexaenoic acid (24:6n‐3)

Metabolic fate of docosahexaenoic acid (DHA; 22:6n‐3) in human cells: direct retroconversion of DHA to eicosapentaenoic acid (20:5n‐3) dominates over elongation to tetracosahexaenoic acid (24:6n‐3)

The biochemistry of peroxisomal β-oxidation in the yeastSaccharomyces cerevisiae

Studies on the metabolic fate of n-3 polyunsaturated fatty acids

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