Metabolic consequences of methylenecyclopropylglycine poisoning in rats

Abstract

We describe the effects of methylenecyclopropylglycine in fasted rats. A 75% decrease in the blood glucose concentration and an increase of lactate and pyruvate were observed 6 h after administration of 100 mg of this amino acid/kg. By contrast with the effects reported for hypoglycin [Williamson & Wilson (1965) Biochem. J. 94, 19c-21c], the plasma concentrations of ketone bodies decreased after administration of methylenecyclopropylglycine and the concentrations of branched-chain amino acids in the plasma were increased 6-fold. The oxidation of decanoylcarnitine or of palmitate was nearly completely inhibited in rat liver mitochondria from methylenecyclopropylglycine-poisoned rats. The activities of acetoacetyl-CoA and of 3-oxoacyl-CoA thiolase were decreased to 25% and less than 10% of the controls. There was a pronounced aciduria, due to the excretion of dicarboxylic acids and of oxidation products of branched-chain amino acids. The accumulation of the toxic metabolite methylenecyclopropylformyl-CoA in the mitochondrial matrix was detected after administration of methylenecyclopropylglycine. Similarly we confirmed experimentally that methylenecyclopropylacetyl-CoA accumulates in mitochondria incubated with methylenecyclopropylpyruvate.

Evidence for the Natural Toxins from the Mushroom Trogia venenata as a Cause of Sudden Unexpected Death in Yunnan Province, China

“…Consequently, cells can no longer use lipids as an energy source, and a profound hypoglycemia results. [16,17] In the chemical structures of 1 and 2 there is a d-unsaturated bond, which is similar to hypoglycin. Further investigations are needed to determine if 1 and 2 have this specific or a similar biochemical effect.…”

Quantification of Metabolites for Assessing Human Exposure to Soapberry Toxins Hypoglycin A and Methylenecyclopropylglycine

“…Hypoglycin A has been isolated from the seeds of longan fruit while both hypoglycin A and methylenecyclopropylglycine (MCPG) have been recovered from lychee seeds. 20–22 Similar to hypoglycin A, MCPG is metabolized to a toxic CoA ester (Scheme 1), methylenecyclopropylformyl-CoA (MCPF-CoA). 22–28 MCPG has been implicated as a potential cause of AES, 27–29 an ongoing public health problem in Asia, 30–32 which bears a clinical resemblance to Reye’s syndrome 33 .…”

“…34–35 Both hypoglycin A and MCPG are documented compounds that can induce encephalopathy and hypoglycemia in animal studies. 8–12,22,26 …”

“…14 Previous studies suggest that MCPG undergoes a similar metabolic pathway to that of hypoglycin A. 22–28 In the case of MCPG, α-oxidation forms MCP-glyoxalate, which is decarboxylated and conjugated as a CoA ester (MCPF-CoA). MCPF-CoA is also reported to inhibit α–oxidation of fatty acids but at a different stage than MCPA-CoA.…”

“…The metabolism of hypoglycin A and MCPG, as compiled from previous literature, is provided in Scheme 1. 3,6,8–14,22–27 …”