Diversity in the ability of cultured cells to elongate and desaturate essential (n-6 and n-3) fatty acids.
Essential fatty acids (EFAs) cannot be synthesized by mammalian cells. Once taken in with the diet, they can undergo desaturations/saturations and chain elongations/shortenings to yield a variety of polyunsaturated fatty acids of the same family. Cells in vitro from a variety of tissues are capable of processing EFAs to varying extents. Conversion of the parent EFAs, linoleic (LA, n-6) and alpha-linolenic (LNA, n-3) acids, to the 20-carbon polyunsaturated fatty acids, arachidonic (AA, n-6) and eicosapentanoic (EPA, n-3), requires chain elongation and delta 6 and delta 5 desaturations. AA and EPA are required by many tissues for optimal biological function and are precursors of biologically active eicosanoid hormones. All cultured cells are able to elongate exogenous LA and LNA, and most can perform delta 5 desaturation, so delta 6 desaturation is the limiting step in AA and EPA production. Longer fatty acids that have more double bonds than AA or EPA are less frequently produced due to a deficiency in delta 4 desaturating ability. The process of retroconversion (chain shortening) is less extensively studied, but evidence from a variety of cells suggests that this type of metabolic conversion is normally active. The example of MCF-7 (human breast cancer cell line) and MCF-10A cells (human noncancerous breast cell line) is discussed in order to emphasize the diversity in EFA processing ability of cultured cells. Under identical culture conditions, MCF-10A cells perform extensive desaturations, elongations, and retroconversions, whereas MCF-7 cells can only elongate and retroconvert exogenous EFAs. Given the great diversity in the ability of cultured cells to process EFAs, no conclusions can be drawn regarding the mechanisms responsible for the effects of exogenous EFAs on a particular cell until that cell's EFA processing patterns have been evaluated.
Grammatikos
S I
SI
Department of Chemical Engineering, Northwestern University, Evanston, Illinois 60208-3120.
Subbaiah
P V
PV
Victor
T A
TA
Miller
W M
WM
D000818:Animals; D001711:Biotransformation; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D002478:Cells, Cultured; D003579:Cytochrome Reductases / Q000378:metabolism; D042966:Cytochrome-B(5) Reductase; D015786:Cytochromes b5 / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005228:Fatty Acids, Essential / Q000737:chemistry / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D009928:Organ Specificity
D005228:Fatty Acids, Essential; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D009363:Neoplasm Proteins; D015786:Cytochromes b5; D044943:Fatty Acid Desaturases; D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase