Detection of MCPG metabolites in horses with atypical myopathy

被引：25

作者：

Bochnia, Mandy ^{[1
]}

Sander, Johannes ^{[2
]}

Ziegler, Joerg ^{[3
]}

Terhardt, Michael ^{[2
]}

Sander, Stefanie ^{[2
]}

Janzen, Nils ^{[2
,4
]}

Cavalleri, Jessika-M. V. ^{[5
]}

Zuraw, Aleksandra ^{[6
]}

Wensch-Dorendorf, Monika ^{[7
]}

Zeyner, Annette ^{[1
]}

机构：

[1] Martin Luther Univ Halle Wittenberg, Inst Agr & Nutr Sci, Grp Anim Nutr, Halle, Saale, Germany

[2] Screening Labor Hannover, Hannover, Germany

[3] Leibniz Inst Plant Biochem, Dept Mol Signal Proc, Halle, Saale, Germany

[4] Hannover Med Sch, Dept Clin Chem, Hannover, Germany

[5] Univ Vet Med Hannover, Clin Horses, Hannover, Germany

[6] Definiens AG, Munich, Germany

[7] Martin Luther Univ Halle Wittenberg, Inst Agr & Nutr Sci, Grp Biometr, Halle, Saale, Germany

来源：

PLOS ONE | 2019年 / 14卷 / 02期

关键词：

ACKEE BLIGHIA-SAPIDA; COA DEHYDROGENASE-DEFICIENCY; JAMAICAN VOMITING SICKNESS; HYPOGLYCIN-A; ACUTE ENCEPHALITIS; QUANTIFICATION; IDENTIFICATION; INGESTION; MECHANISM; CHILDREN;

D O I：

10.1371/journal.pone.0211698

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 beta-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 chro-matography-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 beta-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 beta-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.

引用

页数：18

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