Submitted on April 3, 2006
Revised on April 18, 2006
Accepted on April 20, 2006
Lysosomal metabolism of lipid-modified proteins
Jui-Yun Lu and Sandra L. Hofmann
Internal Medicine, University of Texas Southwestern Medicine Center, Dallas, TX 75390-8593
Corresponding Author: sandra.hofmann{at}utsouthwestern.edu
Much is now understood concerning the synthesis of prenylated and palmitoylated proteins, but what is known of their metabolic fate? This review details metabolic pathways for the lysosomal degradation of S-fatty acylated and prenylated proteins. Central to these pathways are two lysosomal enzymes, palmitoyl-protein thioesterase and prenylcysteine lyase. Palmitoyl-protein thioesterase is a soluble lipase that cleaves fatty acids from cysteine residues in proteins during lysosomal protein degradation. Notably, deficiency in the enzyme causes a neurodegenerative lysosomal storage disorder, infantile neuronal ceroid lipofuscinosis. Prenylcysteine lyase is a membrane-associated flavin-containing lysosomal monooxygenase that metabolizes prenylcysteine to prenyl aldehyde through a completely novel mechanism. The eventual metabolic fates of other lipidated proteins (such as glycosylphosphatidylinositol-anchored and N-myristoylated proteins) are poorly understood, suggesting directions for future research.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
