In vivo studies on the mechanism of methylene cyclopropyl acetic acid and methylene cyclopropyl glycine-induced hypoglycemia

The Biochemical Journal
Yang QiuDaniel F Vatner

Abstract

Exposure to the toxins methylene cyclopropyl acetic acid (MCPA) and methylene cyclopropyl glycine (MCPG) of unripe ackee and litchi fruit can lead to hypoglycemia and death; however, the molecular mechanisms by which MCPA and MCPG cause hypoglycemia have not been established in vivo To determine the in vivo mechanisms of action of these toxins, we infused them into conscious rodents and assessed rates of hepatic gluconeogenesis and ketogenesis, hepatic acyl-CoA and hepatic acetyl-CoA content, and hepatocellular energy charge. MCPG suppressed rates of hepatic β-oxidation as reflected by reductions in hepatic ketogenesis, reducing both short- and medium-chain hepatic acyl-CoA concentrations. Hepatic acetyl-CoA content decreased, and hepatic glucose production was inhibited. MCPA also suppressed β-oxidation of short-chain acyl-CoAs, rapidly inhibiting hepatic ketogenesis and hepatic glucose production, depleting hepatic acetyl-CoA content and ATP content, while increasing other short-chain acyl-CoAs. Utilizing a recently developed positional isotopomer NMR tracer analysis method, we demonstrated that MCPA-induced reductions in hepatic acetyl-CoA content were associated with a marked reduction of hepatic pyruvate carboxylase (PC) f...Continue Reading

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Citations

Jun 9, 2020·Transactions of the Royal Society of Tropical Medicine and Hygiene·Abhirup SarkarT Jacob John
Sep 23, 2019·Revue neurologique·V S PalmerP S Spencer
Mar 7, 2021·Journal of Veterinary Internal Medicine·Sonia González-MedinaRichard J Piercy

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