Biochemical and molecular studies of the polyunsaturated fatty acid desaturation pathway in 1 fish 2 3 4

23 24 Fish have an absolute dietary requirement for certain polyunsaturated fatty acids (PUFA) 25 termed " essential fatty acids " (EFA) that include members of both the n-6 and n-3 series 26 typified by linoleic acid, 18:2n-6, and α-linolenic acid, 18:3n-3. However, the biologically 27 active forms of EFA are generally the C 20 and C 22 metabolites of 18:2n-6 and 18:3n-3, viz. PUFA through a series of alternating desaturation and chain elongation reactions mediated by 30 microsomal systems containing elongases and Δ6 and Δ5 fatty acid desaturases. In species 31 that cannot perform these conversions, the C 20 and C 22 PUFA themselves are dietary EFA 32 and their C 18 homologues do not satisfy EFA requirements. The extent to which the foregoing 33 statements apply quantitatively to a given fish species varies widely. Therefore, a vital area in 34 lipid nutrition in fish is the provision of sufficient amounts of the correct EFA to satisfy the 35 requirements for normal growth and development, requirements that can vary quantitatively 36 during the life of the fish and are particularly important factors in larval marine fish. This 37 paper reviews the work on defining and characterising the fatty acid desaturation and 38 elongation pathway in fish. Biochemical studies have been advanced by the use of cell 39 cultures which have elucidated key parts of the pathway. Thus, the presence of the so-called 40 Sprecher shunt, where 22:6n-3 is produced from 20:5n-3 through two successive elongations 41 and a Δ6 desaturase followed by peroxisomal chain shortening, was demonstrated in trout. 42 Similarly, the block in the pathway in marine and/or piscivorous fish could be due to either a 43 deficiency of C 18-20 elongase or Δ5 desaturase and this varies between different marine 44 species. Recent work has focussed on the molecular biology of the pathway with the cloning 45 of fatty acid desaturases and elongases from a variety of fish species. Zebrafish have been 46 used as a model species and a unique desaturase possessing both Δ6 and Δ5 activity along 47 with an elongase with very high C 18-20 activity have been cloned and characterised. 48 Understanding this pathway is of increased importance due to the current dependence of 49 salmonid and marine fish aquaculture on fish oil, the supply of which is becoming 50 increasingly limited and unsustainable, necessitating the use in fish feeds of sustainable plant …