Skip to main content
Article thumbnail
Location of Repository

Transphosphatidylation of sugar alcohols and its implications for the pathogenesis of diabetic complications

By S. A. Lattimer, D. A. Greene and J. Nakamura

Abstract

Glucose-induced sorbitol accumulation and attendant alterations in cellular myo -inositol and phosphoinositide metabolism have been invoked in the pathogenesis of diabetic complications; however, direct effects of sorbitol on membrane phospholipid composition or metabolism have never been evaluated. Phospholipase D catalyses the transphosphatidylation of ethanol into phosphatidylcholine to yield phosphatidylethanol, an “abnormal” phospholipid whose content in rat brain is increased by chronic ethanol ingestion. Analogous transphosphatidylation of sorbitol or other polyols whose concentration is elevated in diabetes was explored in vitro and in glucose-exposed cultured human retinal pigment epithelial cells. Phosphatidylcholine and varying concentrations of sorbitol, galactitol, mannitol and glucose were incubated with peanut phospholipase D in sodium acetate buffer for varying time periods. Thin layer chromatography revealed new phospholipid bands whose hydrolysis by phospholipase D liberated a water-soluble compound that cochromatographed with sorbitol on gas-liquid chromatography, and whose concentration increased in a time- and concentration-dependent fashion. Identical transphosphatidylation activity was demonstrated in a rat brain synaptosomal fraction. Phospholipase D hydrolysis of lipids from human retinal pigment epithelial cells constitutively overexpressing the aldose reductase gene yielded a sorbitol-like compound whose appearance was increased by glucose exposure and was decreased by an aldose reductase inhibitor. Thus, glucose-induced aldose reductase inhibitor sensitive sorbitol accumulation might induce the formation of “phosphatidylsorbitol” through a transphosphatidyl mechanism that may contribute to altered membrane phospholipid metabolism in diabetes

Publisher: Springer-Verlag
Year: 1994
DOI identifier: 10.1007/BF00418379
OAI identifier: oai:deepblue.lib.umich.edu:2027.42/46032
Journal:
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://hdl.handle.net/2027.42/... (external link)
  • http://dx.doi.org/10.1007/BF00... (external link)
  • http://www.ncbi.nlm.nih.gov/si... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.