Abstract

The long-term goal of the investigations for which a continuation of support is sought are: (i) To develop new nutrienti for parenteral and enteral nutrition, and for nutritional treatment of diabetes. (ii) to improve our understanding of alterations of ketone body metabolism occurring in diabetes. During the next five years, we wish to achieve four specific aims: 1. To study the metabolism of the R- and S- isomers of 1,3-butanediol and 1,3-pentanediol in perfused rat organs, in live rats, dogs and monkeys. 2. To validate the non-invasive chemical biopsy of human liver, under minimal or zero load of xenobiotic. This technique will then be used: 3. To quantitate pseudoketogenesis in extrahepatic tissues, and to develop non-invasive methods for assessing the net metabolic load of ketone bodies. 4. To assess (i) the distribution of acetone metabolism between two-carbon and three-carbon pathways, and (ii) the origin of plasma acetate.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035543-08
Application #
3233866
Study Section
Metabolism Study Section (MET)
Project Start
1985-04-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  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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