Because
X-linked adrenoleukodystrophy is treated using
erucic acid (22:1n-9), we assessed its metabolism in rat liver and heart following infusion of [14-(14)C]22:1n-9 (170 Ci/kg) under steady-state-like conditions. In liver, 2.3-fold more tracer was taken up as compared to heart, accounted entirely by increased incorporation into the organic fraction (4.2-fold). The amount of tracer entering the aqueous fraction, which represents beta-oxidation, was not different between groups; however a significantly elevated proportion of tracer was in the heart aqueous fraction. In both tissues, 76% of the radioactivity found in the organic fraction was esterified in neutral
lipids, while only about 10% was found esterified into
phospholipids. In liver, 56% of
lipid radioactivity was found in
cholesteryl esters, whereas in heart 64% was found in
triacylglycerols. Because 22:1n-9 can be chain shortened, we assessed tracer metabolism using phenacyl
fatty acid derivatives esterified from saponified esterified neutral
lipid (
triacylglycerol/
cholesteryl ester) and
phospholipid fractions. In heart esterified neutral
lipids, 75% of tracer was recovered as 22:1n-9 and only 10% as
oleic acid (18:1n-9), while in liver only 25% of the tracer was recovered as 22:1n-9, while 50% was found as
stearic acid (18:0) and 10% as 18:1n-9. In liver and heart
phospholipids, the tracer was distributed amongst the n-9
fatty acid family. Thus, 22:1n-9 under went tissue selective metabolism, with conversion to 18:0 the dominant pathway in the liver presumably for export in the neutral
lipids, while in heart it was found primarily as 22:1n-9 in neutral
lipids and used for beta-oxidation.