Deuterium-containing fatty acids

Early success in the study of natural membranes was attained by the use of the relatively simple organism Acholeplasma laidlawii (6-8). It has a single membrane, the plasma membrane, and will accept deuterium labelled fatty acids from a growth medium without significant alterations. For some cases enrichment of the membrane lipids to greater than 90% deuterium containing fatty acids can be achieved by use of the protein avidin in the growth medium (8). 

The amount of disorder in the fatty acid side chains in a phospholipid bilayer, as a function of temperature. The side chains become much more disordered as the temperature increases through the 7m. The solid curve represents a bilayer that does not contain cholesterol the dotted curve, a bilayer with the same phospholipid plus about 25% cholesterol. The amount of random, disorderly motion of the fatty acid chains can be measured quantitatively by deuterium- or l3C-NMR. At any given temperature, the disorder is greater near the tips of the chains (toward the middle of the bilayer) than it is close to the head-groups. 

Further investigation of the complex fragmentation behaviour of the steroid [M — H] ions led to the study of simpler model systems, viz. fatty acid esters containing a para-hydroxybenzyl (cf. 138, Scheme 37) or /3-(para-hydroxy)phenethyl moiety . Again, the formation of intermediate anion/molecule complexes was demonstrated by the course of collision-induced dissociation of various deuterium-labelled [M — ions, where... 

The hypothesis that branched amino acids are metabolized to branched fatty acids via a-keto acid intermediates is further supported by incubations with deuterated 2-oxo-3-methylpentanoate and 2-oxo-4-methylpentanoate/ the transamination products of lie and Leu respectively. GC/MS of acyl groups resulting from incubation with d2 -2-oxo-4-methylpentanoate (deuterated at C-3) revealed deuterium incorporation into glucose esters containing d2-3-methylbutyrate and d2-9-methyldecanoate. Trace amounts of d2-7-methyloctanoate were also observed, supporting the hypothesis that branched chain precursors are elongated by the addition of acetate. 

Rakoff, H. (1982) Preparation of Fatty Acids and Esters Containing Deuterium, Prog. Lipids Res. 21, 225-254. 

Bloch and Rittenberg (1942a, b) found that when deuterium-labeled acetate was fed to rats and mice the cholesterol isolated from these animals contained more deuterium than would be expected if the acetate had first been converted to water or to higher fatty acids. It was apparent that the administered deuterio-... 

Substitution of the stable hydrogen isotope of mass 2, deuterium (H or D), for hydrogen in a fatty acid minimizes the objection raised above in the use of unphysiological fatty acids. But since the mass of deuterium is twice that of hydrogen, compounds containing the heavy isotope may not behave like those cont ining the lighter isotope. For example, there is evidence to indicate that H2O, D2O, and HDO do not diffuse across the cell membrane at the same rate and do not enter into chemical reactions in precisely the same way. The difference in reaction... 

We have, however, been unable to demonstrate a difference in conformation of the carbohydrate moiety of C 18 l and C 22 l fatty acid containing Gbs by deuterium NMR [21],... 

The general method of van Heyningen etdl. 1938) for labeling fatty acids with deuterium may be applied. By this mediod, it is possible to obtain 36% of the equilibrium amoimt of tritium in the fa acid. Both H -palmitic acid and H -stearic acid have been prepared by this method. Tritiated stearic acid has also been prepared by the hydrogenation of Unoleic acid in ethylacetate containing H2 0, hydrogen, and platinum catalyst. 

After keeping mice on a stock diet containing 20% deuterated linseed oil for three days, the liver phosphatide fatty acids were found, by Barrett and his associates (21), to contain nearly three times as much deuterium as body phosphatides. 

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