Effect of conjugated linoleic acid on Delta-5 desaturase activity in yeast transformed with fungal Delta-5 desaturase gene.
Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers derived from linoleic acid (LA: delta9, 12-18:2), has been shown to exhibit various biological functions based on studies using cell culture and animal models. It was postulated that the beneficial effects of CLA were exerted through suppression of production of arachidonic acid (AA; delta5,8,11,14-20:4) and consequently, production of pro-inflammatory eicosanoids. In this study, we used the baker's yeast, Saccharomyces cerevisiae, transformed with fungal delta5-desaturase gene as a model, to study whether CLA affects the activity of delta5-desaturase, a rate-limiting step which converts dihomo-gamma-linolenic acid (DGLA; delta8,11, 14-20:3) to AA. The activity of delta5-desaturase was examined in the transformed yeast incubated in a medium supplemented with DGLA and one of four different CLA isomers (c9, t11-, t10, c12-, c9, c11- and t9, t11). Results show that all four isomers were taken up readily by the yeast, and all of them suppressed the conversion of DGLA to AA. The degree of suppression, which varied significantly among four isomers was modulated by the level of CLA isomers added in the medium. Since portions of these CLA isomers could be converted to form delta5-CLA metabolites (delta5, c9, t11-, delta5, t10, c12-, delta5, c9, c11- and delta5, t9, t11-18:3), it is suggested that CLA suppressed the delta5-desaturation of DGLA to AA through substrate competition between DGLA and CLA isomers.
Chuang
Lu-Te
LT
Strategic-Discovery R&D, Ross Products Division, Abbott Laboratories, Columbus, OH 43215, USA.
Thurmond
Jennifer M
JM
Liu
Jim-Wen
JW
Mukerji
Pradip
P
Bray
Tammy M
TM
Huang
Yung-Sheng
YS
D016718:Arachidonic Acid / Q000378:metabolism; D002849:Chromatography, Gas; D000090943:Delta-5 Fatty Acid Desaturase; D004305:Dose-Response Relationship, Drug; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005821:Genetic Techniques; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D050356:Lipid Metabolism; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D000090943:Delta-5 Fatty Acid Desaturase; D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D016718:Arachidonic Acid; D044943:Fatty Acid Desaturases