Selective accumulation of DHA

    

DHA is accumulated in brain preferentially over other tissues. The HUFA composition in brain does not respond readily to changed dietary amounts of omega-3 and omega-6 fatty acids. Two videocast lectures by Norman Salem Jr., Ph.D., NIAAA, give background information.

1."Essential fatty acids- different chain lengths and metabolism" - This is a primer on the structure and nomenclature of fatty acids for the non-specialist. It describes the chemistry, metabolism, and nature of omega-6 and omega-3 essential fatty acids in the context of more widely discussed saturated and unsaturated fats. The 18-carbon essential fatty acids can be metabolized to 20-carbon and 22-carbon forms that have different distributions in tissue membranes and have very different impacts on eicosanoid formation (see Eicosanoids ). http://videocast.nih.gov/ram/crii01c203202000.ram

2. "Metabolism and catabolism of DHA and AA in adults: clinical implications of alcohol and smoking" - This overview describes how chronic alcohol exposure decreases levels of 20:4n-6 and 22:6n-3 in animals and humans, even though it also increased the apparent incorporation of 18-carbon precursors. It is inadvisable to speculate about fatty acid metabolism based on compositional data only. http://videocast.nih.gov/ram/omega7.ram


    The in vivo capacity of human infants to convert 18 carbon essential fatty acids to their elongated and desaturated forms was shown with gas chromatography/negative chemical ionization/mass spectrometry employing H 2 labeled essential fatty, The in vivo conversion of linoleic acid (18:2n6) to arachidonic acid (20:4n6) demonstrated that all elongases/desaturases necessary for the conversion of linolenic acid (18:3n3) to docosahexaenoic acid (22:6n3) are also active in the first week after birth. These data clearly show that infants biosynthesize 22:6n3, although amounts produced in vivo from 18:3n3 may be inadequate to support the optimal neural development that is observed in breast fed infants. Salem N; Wegher B; Mena P; Uauy R. Arachidonic and docosahexaenoic acids are biosynthesized from their 18 carbon precursors in human infants. Proc Nat Acad Sci 1996; 93: 49 54.


    Elongation/desaturation of deuterated 2H5 linoleic acid (2H5 LA) to form arachidonic acid (AA), and 2H5 alpha linolenic acid (2H5 LNA) to form docosahexaenoic acid (DHA) was measured in19 preterm infants, 11 term, and 11 intrauterine growth retarded (IUGR) infants. Higher time integrated concentrations of 2H5 AA and 2H5 DHA were observed in preterm infants relative to the other two groups, and time integrated 2H5/2H0 ratios for AA and DHA formation were greater at earlier gestational ages. Growth retardation was associated with diminished formation of AA and DHA. Uauy R; Mena P; Wegher B; Nieto S; Salem N. Long chain polyunsaturated fatty acid formation in neonates: Effect of gestational age and intrauterine growth. PEDIATRIC RESEARCH 2000; 47: 127 135.


    Time course labeling experiments indicated that the intermediates, 20:5n 3 and 22:5n 3, may be converted to 22:6n 3 within the brain. A rise of labeled 22:6n 3 in the brain at 24 h appeared to be due to uptake of this fatty acid from the blood. Labeled 22:6n 3 in the brain continued to increase beyond 24 h in a way not correlated with its blood concentration. During development in the rodent, different regions within the brain may vary in their capacity to synthesize 22:6n 3, and this may be correlated with regional growth rates. Pawlosky RJ; Ward G; Salem N. Essential fatty acid uptake and metabolism in the developing rodent brain. LIPIDS 1996; 31: S103 S107


    Rhesus monkeys that were maintained on an adequate diet but with low levels of essential fatty acids (1.4 en% linoleic, 18:2n 6, and 0.08 en%, linolenic acid, 18:3n 3) had low 20:4n 6 and 22: 6n 3 in their livers, plasma lipoproteins, and erythrocytes during an 18 month period of alcohol exposure. Monkeys that consumed alcohol also had higher plasma 4 hydroxynonenal compared to controls, suggesting higher oxidative loss of fatty acids. Alcohol consumption did not appear to affect the absorption of deuterium labeled 2H5 18:2n 6 or 2H5 18:3n 3 ethyl esters into the circulation. However, there was a greater enrichment of deuterium in the biosynthesized 20:4n 6 and 22:6n 3 in the monkeys exposed to alcohol compared to controls. Chronic alcohol exposure may stimulate the rate at which long chain polyunsaturated fatty acids are biosynthesized to compensate for increased lipid peroxidation. Pawlosky RJ; Salem N. Alcohol consumption in rhesus monkeys depletes tissues of polyunsaturated fatty acids and alters essential fatty acid metabolism. ALCOHOLISM CLINICAL AND EXPERIMENTAL RESEARCH 1999; 23: 311 317.

Gas chromatography/negative chemical ionization mass spectrometry was employed for high sensitivity detection of the following isotopes: deuterium-labeled-linolenate, carbon-13-U-labeled-eicosapentaenoate, carbon-13-U-labeled-linoleate, and deuterium-labeled-dihomo-gamma-linolenate that were given to rats either singly or together in a single oral dose. Rat blood was collected after dosing, and the isotopomers of the precursors and their main metabolites, including those containing both(13) C and (2)H, were detected simultaneously with good resolution and without interference from other isotopes. Prostaglandins Leukot Essent Fatty Acids 2002 Aug-Sep;67(2-3):141-6 A technique for the in vivo study of multiple stable isotope-labeled essential fatty acids. Lin Y, Salem N Jr.