Role of Oligosaccharides in the Pharmacokinetics of Tissue-Derived and Genetically Engineered Cholinesterases
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...
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| Veröffentlicht in: | Molecular pharmacology 1998-01, Vol.53 (1), p.112-122 |
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| creator | Saxena, Ashima Ashani, Yacov Raveh, Lily Stevenson, David Patel, Thakor Doctor, B.P. |
| description | 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 ∼1.0. ForTorpedo californica acetylcholinesterase, monomeric and tetrameric fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase, this ratio was ∼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-derivedT. 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. |
| doi_str_mv | 10.1124/mol.53.1.112 |
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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 ∼1.0. ForTorpedo californica acetylcholinesterase, monomeric and tetrameric fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase, this ratio was ∼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-derivedT. 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.</description><identifier>ISSN: 0026-895X</identifier><identifier>EISSN: 1521-0111</identifier><identifier>DOI: 10.1124/mol.53.1.112</identifier><identifier>PMID: 9443938</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acetylcholinesterase - blood ; Acetylcholinesterase - pharmacokinetics ; Animals ; Butyrylcholinesterase - blood ; Butyrylcholinesterase - pharmacokinetics ; Cattle ; Centrifugation, Density Gradient ; CHO Cells ; Cholinesterases - analysis ; Cholinesterases - blood ; Cholinesterases - pharmacokinetics ; Cricetinae ; Enzyme Stability ; Glycosylation ; Horses ; Humans ; Injections, Intravenous ; Mice ; Oligosaccharides - analysis ; Oligosaccharides - metabolism ; Recombinant Proteins - pharmacokinetics ; Torpedo</subject><ispartof>Molecular pharmacology, 1998-01, Vol.53 (1), p.112-122</ispartof><rights>1998 American Society for Pharmacology and Experimental Therapeutics</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c363t-54bec0e06892ed1a54aea0f9e4f52438aa5223fe1304cd21542f5757d93ea3343</citedby><cites>FETCH-LOGICAL-c363t-54bec0e06892ed1a54aea0f9e4f52438aa5223fe1304cd21542f5757d93ea3343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9443938$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saxena, Ashima</creatorcontrib><creatorcontrib>Ashani, Yacov</creatorcontrib><creatorcontrib>Raveh, Lily</creatorcontrib><creatorcontrib>Stevenson, David</creatorcontrib><creatorcontrib>Patel, Thakor</creatorcontrib><creatorcontrib>Doctor, B.P.</creatorcontrib><title>Role of Oligosaccharides in the Pharmacokinetics of Tissue-Derived and Genetically Engineered Cholinesterases</title><title>Molecular pharmacology</title><addtitle>Mol Pharmacol</addtitle><description>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 ∼1.0. ForTorpedo californica acetylcholinesterase, monomeric and tetrameric fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase, this ratio was ∼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-derivedT. 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.</description><subject>Acetylcholinesterase - blood</subject><subject>Acetylcholinesterase - pharmacokinetics</subject><subject>Animals</subject><subject>Butyrylcholinesterase - blood</subject><subject>Butyrylcholinesterase - pharmacokinetics</subject><subject>Cattle</subject><subject>Centrifugation, Density Gradient</subject><subject>CHO Cells</subject><subject>Cholinesterases - analysis</subject><subject>Cholinesterases - blood</subject><subject>Cholinesterases - pharmacokinetics</subject><subject>Cricetinae</subject><subject>Enzyme Stability</subject><subject>Glycosylation</subject><subject>Horses</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Mice</subject><subject>Oligosaccharides - analysis</subject><subject>Oligosaccharides - metabolism</subject><subject>Recombinant Proteins - pharmacokinetics</subject><subject>Torpedo</subject><issn>0026-895X</issn><issn>1521-0111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkM1PGzEQxa2qKITQG1ekvbSnbvDnZn2sQkorIYEQSNwsx57NGrzr1N5Q5b_HIRHiwGn89H7zxnoInRE8JYTyiy74qWBTslNf0JgISkpMCPmKxhjTqqyleDxGJyk9YUy4qPEIjSTnTLJ6jLq74KEITXHj3SokbUyro7OQCtcXQwvFbdadNuHZ9TA4k3bsvUtpA-UlRPcCttC9La7gzdbeb4tFv8owxGzN2-DzOw0QdYJ0io4a7RN8O8wJevi9uJ__Ka9vrv7Of12XhlVsKAVfgsGAq1pSsEQLrkHjRgJvBOWs1lpQyhogDHNjKRGcNmImZlYy0IxxNkE_9rnrGP5t8nnVuWTAe91D2CQ1k9WMSCEz-HMPmhhSitCodXSdjltFsNq1q3K7SjBFdirj54fczbID-w4f6sz-973fulX730VQ60N9Pqy2H3OqPQe5hBcHUSXjoDdg844ZlA3u8w-8Aheelq8</recordid><startdate>199801</startdate><enddate>199801</enddate><creator>Saxena, Ashima</creator><creator>Ashani, Yacov</creator><creator>Raveh, Lily</creator><creator>Stevenson, David</creator><creator>Patel, Thakor</creator><creator>Doctor, B.P.</creator><general>Elsevier Inc</general><general>American Society for Pharmacology and Experimental Therapeutics</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>199801</creationdate><title>Role of Oligosaccharides in the Pharmacokinetics of Tissue-Derived and Genetically Engineered Cholinesterases</title><author>Saxena, Ashima ; Ashani, Yacov ; Raveh, Lily ; Stevenson, David ; Patel, Thakor ; Doctor, B.P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c363t-54bec0e06892ed1a54aea0f9e4f52438aa5223fe1304cd21542f5757d93ea3343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Acetylcholinesterase - blood</topic><topic>Acetylcholinesterase - pharmacokinetics</topic><topic>Animals</topic><topic>Butyrylcholinesterase - blood</topic><topic>Butyrylcholinesterase - pharmacokinetics</topic><topic>Cattle</topic><topic>Centrifugation, Density Gradient</topic><topic>CHO Cells</topic><topic>Cholinesterases - analysis</topic><topic>Cholinesterases - blood</topic><topic>Cholinesterases - pharmacokinetics</topic><topic>Cricetinae</topic><topic>Enzyme Stability</topic><topic>Glycosylation</topic><topic>Horses</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Mice</topic><topic>Oligosaccharides - analysis</topic><topic>Oligosaccharides - metabolism</topic><topic>Recombinant Proteins - pharmacokinetics</topic><topic>Torpedo</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saxena, Ashima</creatorcontrib><creatorcontrib>Ashani, Yacov</creatorcontrib><creatorcontrib>Raveh, Lily</creatorcontrib><creatorcontrib>Stevenson, David</creatorcontrib><creatorcontrib>Patel, Thakor</creatorcontrib><creatorcontrib>Doctor, B.P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saxena, Ashima</au><au>Ashani, Yacov</au><au>Raveh, Lily</au><au>Stevenson, David</au><au>Patel, Thakor</au><au>Doctor, B.P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of Oligosaccharides in the Pharmacokinetics of Tissue-Derived and Genetically Engineered Cholinesterases</atitle><jtitle>Molecular pharmacology</jtitle><addtitle>Mol Pharmacol</addtitle><date>1998-01</date><risdate>1998</risdate><volume>53</volume><issue>1</issue><spage>112</spage><epage>122</epage><pages>112-122</pages><issn>0026-895X</issn><eissn>1521-0111</eissn><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 ∼1.0. ForTorpedo californica acetylcholinesterase, monomeric and tetrameric fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase, this ratio was ∼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-derivedT. 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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9443938</pmid><doi>10.1124/mol.53.1.112</doi><tpages>11</tpages></addata></record> |
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| ispartof | Molecular pharmacology, 1998-01, Vol.53 (1), p.112-122 |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Acetylcholinesterase - blood Acetylcholinesterase - pharmacokinetics Animals Butyrylcholinesterase - blood Butyrylcholinesterase - pharmacokinetics Cattle Centrifugation, Density Gradient CHO Cells Cholinesterases - analysis Cholinesterases - blood Cholinesterases - pharmacokinetics Cricetinae Enzyme Stability Glycosylation Horses Humans Injections, Intravenous Mice Oligosaccharides - analysis Oligosaccharides - metabolism Recombinant Proteins - pharmacokinetics Torpedo |
| title | Role of Oligosaccharides in the Pharmacokinetics of Tissue-Derived and Genetically Engineered Cholinesterases |
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