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June Lee, Xiaodong Jiao, J. Fielding Hejtmancik, Muriel Kaiser-Kupfer, William A. Gahl, Thomas C. Markello, Juanru Guo, Gerald J. Chader; The Metabolism of Fatty Acids in Human Bietti Crystalline Dystrophy. Invest. Ophthalmol. Vis. Sci. 2001;42(8):1707-1714.
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purpose. To investigate the role of abnormal lipid metabolism in Bietti
methods. Cultured human lymphocytes and fibroblasts from patients with Bietti
crystalline dystrophy (BCD) were incubated in the presence of[ 14C]18:3n-3 or [14C]18:2n-6. Incorporation
into the cellular lipid pools and further metabolism by desaturation or
elongation were monitored by thin-layer chromatography and HPLC.
Results were compared with those in normal control subjects and
patients with Wolman disease (WD).
results. Pulse–chase experiments with labeled fatty acids in all groups showed
that, after 1 hour, radioactivity was largely confined to the
triacylglyceride (TG) and choline phosphoglyceride (CPG) pools.
However, after several hours, radioactivity was transferred from the TG
and CPG pools, some going to the serine and ethanolamine
phosphoglyceride (SPG and EPG) pools. Fibroblasts from all groups
showed direct transfer of fatty acids (FAs) into CPG and EPG.
Incorporation of labeled FAs into the EPG pool paralleled extensive
desaturation and elongation of 18:2n-6 to 22:5n-6 and 18:3n-3 to
22:6n-3. Fibroblasts from patients with WD (a lysosomal acid lipase
deficiency characterized by excessive lipid accumulation), showed
higher incorporation of 18:2n-6 into TGs than did normal or BCD
fibroblasts. Conversely, fibroblasts from patients with BCD showed
lower conversion of 18:3n-3, but not of 18:2n-6, into polyunsaturated
FAs (PUFAs) than those of normal subjects or patients with WD. This was
true for total FAs, CPGs, and EPGs. Similar results were found in both
fibroblasts and lymphocytes; however, unlike fibroblasts, lymphocytes
from normal subjects showed similar levels of incorporation of FAs into
EPGs and CPGs. In contrast, incorporation of 18:3n-3 into EPGs was
decreased in lymphocytes from patients with BCD.
conclusions. BCD is characterized by a lower than normal conversion of FA precursors
into n-3 PUFA, whereas there is a higher than normal level of n-6 and
n-3 FAs incorporation into TGs in cells from patients with WD. These
findings raise the possibility that abnormal lipid metabolism
associated with BCD is the result of deficient lipid binding,
elongation, or desaturation in contrast to the lysosomal acid lipase
deficiency found in Wolman disease.
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