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.
Publication Date: 1997-06-17 PubMed ID: 9200697DOI: 10.1021/bi963156dGoogle Scholar: Lookup
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- Journal Article
Summary
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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
Researcher Affiliations
- Division of Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
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
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- 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.
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- 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.
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