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Interrelations between C 4 ‐ketogenesis and C 5 ‐ketogenesis in the perfused rat liver
Author(s) -
DENG Shuang,
Zhang Guofang,
Kasumov Takhar,
David France,
Roe Charles R.,
Brunengraber Henri
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.680.1
Subject(s) - ketogenesis , propionate , ketone bodies , gluconeogenesis , chemistry , ketone , moiety , beta oxidation , fatty acid , glycerol , biochemistry , metabolism , stereochemistry , organic chemistry
C 5 ‐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). C 5 ‐ketogenesis results in the transfer of part of the anaplerotic propionyl moiety of triheptanoin to peripheral tissues. We investigated interrelations between C 4 ‐ and C 5 ‐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 C 5 ‐ketone bodies from heptanoate was lower than that of C 4 ‐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 C 4 ‐ketogenesis over C 5 ‐ketogenesis. C 4 ‐ketogenesis and C 5 ‐ketogenesis share the same acetyl‐CoA pool. Very little propionate is converted to C 5 ‐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 C 5 ‐ketone body formation requires an odd‐chain fatty acid with at least 5 C. Supported by NIH.