Identiˆcation and Expression of a Rat Fatty Acid Elongase Involved in the Biosynthesis of C 18 Fatty Acids

A major part of the palmitic acid (C16:0) generated by fatty acid synthase is converted into stearic acid (C18:0) via carbon chain elongation. Here, we describe the cloning and expression of a rat hepatic enzyme, rELO2, responsible for the elongation of C16:0, presumably at the condensing reaction. Heterologous expression experiments in a yeast, Saccharomyces cerevisiae, demonstrated the elongation activity of rELO2 on C16:0 and to a lesser extent, C18:0 and fatty acids with low desaturation degree. This was distinct from that rELO1, a rat homolog of HELO1, which preferably catalyzed the elongation of monoand polyunsaturated fatty acids of C16–C20. The Northern analysis showed that the expression of rELO2, but not rELO1, in hepatocytes was activated by the cycles of fasting and refeeding rats on a fat-free diet. Under these conditions, the rELO1 was expressed constitutively in various tissues but the rELO2 transcripts were detected predominantly in liver.

[1]  O. Suzuki,et al.  Production of arachidonic acid by filamentous fungus, Mortierella alliacea strain YN-15 , 2001 .

[2]  S. Larsen,et al.  Molecular aspects of β-ketoacyl synthase (KAS) catalysis , 2000 .

[3]  J. Dorado,et al.  Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids. , 2000, The Biochemical journal.

[4]  P. Shewry,et al.  Heterologous reconstitution in yeast of the polyunsaturated fatty acid biosynthetic pathway. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  P. Tvrdik,et al.  Role of a New Mammalian Gene Family in the Biosynthesis of Very Long Chain Fatty Acids and Sphingolipids , 2000, The Journal of cell biology.

[6]  Yung-Sheng Huang,et al.  Identification and characterization of an enzyme involved in the elongation of n6 and n-3 polyunsaturated fatty acids , 2000 .

[7]  H. Shimano,et al.  Sterol Regulatory Element-binding Protein-1 as a Key Transcription Factor for Nutritional Induction of Lipogenic Enzyme Genes* , 1999, The Journal of Biological Chemistry.

[8]  O. Suzuki,et al.  Molecular Cloning and Functional Characterization of Rat Δ-6 Fatty Acid Desaturase , 1999 .

[9]  I. Shimomura,et al.  Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[10]  D. Toke,et al.  ELO2 and ELO3, Homologues of theSaccharomyces cerevisiae ELO1 Gene, Function in Fatty Acid Elongation and Are Required for Sphingolipid Formation* , 1997, The Journal of Biological Chemistry.

[11]  H. Sprecher,et al.  Studies to determine if rat liver contains multiple chain elongating enzymes. , 1997, Biochimica et biophysica acta.

[12]  D. Toke,et al.  Isolation and Characterization of a Gene Affecting Fatty Acid Elongation in Saccharomyces cerevisiae* , 1996, The Journal of Biological Chemistry.

[13]  H. W. Cook.  Fatty acid desaturation and chain elongation in eukaryotes , 1996 .

[14]  D. W. James,et al.  Directed tagging of the Arabidopsis FATTY ACID ELONGATION1 (FAE1) gene with the maize transposon activator. , 1995, The Plant cell.

[15]  B. Fox,et al.  Membrane Bound Desaturases and Hydroxylases: Structure Function Studies , 1995 .

[16]  B. Fox,et al.  Eight histidine residues are catalytically essential in a membrane-associated iron enzyme, stearoyl-CoA desaturase, and are conserved in alkane hydroxylase and xylene monooxygenase. , 1994, Biochemistry.

[17]  Kay Hofmann,et al.  Tmbase-A database of membrane spanning protein segments , 1993 .

[18]  D. L. Cinti,et al.  The fatty acid chain elongation system of mammalian endoplasmic reticulum. , 1992, Progress in lipid research.

[19]  J. Lefkowith,et al.  Accelerated essential fatty acid deficiency by delta 9 desaturase induction: dissociation between the effects on liver and other tissues. , 1990, Biochimica et biophysica acta.

[20]  D. L. Cinti,et al.  Enzyme site-specific changes in hepatic microsomal fatty acid chain elongation in streptozotocin-induced diabetic rats. , 1990, Biochimica et biophysica acta.

[21]  C. Martín,et al.  Isolation and characterization of OLE1, a gene affecting fatty acid desaturation from Saccharomyces cerevisiae. , 1989, The Journal of biological chemistry.

[22]  D. L. Cinti,et al.  Effect of the peroxisomal proliferator di(2-ethylhexyl)phthalate on component reactions of the rat hepatic microsomal fatty acid chain elongation system and on other hepatic lipogenic enzymes. , 1986, Archives of biochemistry and biophysics.

[23]  D. L. Cinti,et al.  Evidence for multiple condensing enzymes in rat hepatic microsomes catalyzing the condensation of saturated, monounsaturated, and polyunsaturated acyl coenzyme A. , 1986, The Journal of biological chemistry.

[24]  P. Strittmatter,et al.  The induction and characterization of rat liver stearyl-CoA desaturase mRNA. , 1985, The Journal of biological chemistry.

[25]  H. Sprecher,et al.  An analysis of partial reactions in the overall chain elongation of saturated and unsaturated fatty acids by rat liver microsomes. , 1977, The Journal of biological chemistry.

[26]  H. Sprecher.  The influence of dietary alterations, fasting and competitive interactions on the microsomal chain elongation of fatty acids. , 1974, Biochimica et biophysica acta.

[27]  J. Volpe,et al.  Regulation of mammalian fatty-acid synthetase. The roles of carbohydrate and insulin. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[28]  D. Nugteren.  The enzymic chain elongation of fatty acids by rat-liver microsomes. , 1965, Biochimica et biophysica acta.

[29]  J. Folch,et al.  A simple method for the isolation and purification of total lipides from animal tissues. , 1957, The Journal of biological chemistry.