Interrelations between C4 ketogenesis, C5 ketogenesis, and anaplerosis in the perfused rat liver.
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.
Deng
Shuang
S
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106.
Zhang
Guo-Fang
GF
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106.
Kasumov
Takhar
T
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106.
Roe
Charles R
CR
Institute of Metabolic Disease, Baylor University Medical Center, Dallas, Texas 75226.
Brunengraber
Henri
H
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106. Electronic address: hxb8@case.edu.
D020155:3-Hydroxybutyric Acid / Q000737:chemistry / Q000378:metabolism*; D000090:Acetoacetates / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002210:Caprylates / Q000737:chemistry / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism; D006537:Heptanoates / Q000737:chemistry / Q000378:metabolism; D007657:Ketone Bodies / Q000096:biosynthesis* / Q000737:chemistry; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010421:Pentanoic Acids / Q000737:chemistry / Q000378:metabolism*; D011422:Propionates / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000090:Acetoacetates; D002210:Caprylates; D005227:Fatty Acids; D006537:Heptanoates; D007657:Ketone Bodies; D010421:Pentanoic Acids; D011422:Propionates; D005947:Glucose; D020155:3-Hydroxybutyric Acid