Fatty acid metabolism in marine fish: Low activity of fatty acyl Δ5 desaturation in gilthead sea bream ( Sparus aurata ) cells

Marine fish are known to have an absolute dietary requirement for C20 and C22 highly unsaturated fatty acids. Previous studies using cultured cell lines indicated that underlying this requirement in marine fish was either a deficiency in fatty acyl Δ5 desaturase or C18-20 elongase activity. Recently, Ghioni et al. (Biochim. Biophys. Acta, 1437, 170-181, 1999) presented evidence that in turbot cells there was low activity of C18-20 elongase whereas Δ5 desaturase had high activity. In the present study, the fatty acid desaturase/elongase pathway was investigated in a cell line (SAF-1) from another carnivorous marine fish, sea bream. The metabolic conversions of a range of radiolabelled polyunsaturated fatty acids that comprised the direct substrates for Δ6 desaturase ([1-14C]18:2n-6 and [1-14C]18:3n-3), C18-20 elongase ([U-14C]18:4n-3), Δ5 desaturase ([1-14C]20:3n-6 and [U-14C]20:4n-3) and C20-22 elongase ([1-14C]20:4n-6 and [1-14C]20:5n-3) were utilized. The results showed that fatty acyl Δ6 desaturase in SAF-1 cells was highly active and there was substantial C18-20 elongase and C20-22 elongase activities. A deficiency in the desaturation/elongation pathway was clearly identified at the level of the fatty acyl Δ5 desaturase which was very low, particularly with 20:4n-3 as substrate. In comparison, the apparent activities of Δ6 desaturase, C18-20 elongase and C20-22 elongase were approximately 94-fold, 27-fold and 16-fold greater than that for Δ5 desaturase towards their respective n-3 polyunsaturated fatty acid substrates. The evidence obtained in the SAF-1 cell line is consistent with the dietary requirement for C20 and C22 highly unsaturated fatty acids in the marine fish, the sea bream, being primarily due to a deficiency in fatty acid Δ5 desaturase activity

Cultured fish cells metabolize octadecapentaenoic acid (all-cis delta3,6,9,12,15–18∶5) to octadecatetraenoic acid (all-cis delta6,9,12,15–18∶4) via its 2-trans intermediate (trans delta2, all-cis delta6,9,12,15–18∶5)

Octadecapentaenoic acid (all-cis Δ3,6,9,12,15-18:5; 18:5n-3) is an unusual fatty acid found in marine dinophytes, haptophytes and prasinophytes. It is not present at higher trophic levels in the marine food web but its metabolism by animals ingesting algae is unknown. Here we studied the metabolism of 18:5n-3 in cell lines derived from turbot (Scophthalmus maximus), gilthead sea bream (Sparus aurata) and Atlantic salmon (Salmo salar). Cells were incubated in the presence of approximately 1 μM [U-14C] 18:5n-3 methyl ester or [U-14C] 18:4n-3 (octadecatetraenoic acid; all-cis Δ6,9,12,15-18:4) methyl ester, both derived from the alga Isochrysis galbana grown in H14CO3, and also with 25 μM unlabelled 18:5n-3 or 18:4n-3. Cells were also incubated with 25 μM trans Δ2, all-cis Δ6,9,12,15-18:5 (2-trans 18:5n-3) produced by alkaline isomerization of 18:5n-3 chemically synthesized from docosahexaenoic acid (all-cis Δ4,7,10,13,16,19-22:6; 22:6n-3). Radio- and mass analyses of total fatty acids extracted from cells incubated with 18:5n-3 were consistent with this fatty acid being rapidly metabolized to 18:4n-3 which was then elongated and further desaturated to eicosatetraenoic acid (all-cis Δ8,11,14,17,19-20:4; 20:4n-3) and eicosapentaenoic acid (all-cis Δ5,8,11,14,17-20:5; 20:5n-3). Similar mass increases of 18:4n-3 and its elongation and further desaturation products occurred in cells incubated with 18:5n-3 or 2-trans 18:5n-3. We conclude that 18:5n-3 is readily converted biochemically to 18:4n-3 via a 2-trans 18:5n-3 intermediate generated by a Δ3,Δ2-enoyl-CoA-isomerase acting on 18:5n-3. Thus, 2-trans 18:5n-3 is implicated as a common intermediate in the β-oxidation of both 18:5n-3 and 18:4n-3

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The effect of different cooking methods on proximate composition and lipid quality of rainbow trout (Oncorhynchus mykiss)

Summary In this study, the effects of frying, oven-baking, barbecuing, and smoking on the proximate composition and lipid quality of trout (Onchorhynchus mykiss) were studied. The proximate compositions were affected significantly by all cooking methods. An increase in the lipid content and a decrease in the moisture content were observed in all the cooking methods. A decrease in the protein content was found in barbecued and smoked samples, but not in fried or oven-baked, on dry-weight basis. Regarding the lipid quality, the free fatty acids (FFA, grams of oleic acid per 100-g lipid), peroxide values (POV, meq active oxygen per kg lipid), and thiobarbituric acid values (TBA, mg malonaldehydeper kg fish muscle) were analysed. The FFA contents in fresh, fried, oven-baked, barbecued and smoked trout on wet-weight basis were found to be 8.76, 0.76, 5.05, 0.81, and 9.44-g oleic acid per 100-g lipid, respectively. POV in fried, oven-baked, and barbecued samples increased significantly, while POV in smoked samples decreased significantly. An increase was observed in the TBA value in trout cooked with all methods. The results of this experiment showed that heating accelerates lipid oxidation. © 2007 The Author. Journal compilation 2007 Institute of Food Science and Technology Trust Fund