Sander Johannes, Terhardt Michael, Janzen Nils
Screening-Labor Hannover, Hanover, Germany.
Hanover Medical School, Hanover, Germany.
Front Vet Sci. 2021 Oct 26;8:765623. doi: 10.3389/fvets.2021.765623. eCollection 2021.
In horses, congenital defects of energy production from long-chain fatty acids have not been described so far. In contrast, inhibition of fatty acid degradation caused by the toxins hypoglycin A and methylenecyclopropylglycine from various maple species are observed frequently. These non-proteinogenic aminoacids are passed on placentally to fetuses or with collostrum or milk to newborn foals. Nevertheless, newborn foals become very rarely symptomatic. Vertical transmission apparently is not sufficient to induce clinical disease without a particular genetic constellation being present. One of these rare cases was investigated here using samples from a mare and her foal. Intoxication by hypoglycin A and methylenecyclopropylglycine is also of interest to human pathology, because these toxins have caused fatal poisonings after consumption of certain fruits many times, especially in children. Maple toxins, their metabolites and some short-chain acyl compounds were quantified by ultrahigh-pressure liquid chromatography/tandem mass spectrometry. An comprehensive spectrum of long-chain acylcarnitines was prepared using electrospray ionization tandem mass spectrometry. Organic acids and acylglycines were determined by gas chromatography mass spectrometry. For evaluation, results of other horses poisoned by maple material as well as unaffected control animals were used. In the serum of the foal, hypoglycin A was detected at a low concentration only. Toxin metabolites reached <3.5% of the mean of a comparison group of horses suffering from atypical myopathy. The spectrum of acylcarnitines indicated enzyme inhibition in short-chain and medium-chain regions typical of acer poisoning, but the measured concentrations did not exceed those previously found in clinically healthy animals after maple consumption. The values were not sufficient to explain the clinical symptoms. In contrast, a remarkably strong enrichment of tetradecenoylcarnitine and hexadecenoylcarnitine was observed. This proves a blockade of the long-chain enoyl-CoA hydratase (EC 4.2.1.74). Vertical transfer of maple toxins to a newborn foal is sufficient for induction of clinical disease only if there is an additional specific reactivity to the active toxins. This was found here in an inhibition of long-chain enoyl-CoA hydratase. Isolated dysfunction of this enzyme has not yet been reported in any species. Further studies are necessary to prove a specific genetic defect.
迄今为止，尚未发现马存在长链脂肪酸能量生成的先天性缺陷。相反，经常观察到各种枫树中的毒素降血糖素A和亚甲基环丙基甘氨酸会抑制脂肪酸降解。这些非蛋白质氨基酸可通过胎盘传递给胎儿，或通过初乳或乳汁传递给新生马驹。然而，新生马驹很少出现症状。显然，垂直传播在没有特定基因组合的情况下不足以引发临床疾病。本文利用一匹母马及其马驹的样本对其中一个罕见病例进行了研究。降血糖素A和亚甲基环丙基甘氨酸中毒对人类病理学也很重要，因为这些毒素多次导致食用某些水果后发生致命中毒，尤其是在儿童中。通过超高压液相色谱/串联质谱法定量分析了枫树毒素、其代谢产物和一些短链酰基化合物。使用电喷雾电离串联质谱法制备了长链酰基肉碱的综合谱图。通过气相色谱质谱法测定有机酸和酰基甘氨酸。为了进行评估，使用了其他因枫树物质中毒的马以及未受影响的对照动物的结果。在马驹的血清中，仅检测到低浓度的降血糖素A。毒素代谢产物占非典型肌病马比较组平均值的比例不到3.5%。酰基肉碱谱图表明在枫树中毒典型的短链和中链区域存在酶抑制，但测得的浓度未超过先前在食用枫树后临床健康动物中发现的浓度。这些值不足以解释临床症状。相反，观察到十四碳烯酰肉碱和十六碳烯酰肉碱显著强烈富集。这证明了长链烯酰辅酶A水合酶（EC 4.2.1.74）的阻断。只有当对活性毒素存在额外的特异性反应时，枫树毒素向新生马驹的垂直转移才足以引发临床疾病。本文在此发现了长链烯酰辅酶A水合酶的抑制作用。尚未在任何物种中报道过该酶的孤立功能障碍。需要进一步研究以证明特定的基因缺陷。
