Interrelations between C4 ketogenesis, C5 ketogenesis, and anaplerosis in the perfused rat liver.

Published

Journal Article

We investigated the interrelations between C(4) ketogenesis (production of beta-hydroxybutyrate + acetoacetate), C(5) ketogenesis (production of beta-hydroxypentanoate + beta-ketopentanoate), and anaplerosis in isolated rat livers perfused with (13)C-labeled octanoate, heptanoate, or propionate. Mass isotopomer analysis of C(4) and C(5) ketone bodies and of related acyl-CoA esters reveal that C(4) and C(5) ketogenesis share the same pool of acetyl-CoA. Although the uptake of octanoate and heptanoate by the liver are similar, the rate of C(5) ketogenesis from heptanoate is much lower than the rate of C(4) ketogenesis from octanoate. This results from the channeling of the propionyl moiety of heptanoate into anaplerosis of the citric acid cycle. C(5) ketogenesis from propionate is virtually nil because acetoacyl-CoA thiolase does not favor the formation of beta-ketopentanoyl-CoA from propionyl-CoA and acetyl-CoA. Anaplerosis and gluconeogenesis from heptanoate are inhibited by octanoate. The data have implications for the design of diets for the treatment of long chain fatty acid oxidation disorders, such as the triheptanoin-based diet.

Full Text

Duke Authors

Cited Authors

  • Deng, S; Zhang, G-F; Kasumov, T; Roe, CR; Brunengraber, H

Published Date

  • October 9, 2009

Published In

Volume / Issue

  • 284 / 41

Start / End Page

  • 27799 - 27807

PubMed ID

  • 19666922

Pubmed Central ID

  • 19666922

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M109.048744

Language

  • eng

Conference Location

  • United States