Biosynthesis of S-methyl-N-oleoylmercaptoethylamide from oleoyl coenzyme A and S-adenosylmethionine.

Zatz, Martin; Engelsen, S.; Markey, Sanford P.

doi:10.1016/s0021-9258(18)33499-9

Cited by 9 publications

(7 citation statements)

References 11 publications

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“…41,42 The exact mechanism of the generation of these lipid species is as yet unknown and requires further investigation. However, two enzymatic pathways/enzymes exist which in theory could produce S-(3-hydroxyacyl)cysteamines, pantheteinase (VNN) 42 and/ or amidase 43,44 activity. Pantheteinase catalyzes the last step of the CoA degradation pathway, but is generally regarded as an extracellular protein 42 making this possibility less likely.…”

Section: Discussionmentioning

confidence: 99%

“…Pantheteinase catalyzes the last step of the CoA degradation pathway, but is generally regarded as an extracellular protein 42 making this possibility less likely. Accumulating 3‐hydroxyacyl‐CoAs could also be processed by an amidase, an enzyme that previously has been described to catalyze the one‐step generation of acylcysteamines from acyl‐CoAs 43,44 …”

Section: Discussionmentioning

confidence: 99%

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Tracer‐based lipidomics enables the discovery of disease‐specific candidate biomarkers in mitochondrial β‐oxidation disorders

Schwantje,

Mosegaard,

Knottnerus

et al. 2024

The FASEB Journal

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Carnitine derivatives of disease‐specific acyl‐CoAs are the diagnostic hallmark for long‐chain fatty acid β‐oxidation disorders (lcFAOD), including carnitine shuttle deficiencies, very‐long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD), long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MPTD). The exact consequence of accumulating lcFAO‐intermediates and their influence on cellular lipid homeostasis is, however, still unknown. To investigate the fate and cellular effects of the accumulating lcFAO‐intermediates and to explore the presence of disease‐specific markers, we used tracer‐based lipidomics with deuterium‐labeled oleic acid (D9‐C18:1) in lcFAOD patient‐derived fibroblasts. In line with previous studies, we observed a trend towards neutral lipid accumulation in lcFAOD. In addition, we detected a direct connection between the chain length and patterns of (un)saturation of accumulating acylcarnitines and the various enzyme deficiencies. Our results also identified two disease‐specific candidate biomarkers. Lysophosphatidylcholine(14:1) (LPC(14:1)) was specifically increased in severe VLCADD compared to mild VLCADD and control samples. This was confirmed in plasma samples showing an inverse correlation with enzyme activity, which was better than the classic diagnostic marker C14:1‐carnitine. The second candidate biomarker was an unknown lipid class, which we identified as S‐(3‐hydroxyacyl)cysteamines. We hypothesized that these were degradation products of the CoA moiety of accumulating 3‐hydroxyacyl‐CoAs. S‐(3‐hydroxyacyl)cysteamines were significantly increased in LCHADD compared to controls and other lcFAOD, including MTPD. Our findings suggest extensive alternative lipid metabolism in lcFAOD and confirm that lcFAOD accumulate neutral lipid species. In addition, we present two disease‐specific candidate biomarkers for VLCADD and LCHADD, that may have significant relevance for disease diagnosis, prognosis, and monitoring.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tracer‐based lipidomics enables the discovery of disease‐specific candidate biomarkers in mitochondrial β‐oxidation disorders

Schwantje,

Mosegaard,

Knottnerus

et al. 2024

The FASEB Journal

View full text Add to dashboard Cite

show abstract

“…Pantheteinase (VNN) catalyzes the last step of the CoA degradation pathway but is generally regarded as an extracellular protein 39 . Accumulating 3-hydroxyacyl-CoAs could also be processed by an amidase, an enzyme that previously has been described to catalyze the once-step process in which acyl-CoAs are formed into acylcysteamines 40,41 .…”

Section: Discussionmentioning

confidence: 99%

“…The exact mechanism of the generation of these lipid species is as yet unknown and requires further investigations. However, two enzymatic pathways/enzymes exist which in theory could produce S-(3-hydroxyacyl)cysteamines, pantheteinase 39 and/or amidase 40,41 activity. Pantheteinase (VNN) catalyzes the last step of the CoA degradation pathway but is generally regarded as an extracellular protein 39 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tracer-based lipidomics identifies novel disease-specific biomarkers in mitochondrial β-oxidation disorders

Schwantje,

Mosegaard,

Knottnerus

et al. 2023

Preprint

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Carnitine derivatives of disease-specific acyl-CoAs are the diagnostic hallmark for long-chain fatty acid oxidation disorders (lcFAOD), including carnitine shuttle deficiencies, very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MPTD). The exact consequence of accumulating lcFAO-intermediates and possible influence on cellular lipid homeostasis are, however, still unknown. To investigate the fate and cellular effects of the accumulating lcFAO-intermediates and to explore new disease markers, we used tracer-based lipidomics with deuterium-labeled oleic acid (D9-C18:1) in lcFAOD patient-derived fibroblasts. In line with previous studies, we observed a trend towards neutral lipid accumulation in lcFAOD. In addition, we detected a direct connection between the chain length and patterns of (un)saturation of accumulating acylcarnitines and the various enzyme deficiencies. Our results also identified two new candidate disease markers. Lysophosphatidylcholine(14:1) (LPC(14:1)) was specifically increased in severe VLCADD compared to mild VLCADD and control samples. This was confirmed in plasma samples showing an inverse correlation with enzyme activity, which was better than the classic diagnostic marker C14:1-carnitine. The second biomarker is an unknown lipid class, which we identified as S-(3-hydroxyacyl)cysteamines. These are hypothesized to be degradation products of the CoA moiety of accumulating 3-hydroxyacyl-CoAs. S-(3-hydroxyacyl)cysteamines were significantly increased in LCHADD compared to controls and other lcFAOD, including MTPD. Our findings suggest extensive alternative lipid metabolism in lcFAOD and confirm that lcFAOD accumulate neutral lipid species. In addition, we present two new disease markers for VLCADD and LCHADD, that may have significant relevance for disease diagnosis, prognosis, and monitoring.

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Peroxisomal Oxidases and Their Probable Role in Controlling Animal Metabolism

Hamilton

Afeefy

Al-Arab

et al. 1987

Proceedings in Life Sciences

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Biosynthesis of S-methyl-N-oleoylmercaptoethylamide from oleoyl coenzyme A and S-adenosylmethionine.

Cited by 9 publications

References 11 publications

Tracer‐based lipidomics enables the discovery of disease‐specific candidate biomarkers in mitochondrial β‐oxidation disorders

Tracer‐based lipidomics enables the discovery of disease‐specific candidate biomarkers in mitochondrial β‐oxidation disorders

Tracer-based lipidomics identifies novel disease-specific biomarkers in mitochondrial β-oxidation disorders

Peroxisomal Oxidases and Their Probable Role in Controlling Animal Metabolism

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