Publications

• cDNA cloning and characterization of human Delta5-desaturase involved in the biosynthesis of arachidonic acid.

  Leonard A.E., Kelder B., Bobik E.G., Chuang L.-T., Parker-Barnes J.M., Thurmond J.M., Kroeger P.E., Kopchick J.J., Huang Y.-S., Mukerji P.

  Two human expressed sequence tag (EST) cDNA sequences with identity with Delta(5)- and Delta(6)-desaturases from a filamentous fungus, Mortierella alpina, were identified from the LifeSeq(R) database of Incyte Pharmaceuticals, Inc. (Palo Alto, CA, U.S.A.). An oligonucleotide complementary to the 3 ... >> More

  Two human expressed sequence tag (EST) cDNA sequences with identity with Delta(5)- and Delta(6)-desaturases from a filamentous fungus, Mortierella alpina, were identified from the LifeSeq(R) database of Incyte Pharmaceuticals, Inc. (Palo Alto, CA, U.S.A.). An oligonucleotide complementary to the 3' EST cDNA sequences was used to screen human liver cDNA using rapid amplification of cDNA ends (RACE)-PCR. The amplified DNA fragment had 98% identity with a putative open reading frame (ORF) predicted from a human genomic sequence, and encoded 444 amino acids. Expression of this ORF in mouse fibroblast cells demonstrated that the encoded protein was a Delta(5)-desaturase, as determined by the conversion of dihomo-gamma-linolenic acid (C(20:3,n-6)) into arachidonic acid (C(20:4,n-6)). The human Delta(5)-desaturase contained a predicted N-terminal cytochrome b(5)-like domain, as well as three histidine-rich domains. A tissue expression profile revealed that this gene is highly expressed in fetal liver, fetal brain, adult brain and adrenal gland. A search of the existing databases led to localization of this ORF within a 14 kb interval flanked by the flap endonuclease-1 (FEN1) and vitelliform macular dystrophy (Best's disease; VMD2) loci of chromosome 11q12. << Less

  Biochem. J. 347:719-724(2000) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• Cloning, expression, and fatty acid regulation of the human Delta-5 desaturase.

  Cho H.P., Nakamura M., Clarke S.D.

  Arachidonic (20:4(n-6)), eicosapentaenoic (20:5(n-3)), and docosahexaenoic (22:6(n-3)) acids are major components of brain and retina phospholipids, substrates for eicosanoid production, and regulators of nuclear transcription factors. One of the two rate-limiting steps in the production of these ... >> More

  Arachidonic (20:4(n-6)), eicosapentaenoic (20:5(n-3)), and docosahexaenoic (22:6(n-3)) acids are major components of brain and retina phospholipids, substrates for eicosanoid production, and regulators of nuclear transcription factors. One of the two rate-limiting steps in the production of these polyenoic fatty acids is the desaturation of 20:3(n-6) and 20:4(n-3) by Delta-5 desaturase. This report describes the cloning and expression of the human Delta-5 desaturase, and it compares the structural characteristics and nutritional regulation of the Delta-5 and Delta-6 desaturases. The open reading frame of the human Delta-5 desaturase encodes a 444-amino acid peptide which is identical in size to the Delta-6 desaturase and which shares 61% identity with the human Delta-6 desaturase. The Delta-5 desaturase contains two membrane-spanning domains, three histidine-rich regions, and a cytochrome b(5) domain that all align perfectly with the same domains located in the Delta-6 desaturase. Expression of the open reading frame in Chinese hamster ovary cells instilled the ability to convert 20:3(n-6) to 20:4(n-6). Northern analysis revealed that many human tissues including skeletal muscle, lung, placenta, kidney, and pancreas expressed Delta-5 desaturase mRNA, but Delta-5 desaturase was most abundant in the liver, brain, and heart. However, in all tissues, the abundance of Delta-5 desaturase mRNA was much lower than that observed for the Delta-6 desaturase. When rats were fed a diet containing 10% safflower oil or menhaden fish oil, the level of hepatic mRNA for Delta-5 and Delta-6 desaturase was only 25% of that found in the liver of rats fed a fat-free diet or a diet containing triolein. Finally, a BLAST and Genemap search of the human genome revealed that the Delta-5 and Delta-6 desaturase genes reside in reverse orientation on chromosome 11 and that they are separated by <11,000 base pairs. << Less

  J. Biol. Chem. 274:37335-37339(1999) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Trans-vaccenate is Delta13-desaturated by FADS3 in rodents.

  Rioux V., Pedrono F., Blanchard H., Duby C., Boulier-Monthean N., Bernard L., Beauchamp E., Catheline D., Legrand P.

  Fatty acid desaturases play critical roles in regulating the biosynthesis of unsaturated fatty acids in all biological kingdoms. As opposed to plants, mammals are so far characterized by the absence of desaturases introducing additional double bonds at the methyl-end site of fatty acids. However, ... >> More

  Fatty acid desaturases play critical roles in regulating the biosynthesis of unsaturated fatty acids in all biological kingdoms. As opposed to plants, mammals are so far characterized by the absence of desaturases introducing additional double bonds at the methyl-end site of fatty acids. However, the function of the mammalian fatty acid desaturase 3 (FADS3) gene remains unknown. This gene is located within the FADS cluster and presents a high nucleotide sequence homology with FADS1 (Δ5-desaturase) and FADS2 (Δ6-desaturase). Here, we show that rat FADS3 displays no common Δ5-, Δ6- or Δ9-desaturase activity but is able to catalyze the unexpected Δ13-desaturation of trans-vaccenate. Although there is no standard for complete conclusive identification, structural characterization strongly suggests that the Δ11,13-conjugated linoleic acid (CLA) produced by FADS3 from trans-vaccenate is the trans11,cis13-CLA isomer. In rat hepatocytes, knockdown of FADS3 expression specifically reduces trans-vaccenate Δ13-desaturation. Evidence is presented that FADS3 is the first "methyl-end" fatty acid desaturase functionally characterized in mammals. << Less

  J. Lipid Res. 54:3438-3452(2013) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.