Trans-vaccenate is Δ13-desaturated by FADS3 in rodents.
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.
Laboratoire de Biochimie-Nutrition Humaine, Agrocampus Ouest-Institut National de la Recherche Agronomique (INRA) USC2012, Rennes, France.
Vincent
V
Rioux
Frédérique
F
Pédrono
Hélène
H
Blanchard
Cécile
C
Duby
Nathalie
N
Boulier-Monthéan
Laurence
L
Bernard
Erwan
E
Beauchamp
Daniel
D
Catheline
Philippe
P
Legrand
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D044943:Fatty Acid Desaturases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D022781:Hepatocytes / Q000378:metabolism; D007536:Isomerism; D008969:Molecular Sequence Data; D009829:Oleic Acids / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity
D009829:Oleic Acids; D044943:Fatty Acid Desaturases; C000588954:FADS3 protein, rat; C050413:11-octadecenoic acid
FADS cluster; conjugated linoleic acid; desaturase activity; fatty acid desaturase; rumenic acid; trans-vaccenic acid; trans11,cis13-octadecadienoic acid