Saxena_1998_Mol.Pharmacol_53_112

Reference

Title : Role of oligosaccharides in the pharmacokinetics of tissue-derived and genetically engineered cholinesterases - Saxena_1998_Mol.Pharmacol_53_112
Author(s) : Saxena A , Ashani Y , Raveh L , Stevenson D , Patel T , Doctor BP
Ref : Molecular Pharmacology , 53 :112 , 1998
Abstract :

To understand the role of glycosylation in the circulation of cholinesterases, we compared the mean residence time of five tissue-derived and two recombinant cholinesterases (injected intravenously in mice) with their oligosaccharide profiles. Monosaccharide composition analysis revealed differences in the total carbohydrate, galactose, and sialic acid contents. The molar ratio of sialic acid to galactose residues on tetrameric human serum butyrylcholinesterase, recombinant human butyrylcholinesterase, and recombinant mouse acetylcholinesterase was found to be approximately 1.0. For Torpedo californica acetylcholinesterase, monomeric and tetrameric fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase, this ratio was approximately 0.5. However, the circulatory stability of cholinesterases could not be correlated with the sialic acid-to-galactose ratio. Fractionation of the total pool of oligosaccharides obtained after neuraminidase digestion revealed one major oligosaccharide for human serum butyrylcholinesterase and three or four major oligosaccharides in other cholinesterases. The glycans of tetrameric forms of plasma cholinesterases (human serum butyrylcholinesterase, fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase) clearly demonstrated a reduced heterogeneity and higher maturity compared with glycans of monomeric fetal bovine serum acetylcholinesterase, dimeric tissue-derived T. californica acetylcholinesterase, and recombinant cholinesterases. T. californica acetylcholinesterase, recombinant cholinesterases, and monomeric fetal bovine serum acetylcholinesterase showed a distinctive shorter mean residence time (44-304 min) compared with tetrameric forms of plasma cholinesterases (1902-3206 min). Differences in the pharmacokinetic parameters of cholinesterases seem to be due to the combined effect of the molecular weight and charge- and size-based heterogeneity in glycans.

PubMedSearch : Saxena_1998_Mol.Pharmacol_53_112
PubMedID: 9443938

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Citations formats

Saxena A, Ashani Y, Raveh L, Stevenson D, Patel T, Doctor BP (1998)
Role of oligosaccharides in the pharmacokinetics of tissue-derived and genetically engineered cholinesterases
Molecular Pharmacology 53 :112

Saxena A, Ashani Y, Raveh L, Stevenson D, Patel T, Doctor BP (1998)
Molecular Pharmacology 53 :112