American Journal of Clinical Nutrition, Vol 23, 972-985, Copyright © 1970 by The American Society for Clinical Nutrition, Inc.

Mechanism of Inhibition of Gluconeogenesis by 4-Pentenoic Acid

¹ From the Departments of Medicine, Physiology, and Pharmacology, Duke University Medical Center, Durham, North Carolina

The depressant effect of 4-pentenoic acid on gluconeogenesis may be due to the following sequences of events: 1) activation of 4-pentenoic acid to an acyl CoA and transacylation to an acylcarnitine (depletion of extramitochondrial coenzyme A and carnitine) and 2) 4-pentenoylcarnitine enters the mitochondria and is reconverted to 4-pentenoyl CoA, which is oxidized to acryloyl CoA. Acryloyl CoA cannot be oxidized readily and depletes free intramitochondrial coenzyme A (and carnitine). Depletion of extra- and intramitochondrial coenzyme A results in inhibition of fatty acid oxidation (initially long-chain, then medium-chain acids). The inhibition of fatty acid oxidation results in deficient generation of acetyl CoA and DPNH needed for gluconeogenesis (Fig. 5).