Measurement of free carnitine and acylcarnitines in plasma by HILIC-ESI-MS/MS without derivatization

Peng, Minzhi; Liu, Li; Jiang, Mao Fa; Liang, Cuili; Zhao, Xiaoyuan; Cai, Yamei; Sheng, Huiying; Ou, Zhiying; Hong, Luo

doi:10.1016/j.jchromb.2013.05.028

Cited by 40 publications

(35 citation statements)

References 29 publications

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“…[12][13][14][15] The positive correlation of long-chain acylcarnitines between serum levels and levels in myocardial cells, 11 and the increase of the long-chain acylcarnitines in acute ischemic myocardium (.10 times), 16 suggest an increase of long-chain acylcarnitines in ischemic conditions or other metabolic states. The increase of long-chain acylcarnitines after heart transplantation may be an example of this case (eg, .5 mM of total long-chain acylcarnitines).…”

Section: Discussionmentioning

confidence: 99%

Acylcarnitines are anticoagulants that inhibit factor Xa and are reduced in venous thrombosis, based on metabolomics data

Deguchi¹,

Banerjee²,

Trauger

et al. 2015

Blood

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• Untargeted and targeted metabolomics showed association of low plasma acylcarnitines levels with venous thrombosis risk.• Long-chain acylcarnitines are anticoagulants that inhibit factor Xa by binding to factor Xa outside the g-carboxy glutamic acid domain.In many patients with deep vein thrombosis and pulmonary embolism (venous thromboembolism, VTE), biomarkers or genetic risk factors have not been identified. To discover novel plasma metabolites associated with VTE risk, we employed liquid chromatography-mass spectrometry-based untargeted metabolomics, which do not target any specific metabolites. Using the Scripps Venous Thrombosis Registry population for a case-control study, we discovered that 10:1 and 16:1 acylcarnitines were low in plasmas of the VTE patient group compared with matched controls, respectively. Data from targeted metabolomics studies showed that several long-chain acylcarnitines (10:1, 12:0, 12:2, 18:1, and 18:2) were lower in the VTE group. Clotting assays were used to evaluate a causal relationship for low acylcarnitines in patients with VTE. Various acylcarnitines inhibited factor Xa-initiated clotting. Inhibition of factor Xa by acylcarnitines was greater for longer acyl chains. Mechanistic studies showed that 16:0 acylcarnitine had anticoagulant activity in the absence of factor Va or phospholipids. Surface plasmon resonance investigations revealed that 16:0 acylcarnitine was bound to factor Xa and that binding did not require the g-carboxy glutamic acid domain. In summary, our study identified low plasma levels of acylcarnitines in patients with VTE and showed that acylcarnitines have anticoagulant activity related to an ability to bind and inhibit factor Xa. (Blood. 2015;126(13):1595-1600

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Section: Discussionmentioning

confidence: 99%

Acylcarnitines are anticoagulants that inhibit factor Xa and are reduced in venous thrombosis, based on metabolomics data

Deguchi¹,

Banerjee²,

Trauger

et al. 2015

Blood

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“…Total long‐chain ACs (acyl chains >10 carbons) circulate in plasma, with reported concentrations ranging between 1 and 4 μmol/L, and their levels can reach to 10‐30 μmol/L under certain metabolic conditions . Long‐chain ACs are lipid metabolites with a hydrophobic side chain and a free amine like sphingosine (Figure ), but they belong to the long‐chain AC family which plays an important role in energy metabolism through mitochondrial β‐oxidation of fatty acids .…”

Section: Plasma Phospholipid Derivatives Blood Coagulation and Vtementioning

confidence: 95%

“…Total long-chain ACs (acyl chains >10 carbons) circulate in plasma, with reported concentrations ranging between 1 and 4 μmol/L, 33,[80][81][82] and their levels can reach to 10-30 μmol/L under certain metabolic conditions. [83][84][85][86] Long-chain ACs are lipid metabolites with a hydrophobic side chain and a free amine like sphingosine (Figure 4), but they belong to the long-chain AC family which plays an important role in energy metabolism through mitochondrial β-oxidation of fatty acids. 87 The acylcarnitines and Co-A are produced by the reaction in which acyl moieties are transferred to carnitine from acyl-CoA by carnitine palmitoyl transferase-I (Figure 3, Figure S1, Table S2).…”

Section: Ac Metabolismmentioning

confidence: 99%

Minor plasma lipids modulate clotting factor activities and may affect thrombosis risk

Deguchi

Elias

Griffin

2017

Research and Practice in Thrombosis and Haemostasis

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Summary Different minor abundance plasma lipids significantly influence thrombin generation in vitro and significant differences in such lipids are linked to risk for venous thrombosis. Some plasma sphingolipids including glucosylceramide, lyso-sulfatide and sphingosine have anticoagulant properties whereas, conversely, some plasma phospholipid derivatives, including certain lyso-phospholipids and ethanolamides, have procoagulant properties. Plasma metabolite profiling of venous thrombosis patients showed association of venous thrombosis with decreased plasma long-chain acylcarntines, leading to discovery of their anticoagulant activity as inhibitors of factor Xa. Inhibition of factor Xa by acylcarnitines does not require the protein’s Gla-domain, emphasizing an expanded framework for the paradigm for lipid-clotting factor interactions. Overall, whether by genetics or environment, alterations in the dynamics of lipid metabolism linked to an altered lipidome may contribute to regulation of blood coagulation because imbalances between physiologic procoagulant and anticoagulant lipids may contribute to excessive thrombin generation that augments risk for thrombosis.

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“…Plasma ACs were quantified using the method proposed by Peng et al. . Briefly, protein precipitation was carried out adding 200 μL of MeCN to 50 μL of plasma and 10 μL of internal standards.…”

Section: Methodsmentioning

confidence: 99%

A discovery‐driven approach to elucidate urinary metabolome changes after a regular and moderate consumption of beer and nonalcoholic beer in subjects at high cardiovascular risk

Quifer-Rada

Chiva‐Blanch

Jáuregui

et al. 2017

Molecular Nutrition Food Res

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Measurement of free carnitine and acylcarnitines in plasma by HILIC-ESI-MS/MS without derivatization

Cited by 40 publications

References 29 publications

Acylcarnitines are anticoagulants that inhibit factor Xa and are reduced in venous thrombosis, based on metabolomics data

Acylcarnitines are anticoagulants that inhibit factor Xa and are reduced in venous thrombosis, based on metabolomics data

Minor plasma lipids modulate clotting factor activities and may affect thrombosis risk

A discovery‐driven approach to elucidate urinary metabolome changes after a regular and moderate consumption of beer and nonalcoholic beer in subjects at high cardiovascular risk

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