Interrelations between C4‐ketogenesis and C5‐ketogenesis in the perfused rat liver

Abstract

C5‐Ketone bodies, 3‐hydroxypentanoate and 3‐ketopentanoate, are products of odd‐chain fatty acid oxidation in liver. They are formed when patients with long‐chain fatty acid oxidation disorders are treated with anaplerotic triheptanoin (glycerol‐triheptanoate; Roe et al J. Clin. Invest. 110: 259, 2002). C5‐ketogenesis results in the transfer of part of the anaplerotic propionyl moiety of triheptanoin to peripheral tissues. We investigated interrelations between C4‐ and C5‐ketogenesis in rat livers perfused with heptanoate ± octanoate or octanoate ± heptanoate or propionate with different labeling patterns. While uptakes of octanoate and heptanoate were similar, the yield of C5‐ketone bodies from heptanoate was lower than that of C4‐ketone bodies from octanoate. This results from the diversion of propionyl‐CoA moiety of heptanoate to anaplerosis and gluconeogenesis. The competition between octanoate and heptanoate uptakes favors octanoate uptake over heptanoate uptake and C4‐ketogenesis over C5‐ketogenesis. C4‐ketogenesis and C5‐ketogenesis share the same acetyl‐CoA pool. Very little propionate is converted to C5‐ketone bodies because the kinetic properties of 3‐ketoacyl‐CoA thiolase do not allow the formation of 3‐ketopentanoyl‐CoA from propionyl‐CoA + acetyl‐CoA. Thus C5‐ketone body formation requires an odd‐chain fatty acid with at least 5 C. Supported by NIH.