ABERRANT LIPIDS AND GLYCOPROTEINS IN CYSTIC FIBROSIS

Project Details

Description

In cystic fibrosis the symptoms of general obstruction of secretory organs
and gastrointestinal tract, chronic progressive lung incapacitation and
deranged transport of ions seem to be directly related to the modified
glycoproteins and lipids in this disease. The projected studies are aimed
to investigate the implications of the modified (overacylated with fatty
acids) glycoproteins and the presence of ether lipid analogs in cystic
fibrosis, to correlate the qualitative and quantitative results on lipids
and glycoproteins with the pathological observations, to study the
enzyme(s) involved in glycoprotein acylation (glycoprotein fatty acyl
transferase(s)) and enzymes involved in regulation of the content of ether
lipid analogs in the tissue (fatty acyl CoA reductase, fatty alcohol NAD+
oxidoreductase) and to correlate these findings with the health status of
the patient. Further objectives of this proposal are to design a simple
and reliable assay of fatty acyl transferase, or fatty acyl CoA reductase,
or fatty alcohol NAD+ oxidoreductase using readily available specimens of
the human tissue or fluids (skin biopsies, blood, amniotic fluid) which
might be adopted for screening and for diagnostic purposes. The mucus glycoprotein will be isolated by combination of the organic
solvent extraction, gel filtration and CsCl equilibrium density gradient
centrifugation, and then analyzed for the content of covalently bound fatty
acids. Using combination of chemical methods and proteases, the site(s) of
fatty acid substitution will be determined. The glycoprotein, after
release of fatty acids and deglycosylation, will be used as a substrate in
the fatty acyl transferase(s) assay. The lipids isolated from samples
prior to glycoprotein preparation will be separated into the individual
components by means of thin layer chromatography, followed by analyses for
the ether lipid analogs. Using palmitoyl (C14) CoA and (C14) hexadecanol
the activity of fatty acyl transferase(s), fatty acyl CoA reductase, and
fatty alcohol NAD+ oxidoreductase will be determined.
StatusFinished
Effective start/end date2/1/851/31/91

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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