Authors: Sander Johannes, Terhardt Michael, Janzen Nils, Renaud Benoît, Kruse Caroline-Julia, François Anne-Christine, Wouters Clovis P, Boemer François, Votion Dominique-Marie
Journal: Animals : an open access journal from MDPI
Summary
# Editorial Summary Equine atypical myopathy (AM) results from ingestion of sycamore maple seeds containing two protoxins—hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG)—but their precise metabolic pathways and tissue distribution remain poorly characterised. Johannes and colleagues analysed tissue samples from five AM cases to map how these protoxins are activated and metabolised, focusing particularly on where toxin conversion occurs and which tissues accumulate toxic metabolites. Their findings revealed that whilst HGA was detected unmetabolised in organs, both protoxins underwent activation primarily in skeletal muscle tissue, generating MCPA-CoA and MCPF-CoA intermediates that subsequently inhibited multiple acyl-CoA dehydrogenases involved in fatty acid oxidation; this enzyme inhibition caused pronounced accumulation of short-, medium- and branched-chain acylcarnitines predominantly in muscle, whilst long-chain acylcarnitines did not accumulate abnormally. The authors propose that interrupting protoxin metabolisation—specifically by inhibiting the mitochondrial branched-chain amino acid aminotransferase enzyme responsible for initiating sycamore maple toxin activation—may represent a novel therapeutic strategy to halt disease progression. For equine professionals managing AM cases, these findings suggest that interventions targeting early metabolic activation steps could be more effective than attempting to eliminate toxin after systemic distribution, potentially opening new treatment pathways beyond current supportive care.
Read the full abstract on PubMed
Practical Takeaways
- •Blocking the mitochondrial branched-chain amino acid aminotransferase enzyme represents a potential therapeutic approach to prevent atypical myopathy progression in sycamore maple exposure cases
- •Skeletal muscle is the primary site of toxin activation and accumulation in atypical myopathy, highlighting why clinical signs present as myopathy rather than systemic toxemia
- •Further research into metabolic inhibitors may offer preventive or treatment options for horses at risk of sycamore maple poisoning
Key Findings
- •Only hypoglycin A was detected in tissues from five atypical myopathy cases; methylenecyclopropylglycine presence was not confirmed
- •Activation of protoxins to toxic acyl-CoA derivatives occurred predominantly in skeletal muscle tissue with very high concentrations of MCPA-carnitine and MCPF-carnitine detected
- •Toxins inhibited short-, medium-, and branched-chain fatty acid acyl-CoA dehydrogenases, causing marked accumulation of corresponding acylcarnitines preferentially in skeletal muscle
- •High amounts of unmetabolized hypoglycin A were consistently found in organs, suggesting interruption of metabolization could be a therapeutic target