Abstract

The common theme of the 3 sections of this proposal is the metabolism of ketone bodies. In the first section, we describe our ongoing research on the potential of R- and S-1, 3-butanediol as parenteral nutrients. We emphasize the interest in S-1, 3- butanediol as a nutrient in diabetes. The metabolism of the 2 enantiomers and of their corresponding 3-hydroxyacids will be studied in perfused organs and in vivo. In the second section, we build on our recent finding that acetone is converted to acetate in the liver. We propose investigations aimed at quantitating the metabolism of acetone via two- and three-carbon pathways. In the third section we propose to investigate the artifact of pseudo-ketogenesis in peripheral tissues. Pseudo-ketogenesis is a process which dilutes the specific activities of plasma acetoacetate and R-3-hydroxy-butyrate, by label exchange via the reversal of the reaction catalyzed by 3-oxoacid-CoA transferase. This artifact leads to overestimations of the rate of ketogenesis measured in vivo by isotope dilution techniques.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035543-04
Application #
3233863
Study Section
Biochemistry Study Section (BIO)
Project Start
1985-04-01
Project End
1990-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Notre Dame Hospital
Department
Type
DUNS #
City
Montreal
State
Country
Canada
Zip Code

  Publications

Roe, Charles R; Brunengraber, Henri (2015) Anaplerotic treatment of long-chain fat oxidation disorders with triheptanoin: Review of 15 years Experience. Mol Genet Metab 116:260-8
Kinman, Renee P; Kasumov, Takhar; Jobbins, Kathryn A et al. (2006) Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. Am J Physiol Endocrinol Metab 291:E860-6
Okere, Isidore C; McElfresh, Tracy A; Brunengraber, Daniel Z et al. (2006) Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion. J Appl Physiol 100:76-82
Bian, Fang; Kasumov, Takhar; Thomas, Katherine R et al. (2005) Peroxisomal and mitochondrial oxidation of fatty acids in the heart, assessed from the 13C labeling of malonyl-CoA and the acetyl moiety of citrate. J Biol Chem 280:9265-71
Kasumov, Takhar; Adams, Jillian E; Bian, Fang et al. (2005) Probing peroxisomal beta-oxidation and the labelling of acetyl-CoA proxies with [1-(13C)]octanoate and [3-(13C)]octanoate in the perfused rat liver. Biochem J 389:397-401
Yu, Lynn; Sinha, Amit K; Previs, Stephen F (2005) Effect of sampling interval on the use of ""doubly labeled"" water for measuring CO2 production. Anal Biochem 337:343-6
Reszko, Aneta E; Kasumov, Takhar; David, France et al. (2004) Peroxisomal fatty acid oxidation is a substantial source of the acetyl moiety of malonyl-CoA in rat heart. J Biol Chem 279:19574-9
Bederman, Ilya R; Kasumov, Takhar; Reszko, Aneta E et al. (2004) In vitro modeling of fatty acid synthesis under conditions simulating the zonation of lipogenic [13C]acetyl-CoA enrichment in the liver. J Biol Chem 279:43217-26
Reszko, Aneta E; Kasumov, Takhar; David, France et al. (2004) Regulation of malonyl-CoA concentration and turnover in the normal heart. J Biol Chem 279:34298-301
Bederman, Ilya R; Reszko, Aneta E; Kasumov, Takhar et al. (2004) Zonation of labeling of lipogenic acetyl-CoA across the liver: implications for studies of lipogenesis by mass isotopomer analysis. J Biol Chem 279:43207-16

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