FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Biochemistry1997; 36(24); 7481-7489; doi: 10.1021/bi963156d

Structure of glycan moieties responsible for the extended circulatory life time of fetal bovine serum acetylcholinesterase and equine serum butyrylcholinesterase.

Abstract: Cholinesterases are serine hydrolases that can potentially be used as pretreatment drugs for organophosphate toxicity, as drugs to alleviate succinylcholine-induced apnea, and as detoxification agents for environmental toxins such as heroin and cocaine. The successful application of serum-derived cholinesterases as bioscavengers stems from their relatively long residence time in the circulation. To better understand the relationship between carbohydrate structure and the stability of cholinesterases in circulation, we determined the monosaccharide composition, the distribution of various oligosaccharides, and the structure of the major asparagine-linked oligosaccharides units present in fetal bovine serum acetylcholinesterase and equine serum butyrylcholinesterase. Our findings indicate that 70-80% of the oligosaccharides in both enzymes are negatively charged. This finding together with the molar ratio of galactose to sialic acid clearly suggests that the beta-galactose residues are only partially capped with sialic acid, yet they displayed a long duration in circulation. The structures of the two major oligosaccharides from fetal bovine serum acetylcholinesterase and one major oligosaccharide from equine serum butyrylcholinesterase were determined. The three carbohydrate structures were of the biantennary complex type, but only the ones from fetal bovine serum acetylcholinesterase were fucosylated on the innermost N-acetylglucosamine residue of the core. Pharmacokinetic studies with native, desialylated, and deglycosylated forms of both enzymes indicate that the microheterogeneity in carbohydrate structure may be responsible, in part, for the multiphasic clearance of cholinesterases from the circulation of mice.
Get Full Text
Publication Date: 1997-06-17 PubMed ID: 9200697DOI: 10.1021/bi963156dGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explored the relationship between the carbohydrate structure and circulatory longevity of two types of cholinesterases. It found that most of the oligosaccharides in the enzymes are negatively charged and that the carbohydrate structure might partly account for how long these enzymes stay in the circulatory system.

Cholinesterases and Their Potential Uses

  • Cholinesterases, the subject of this study, are proteins classified as serine hydrolases.
  • They have potential use in medical and environmental applications: serving as preventive treatments for toxicity resulting from exposure to organophosphates, alleviating succinylcholine-induced apnea, or acting as detoxifying agents against environmental toxins such as heroin and cocaine.

Importance of Long Circulation Times

  • Cholinesterases derived from serum are particularly beneficial due to their extended life in the human circulation, which allows for longer periods of action and impact.
  • This research aimed to understand the biochemical reason for this longevity, particularly focusing on the relationship between the enzyme’s carbohydrate structure and its stability within the circulatory system.
  • To achieve this, the researchers identified the type and arrangement of monosaccharides and oligosaccharides in fetal bovine serum acetylcholinesterase (FBS AChE) and equine serum butyrylcholinesterase (Eq BChE).

Carbohydrate Structures in the Enzymes

  • Both FBS AChE and Eq BChE were found to contain predominantly negatively charged oligosaccharides, forming 70-80% of their carbohydrate structure.
  • The ratio of galactose to sialic acid showed that beta-galactose residues are only partially capped with sialic acid, though these enzymes still possess extended circulation times.
  • Detailed structures of main complex oligosaccharides from both enzymes were identified and mapped out. Those from FBS AChE were found to be fucosylated on the N-acetylglucosamine residue of the core, which wasn’t the case for Eq BChE.

Relevance of Findings

  • Tests with native, desialylated, and deglycosylated forms of both enzymes suggest that the variation (microheterogeneity) in the carbohydrate structures partly affect the rate at which the enzymes are cleared from the mice’s circulation.
  • The findings imply that the carbohydrate structure of the enzymes plays a crucial role in the extended circulatory longevity of cholinesterases and that alterations to these structures can impact their circulatory stability.

Cite This Article

APA
Saxena A, Raveh L, Ashani Y, Doctor BP. (1997). Structure of glycan moieties responsible for the extended circulatory life time of fetal bovine serum acetylcholinesterase and equine serum butyrylcholinesterase. Biochemistry, 36(24), 7481-7489. https://doi.org/10.1021/bi963156d

Publication

Biochemistry
ISSN: 0006-2960
NlmUniqueID: 0370623
Country: United States
Language: English
Volume: 36
Issue: 24
Pages: 7481-7489

Researcher Affiliations

Saxena, A
  • Division of Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Raveh, L
    Ashani, Y
      Doctor, B P

        MeSH Terms

        • Acetylcholinesterase / blood
        • Acetylcholinesterase / chemistry
        • Acetylcholinesterase / pharmacokinetics
        • Animals
        • Butyrylcholinesterase / blood
        • Butyrylcholinesterase / chemistry
        • Butyrylcholinesterase / pharmacokinetics
        • Carbohydrate Conformation
        • Carbohydrate Sequence
        • Carbohydrates / analysis
        • Cattle
        • Fetal Blood / enzymology
        • Glycosylation
        • Horses
        • Humans
        • Kinetics
        • Male
        • Mice
        • Mice, Inbred ICR
        • Molecular Sequence Data
        • Oligosaccharides / analysis
        • Oligosaccharides / chemistry
        • Polysaccharides / chemistry

        Citations

        This article has been cited 19 times.
        1. Aboulthana WM, Ibrahim NE, Osman NM, Seif MM, Hassan AK, Youssef AM, El-Feky AM, Madboli AA. Evaluation of the Biological Efficiency of Silver Nanoparticles Biosynthesized Using Croton tiglium L. Seeds Extract against Azoxymethane Induced Colon Cancer in Rats. Asian Pac J Cancer Prev 2020 May 1;21(5):1369-1389.
          doi: 10.31557/APJCP.2020.21.5.1369pubmed: 32458646google scholar: lookup
        2. El-Sayed AEB, Aboulthana WM, El-Feky AM, Ibrahim NE, Seif MM. Bio and phyto-chemical effect of Amphora coffeaeformis extract against hepatic injury induced by paracetamol in rats. Mol Biol Rep 2018 Dec;45(6):2007-2023.
          doi: 10.1007/s11033-018-4356-8pubmed: 30244397google scholar: lookup
        3. Engdahl C, Knutsson S, Fredriksson SÅ, Linusson A, Bucht G, Ekström F. Acetylcholinesterases from the Disease Vectors Aedes aegypti and Anopheles gambiae: Functional Characterization and Comparisons with Vertebrate Orthologues. PLoS One 2015;10(10):e0138598.
          doi: 10.1371/journal.pone.0138598pubmed: 26447952google scholar: lookup
        4. Lee J, Ballikaya S, Schönig K, Ball CR, Glimm H, Kopitz J, Gebert J. Transforming growth factor beta receptor 2 (TGFBR2) changes sialylation in the microsatellite unstable (MSI) Colorectal cancer cell line HCT116. PLoS One 2013;8(2):e57074.
          doi: 10.1371/journal.pone.0057074pubmed: 23468914google scholar: lookup
        5. Ilyushin DG, Smirnov IV, Belogurov AA Jr, Dyachenko IA, Zharmukhamedova TIu, Novozhilova TI, Bychikhin EA, Serebryakova MV, Kharybin ON, Murashev AN, Anikienko KA, Nikolaev EN, Ponomarenko NA, Genkin DD, Blackburn GM, Masson P, Gabibov AG. Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo. Proc Natl Acad Sci U S A 2013 Jan 22;110(4):1243-8.
          doi: 10.1073/pnas.1211118110pubmed: 23297221google scholar: lookup
        6. Biberoglu K, Schopfer LM, Tacal O, Lockridge O. The proline-rich tetramerization peptides in equine serum butyrylcholinesterase. FEBS J 2012 Oct;279(20):3844-58.
          doi: 10.1111/j.1742-4658.2012.08744.xpubmed: 22889087google scholar: lookup
        7. Solá RJ, Griebenow K. Glycosylation of therapeutic proteins: an effective strategy to optimize efficacy. BioDrugs 2010 Feb 1;24(1):9-21.
          doi: 10.2165/11530550-000000000-00000pubmed: 20055529google scholar: lookup
        8. Ngamelue MN, Homma K, Lockridge O, Asojo OA. Crystallization and X-ray structure of full-length recombinant human butyrylcholinesterase. Acta Crystallogr Sect F Struct Biol Cryst Commun 2007 Sep 1;63(Pt 9):723-7.
          doi: 10.1107/S1744309107037335pubmed: 17768338google scholar: lookup
        9. Lockridge O, Schopfer LM, Winger G, Woods JH. LARGE SCALE PURIFICATION OF BUTYRYLCHOLINESTERASE FROM HUMAN PLASMA SUITABLE FOR INJECTION INTO MONKEYS; A POTENTIAL NEW THERAPEUTIC FOR PROTECTION AGAINST COCAINE AND NERVE AGENT TOXICITY. J Med Chem Biol Radiol Def 2005 Jul 1;3:nihms5095.
          doi: 10.1901/jaba.2005.3-nihms5095pubmed: 16788731google scholar: lookup
        10. Gabel F, Weik M, Masson P, Renault F, Fournier D, Brochier L, Doctor BP, Saxena A, Silman I, Zaccai G. Effects of soman inhibition and of structural differences on cholinesterase molecular dynamics: a neutron scattering study. Biophys J 2005 Nov;89(5):3303-11.
          doi: 10.1529/biophysj.105.061028pubmed: 16100272google scholar: lookup
        11. Gabel F, Weik M, Doctor BP, Saxena A, Fournier D, Brochier L, Renault F, Masson P, Silman I, Zaccai G. The influence of solvent composition on global dynamics of human butyrylcholinesterase powders: a neutron-scattering study. Biophys J 2004 May;86(5):3152-65.
          doi: 10.1016/S0006-3495(04)74363-5pubmed: 15111428google scholar: lookup
        12. Cohen O, Kronman C, Velan B, Shafferman A. Amino acid domains control the circulatory residence time of primate acetylcholinesterases in rhesus macaques (Macaca mulatta). Biochem J 2004 Feb 15;378(Pt 1):117-28.
          doi: 10.1042/BJ20031305pubmed: 14575524google scholar: lookup
        13. Chitlaru T, Kronman C, Velan B, Shafferman A. Overloading and removal of N-glycosylation targets on human acetylcholinesterase: effects on glycan composition and circulatory residence time. Biochem J 2002 May 1;363(Pt 3):619-31.
          doi: 10.1042/0264-6021:3630619pubmed: 11964163google scholar: lookup
        14. Cohen O, Kronman C, Chitlaru T, Ordentlich A, Velan B, Shafferman A. Effect of chemical modification of recombinant human acetylcholinesterase by polyethylene glycol on its circulatory longevity. Biochem J 2001 Aug 1;357(Pt 3):795-802.
          doi: 10.1042/0264-6021:3570795pubmed: 11463350google scholar: lookup
        15. Chitlaru T, Kronman C, Velan B, Shafferman A. Effect of human acetylcholinesterase subunit assembly on its circulatory residence. Biochem J 2001 Mar 15;354(Pt 3):613-25.
          doi: 10.1042/0264-6021:3540613pubmed: 11237866google scholar: lookup
        16. Masson P, Cléry C, Guerra P, Redslob A, Albaret C, Fortier PL. Hydration change during the aging of phosphorylated human butyrylcholinesterase: importance of residues aspartate-70 and glutamate-197 in the water network as probed by hydrostatic and osmotic pressures. Biochem J 1999 Oct 15;343 Pt 2(Pt 2):361-9.
          pubmed: 10510301
        17. Chitlaru T, Kronman C, Zeevi M, Kam M, Harel A, Ordentlich A, Velan B, Shafferman A. Modulation of circulatory residence of recombinant acetylcholinesterase through biochemical or genetic manipulation of sialylation levels. Biochem J 1998 Dec 15;336 ( Pt 3)(Pt 3):647-58.
          doi: 10.1042/bj3360647pubmed: 9841877google scholar: lookup
        18. Mendelson I, Kronman C, Ariel N, Shafferman A, Velan B. Bovine acetylcholinesterase: cloning, expression and characterization. Biochem J 1998 Aug 15;334 ( Pt 1)(Pt 1):251-9.
          doi: 10.1042/bj3340251pubmed: 9693127google scholar: lookup
        19. Bekheit RA, Aboulthana WM, Serag WM. Assessment of the biological efficacy of gold Nannochloropsis oculata nano-extract against lithium-induced toxicity in rats. Sci Rep 2026 Jan 26;16(1):3269.
          doi: 10.1038/s41598-025-33835-5pubmed: 41588078google scholar: lookup
        Subscribe to our newsletter
        Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.