Library Faculty/Staff Scholarship and Research

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    Differences in the regulation of biosynthesis of 20- versus 22-carbon polyunsaturated fatty acids
    (Elsevier, 1995) Sprecher, H.W,; Baykousheva, S.P.; Luthria, D.L.; Mohammed, B.S.
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    The long road from chemistry, to microbiology, to information science
    (American Chemical Society, 1999) Baykoucheva, S
    People with nontraditional careers usually find it difficult to explain to others what has driven them through all their professional choices. With an MS in phys. chem., a PhD in microbiology (both earned in Bulgaria), and postdoctoral training, why would someone also translate scientific abstracts and papers, and even a book. Why would a fellow of the International Atomic Energy Agency, while specializing in Paris in the use of isotopes in biochemistry, also write articles about contemporary French intellectuals. Why would a researcher in Ohio State University, while trying to elucidate a metabolic pathway for beta-oxidation of arachidonic acid in peroxisomes, also earn an M.L.S. from Kent State University. Was it only the fascination with chemistry, microbiology, literature, history, linguistics, or the essays published by Eugene Garfield in "Current Contents," that led to a rewarding new career as an information professional and manager of ACS Library.
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    Pathways for the biosynthesis of polyunsaturated fatty acids
    (1996) Sprecher, Howard; Luthria, Devanand; Baykousheva, Svetla P.; Mohammed, Selma B.
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    Peroxisomal-microsomal communication in unsaturated fatty acid metabolism
    (Elsevier, 1995) Baykousheva, Svetla P.; Luthria, Devanand L.; Sprecher, Howard
    The addition of 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) to peroxisomes decreased the production of acid-soluble radioactivity formed by β-oxidation of [1-14C]arachidonate due to substrate removal by esterification into the acceptor. This peroxisomal-associated acyl-CoA:1-acyl-GPC acyltransferase activity was due to microsomal contamination. The production of acid-soluble radioactivity from [1-14C]7,10,13,16–22:4, but not from [3-14C]7,10,13,16–22:4 was independent of 1-acyl-GPC, with and without microsomes. By comparing rates of peroxisomal β-oxidation with those for microsomal acylation, it was shown that the preferred metabolic fate of arachidonate, when added directly to incubations, or generated via β-oxidation, was esterification by microsomal 1-acyl-GPC acyltransferase, rather than continued peroxisomal β-oxidation.
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    Metabolism of [1-14C]linoleic acid in human promyelocytic leukemia HL-60 cells grown and differentiated in serum-free medium
    (1993) Baykousheva, Svetla
    The metabolism of [1-14C]linoleic acid (LA) was studied in human promyelocytic leukemia cell line HL-60, grown and differentiated in serum-free medium. Both undifferentiated and dibutyryl cAMP-differentiated HL-60 cells exhibited similar patterns of conversion of LA to 4 other major fatty acids (i.e., 18:3, 20:3, 20:4, and 22:4).
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    The role played by β-oxidation in unsaturated fatty acid biosynthesis
    (1994) Sprecher, Howard; Baykousheva, Svetla
    The authors hypothesized that a role for peroxisomes might be to chain shorten fatty acids but that the products would be transported to the endoplasmic reticulum where they would be esterified into lipids. Results showed that when microsomes and 1-acyl-sn-glycero-3-phosphocholine are added to peroxisomes that competing reactions take place, i.e. β-oxidn. and esterification.
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    Arachidonic acid formed by peroxisomal β-oxidation of 7,10,13,16- docosatetraenoic acid is esterified into 1-acyl-sn-glycero-3-phosphocholine by microsomes
    (American Society for Biochemistry and Molecular Biology, Inc., 1994) Baykousheva, S. P.; Luthria, D. L.; Sprecher, H.
    Peroxisomal beta-oxidation of linoleic acid and arachidonic acid was depressed when 1-palmitoyl-sn-glycero-3-phosphocholine and microsomes were included in incubations. This reduction was due to the esterification of the substrate into the acceptor by microsomal 1-acyl-sn-glycero-3- phosphocholine acyltransferase. The first cycle of the beta-oxidation of 7,10,13,16-docosatetraenoic acid was independent of 1-acyl-sn-glycero-3-phosphocholine and microsomes. However, when arachidonate was produced it was esterified rather than serving as a substrate for continued beta-oxidation. When arachidonate and linoleate were incubated with peroxisomes alone, 2-trans-4,7,10-hexadecatetraenoic acid and 2-trans-4-decadienoic acid were the respective end products of beta-oxidation. 2-Oxo-8,11-heptadecadienone, a catabolite produced from linoleate, was most likely a nonenzymatic decarboxylation product of 3-oxo-9,12-octadecadienoic acid. In addition to the termination of beta-oxidation by microsomal-peroxisomal communication, our results with linoleate and arachidonate suggest that the reaction catalyzed by 2-trans-4-cis-dienoyl-CoA reductase is the control step in double bond removal. In addition, the beta-ketothiolase step may play a regulatory role in the peroxisomal beta-oxidation of linoleate but not arachidonate or 7,10,13,16-docosatetraenoic acid.
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    Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids
    (American Society for Biochemistry and Molecular Biology, Inc., 1995) Sprecher, H; Luthria, D. L..; Mohammed, B. S.; Baykousheva, S. P.
    Recent studies refute the commonly accepted, but untested, hypothesis that 7,10,13,16-22:4 and 7,10,13,16,19-22:5 are desaturated at position 4 by a microsomal acycl-CoA-independent desaturase. The synthesis of 4,7,10,13,16,19-22:6 occurs via the following reaction sequence: 4,7,10,13,16,19-22:6. The synthesis of 4,7,10,10,13,16-22:5 from 7,10,13,16-22:4 takes place via an analogous pathway. According to these pathways the 24-carbon acids that are made in the endoplasmic reticulum move to a site for partial beta-oxidation, 4,7,10,13,16-22:5 and 4,7,10,13,16,19-22:6, then move back to the endoplasmic reticulum where they are used as substrates for membrane lipid biosynthesis. The ability of fatty acid to serve as a substrate for continued peroxisomal beta-oxidation, versus its transfer out of peroxisomes for subsequent endoplasmic reticulum-associated esterification reactions, may be an important control for regulating membrane lipid fatty acid composition. Indeed, the revised pathways of polyunsaturated fatty acid biosynthesis imply that there is considerable intracellular movement endoplasmic reticulum. In addition, these revised pathways require that two 18-carbon and two 24-carbon acids are substrates for desaturation at position 6. Also, as linoleate and linolenate are metabolized, respectively, to 6,9,12,15,18-24:5 and 6,9,12,15,18,21-24:6, three n-6 acids and three n-3 acids are substrates for malonyl-CoA dependent chain elongation. It remains to be determined how many microsomal enzymes ancillary enzymes are expressed in tissues whose membrane lipids accumulate very long-chain polyunsaturated acids with up to 36 carbon atoms.
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    Regulation of the biosynthesis of 4,7,10,13,16-docosapentaenoic acid
    (1997) Mohammed, B. S.; Luthria, D. L.; Baykousheva, S. P.; Sprecher, H.
    It is now established that fatty acid 7,10,13,16-22:4 is metabolized into 4,7,10,13,16-22:5 as follows: 7,10,13,16-22:4-->9,12,15, 18-24:4-->6,9,12,15,18-24:5-->4,7,10,13,16-22:5. Neither C24 fatty acid was esterified to 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) by microsomes, whereas the rates of esterification of 4, 7,10,13,16-22:5, 7,10,13,16-22:4 and 5,8,11,14-20:4 were respectively 135, 18 and 160 nmol/min per mg of microsomal protein. About four times as much acid-soluble radioactivity was produced when peroxisomes were incubated with [3-14C]9,12,15,18-24:4 compared with 6,9,12,15,18-24:5. Only [1-14C]7,10,13,16-22:4 accumulated when [3-14C]9,12,15,18-24:4 was the substrate, but both 4,7,10,13,16-22:5 and 2-trans-4,7,10,13,16-22:6 were produced from [3-14C]6,9,12,15, 18-24:5. When the two C24 fatty acids were incubated with peroxisomes, microsomes and 1-acyl-GPC there was a decrease in the production of acid-soluble radioactivity from [3-14C]6,9,12,15, 18-24:5, but not from [3-14C]9,12,15,18-24:4. The preferential fate of [1-14C]4,7,10,13,16-22:5, when it was produced, was to move out of peroxisomes for esterification into the acceptor, whereas only small amounts of 7,10,13,16-22:4 were esterified. By using 2H-labelled 9,12,15,18-24:4 it was shown that, when 7,10,13,16-22:4 was produced, its primary metabolic fate was degradation to yield esterified arachidonate. Collectively, the results show that an inverse relationship exists between rates of peroxisomal beta-oxidation and of esterification into 1-acyl-GPC by microsomes. Most importantly, when a fatty acid is produced with its first double bond at position 4, it preferentially moves out of peroxisomes for esterification to 1-acyl-GPC by microsomes, rather than being degraded further via a cycle of beta-oxidation that requires NADPH-dependent 2,4-dienoyl-CoA reductase.