Reversible defects in O-linked glycosylation and LDL receptor expression in a UDP-Gal/UDP-GalNAc 4-epimerase deficient mutant

Cell. 1986 Mar 14;44(5):749-59. doi: 10.1016/0092-8674(86)90841-x.


We previously isolated an unusual hamster cell mutant (ldlD) that does not express LDL receptor activity unless it is cocultivated with other cells or grown in high concentrations of serum. We now show that ldlD cells are deficient in the enzyme UDP-galactose and UDP-N-acetylgalactosamine (GalNAc) 4-epimerase. When ldlD cells are grown in glucose-based media, they cannot synthesize enough UDP-galactose and UDP-GalNAc to allow normal synthesis of glycolipids and glycoproteins. The 4-epimerase deficiency accounts for all glycosylation defects previously observed in ldlD cells, including production of abnormal LDL receptors. All abnormal phenotypes of ldlD cells can be fully corrected by exogenous galactose and GalNAc. The separate effects of these sugars on LDL receptor activity suggest that O-linked carbohydrate chains are crucial for receptor stability. ldlD cells may be useful for structural and functional studies of many proteins, proteoglycans, and glycolipids containing galactose or GalNAc.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbohydrate Epimerases / deficiency*
  • Cell Line
  • Cricetinae
  • Genetic Complementation Test
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Isomerases / deficiency*
  • Protein Processing, Post-Translational*
  • Racemases and Epimerases / deficiency*
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism*
  • Structure-Activity Relationship
  • UDPglucose 4-Epimerase / deficiency*
  • Uridine Diphosphate Galactose / deficiency
  • Uridine Diphosphate N-Acetylgalactosamine / deficiency


  • Glycoproteins
  • Receptors, LDL
  • Uridine Diphosphate Galactose
  • Uridine Diphosphate N-Acetylgalactosamine
  • Isomerases
  • Racemases and Epimerases
  • Carbohydrate Epimerases
  • UDPglucose 4-Epimerase