The autocoids derived from different unsaturated fatty acids mediate physiological processes in diverse ways. The types and amounts of autocoids produced in any cell depend on what unsaturated fatty acids are found in individual phospholipids for agonist induced release by specific lipases for subsequent metabolism to leukotrienes and prostaglandins. Phospholipid unsaturated fatty acid composition differs between prostaglandin producing cells.
Aim one of this study involves carefully controlled rat feeding studies using deuterated unsaturated acids, to define what differences exist in their time dependent incorporation into individual phospholipids in a number of prostaglandin producing tissues. These feeding studies will also define whether unsaturated fatty acid and phospholipid biosynthesis are coupled metabolic processes and what differences exist in the tissues which make their own polyunsaturated acids versus granulocytes and platelets which largely depend on plasma for acids for phospholipid synthesis. Competitive feeding studies with deuterated (n-3) and (n-6) acids will compare how these acids are metabolized and incorporated into specific phospholipids and what differences exist between lipids within a tissue and between tissues. In the second phase of these studies rat hepatocytes will be incubated with various radioactive (n-6) and (n-3) polyunsaturated fatty acids to define 1. What differences exist between (n-3) and (n-6) fatty acid metabolism and their incorporation into specific lipids. 2. Whether the lipogenic state of the liver, as influenced by dietary fat change, modifies the way (n-6) and (n-3) acids are metabolized and incorporated into both liver lipids and triglycerides secreted into the medium. 3. What competitive interactions exist between arachidonic acid and long chain (n-3) acids for acylation. The third phase of these studies will define what regulates the synthesis of 22-carbon (n-3) and (n-6) fatty acids with particular emphasis on elucidating the pathway by which a double bond is introduced at position-4 of unsaturated acids. The overall goal of these studies is to determine how dietary fat change regulates the unsaturated fatty acid composition of individual phospholipids in prostaglandin producing tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK018844-13
Application #
3226154
Study Section
Nutrition Study Section (NTN)
Project Start
1976-05-01
Project End
1991-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
13
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Voss, A; Reinhart, M; Sprecher, H (1992) Differences in the interconversion between 20- and 22-carbon (n - 3) and (n - 6) polyunsaturated fatty acids in rat liver. Biochim Biophys Acta 1127:33-40
Hadjiagapiou, C; Travers, J; Fertel, R et al. (1992) Beta-oxidation of 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid by MOLT-4 lymphocytes. Arch Biochem Biophys 292:112-20
Sprecher, H (1991) Enzyme activities affecting tissue lipid fatty acid composition. World Rev Nutr Diet 66:166-76
Voss, A; Reinhart, M; Sankarappa, S et al. (1991) The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturase. J Biol Chem 266:19995-20000
MacDonald, J I; Sprecher, H (1991) Phospholipid fatty acid remodeling in mammalian cells. Biochim Biophys Acta 1084:105-21
Rosenthal, M D; Garcia, M C; Jones, M R et al. (1991) Retroconversion and delta 4 desaturation of docosatetraenoate (22:4(n-6)) and docosapentaenoate (22:5(n-3)) by human cells in culture. Biochim Biophys Acta 1083:29-36
Kuhn, H; Sprecher, H; Brash, A R (1990) On singular or dual positional specificity of lipoxygenases. The number of chiral products varies with alignment of methylene groups at the active site of the enzyme. J Biol Chem 265:16300-5
Careaga-Houck, M; Sprecher, H (1990) Effects of a fish oil diet on the metabolism of endogenous (n-6) and (n-3) fatty acids in rat neutrophils. Biochim Biophys Acta 1047:29-34
Garcia, M C; Sprecher, H; Rosenthal, M D (1990) Chain elongation of polyunsaturated fatty acids by vascular endothelial cells: studies with arachidonate analogues. Lipids 25:211-5
Mohammed, B S; Hagve, T A; Sprecher, H (1990) The metabolism of 20- and 22-carbon unsaturated acids in rat heart and myocytes as mediated by feeding fish oil. Lipids 25:854-8

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