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PloS one2019; 14(2); e0211698; doi: 10.1371/journal.pone.0211698

Detection of MCPG metabolites in horses with atypical myopathy.

Abstract: Atypical myopathy (AM) in horses is caused by ingestion of seeds of the Acer species (Sapindaceae family). Methylenecyclopropylacetyl-CoA (MCPA-CoA), derived from hypoglycin A (HGA), is currently the only active toxin in Acer pseudoplatanus or Acer negundo seeds related to AM outbreaks. However, seeds or arils of various Sapindaceae (e.g., ackee, lychee, mamoncillo, longan fruit) also contain methylenecyclopropylglycine (MCPG), which is a structural analogue of HGA that can cause hypoglycaemic encephalopathy in humans. The active poison formed from MCPG is methylenecyclopropylformyl-CoA (MCPF-CoA). MCPF-CoA and MCPA-CoA strongly inhibit enzymes that participate in β-oxidation and energy production from fat. The aim of our study was to investigate if MCPG is involved in Acer seed poisoning in horses. MCPG, as well as glycine and carnitine conjugates (MCPF-glycine, MCPF-carnitine), were quantified using high-performance liquid chromatography-tandem mass spectrometry of serum and urine from horses that had ingested Acer pseudoplatanus seeds and developed typical AM symptoms. The results were compared to those of healthy control horses. For comparison, HGA and its glycine and carnitine derivatives were also measured. Additionally, to assess the degree of enzyme inhibition of β-oxidation, several acyl glycines and acyl carnitines were included in the analysis. In addition to HGA and the specific toxic metabolites (MCPA-carnitine and MCPA-glycine), MCPG, MCPF-glycine and MCPF-carnitine were detected in the serum and urine of affected horses. Strong inhibition of β-oxidation was demonstrated by elevated concentrations of all acyl glycines and carnitines, but the highest correlations were observed between MCPF-carnitine and isobutyryl-carnitine (r = 0.93) as well as between MCPA- (and MCPF-) glycine and valeryl-glycine with r = 0.96 (and r = 0.87). As shown here, for biochemical analysis of atypical myopathy of horses, it is necessary to take MCPG and the corresponding metabolites into consideration.
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Publication Date: 2019-02-05 PubMed ID: 30721263PubMed Central: PMC6363182DOI: 10.1371/journal.pone.0211698Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper explains that ingestion of certain seeds from the Acer species can contribute to Atypical Myopathy (AM) in horses, leading to the study’s investigation on the role of methylenecyclopropylglycine (MCPG) in Acer seed poisoning in horses.

Context and Objective of the Study

  • Atypical Myopathy (AM) is a harmful condition in horses caused by the ingestion of seeds from the Acer species (part of the Sapindaceae family).
  • The active toxin in Acer pseudoplatanus or Acer negundo seeds associated with AM is Methylenecyclopropylacetyl-CoA (MCPA-CoA), derived from hypoglycin A (HGA).
  • However, various Sapindaceae seeds also contain MCPG, a structural analogue of HGA, known to cause hypoglycaemic encephalopathy in humans. The toxin formed from MCPG is methylenecyclopropylformyl-CoA (MCPF-CoA).
  • Both MCPF-CoA and MCPA-CoA are known to inhibit enzymes involved in the β-oxidation process and energy production from fat.
  • The study’s objective was to investigate the role of MCPG in Acer seed poisoning in horses.

Methodology and Results

  • To assess MCPG involvement, levels of MCPG and its derivatives (MCPF-glycine, MCPF-carnitine) were measured in the serum and urine of horses that had consumed Acer pseudoplatanus seeds and subsequently exhibited AM symptoms.
  • These readings were contrasted against the results from healthy control horses.
  • Additionally, levels of HGA and its derivatives were also measured simultaneously. Acyl glycines and acyl carnitines were included in analysis to determine how much β-oxidation enzyme activity was inhibited.
  • In addition to HGA and specific toxic metabolites, MCPG along with MCPF-glycine and MCPF-carnitine were detected in the serum and urine of the affected horses.
  • Significant inhibition of β-oxidation was indicated by heightened concentrations of all acyl glycines and carnitines. The highest correlations were found between MCPF-carnitine and isobutyryl-carnitine, and between MCPA-glycine (and MCPF-glycine) and valeryl-glycine.

Conclusion of the Study

  • The study provides evidence suggesting MCPG and its related metabolites play a role in atypical myopathy in horses.
  • For a comprehensive biochemical analysis of atypical myopathy in horses, it is necessary to account for MCPG and its corresponding metabolites.

Cite This Article

APA
Bochnia M, Sander J, Ziegler J, Terhardt M, Sander S, Janzen N, Cavalleri JV, Zuraw A, Wensch-Dorendorf M, Zeyner A. (2019). Detection of MCPG metabolites in horses with atypical myopathy. PLoS One, 14(2), e0211698. https://doi.org/10.1371/journal.pone.0211698

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 14
Issue: 2
Pages: e0211698

Researcher Affiliations

Bochnia, Mandy
  • Group Animal Nutrition, Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Sander, Johannes
  • Screening-Labor Hannover, Hannover, Germany.
Ziegler, Joerg
  • Department of Molecular Signal Processing, Leibniz Institute of Plant Biochemistry, Halle (Saale), Germany.
Terhardt, Michael
  • Screening-Labor Hannover, Hannover, Germany.
Sander, Stefanie
  • Screening-Labor Hannover, Hannover, Germany.
Janzen, Nils
  • Screening-Labor Hannover, Hannover, Germany.
  • Department of Clinical Chemistry, Hanover Medical School, Hannover, Germany.
Cavalleri, Jessika-M V
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Zuraw, Aleksandra
  • Definiens AG, München, Germany.
Wensch-Dorendorf, Monika
  • Group Biometrics, Institute of Agricultural and nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Zeyner, Annette
  • Group Animal Nutrition, Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

MeSH Terms

  • Acer / adverse effects
  • Animals
  • Chromatography, High Pressure Liquid
  • Cyclopropanes / blood
  • Cyclopropanes / metabolism
  • Cyclopropanes / urine
  • Female
  • Glycine / analogs & derivatives
  • Glycine / blood
  • Glycine / metabolism
  • Glycine / urine
  • Horse Diseases / blood
  • Horse Diseases / etiology
  • Horse Diseases / metabolism
  • Horse Diseases / urine
  • Horses / blood
  • Horses / urine
  • Male
  • Metabolic Networks and Pathways
  • Muscular Diseases / etiology
  • Muscular Diseases / metabolism
  • Muscular Diseases / veterinary
  • Plant Poisoning / etiology
  • Plant Poisoning / metabolism
  • Plant Poisoning / veterinary
  • Seeds / adverse effects
  • Tandem Mass Spectrometry

Conflict of Interest Statement

After the present study was completed, Aleksandra Zuraw became employed by Definiens AG. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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Citations

This article has been cited 15 times.
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