An explanation for the different inhibitory characteristics of human serum butyrylcholinesterase phenotypes deriving from inhibition of atypical heterozygotes.
The time course of inhibition of butyrylcholinesterase (EC 3.1.1.8) by the dimethylcarbamate Ro 02-0683 in sera taken from patients heterozygous for the usual (U), atypical (A), K or J variants was followed using propionylthiocholine as substrate. Data obtained were used to determine rate constants of inhibition together with the contribution made by each variant to total enzyme activity. The findings substantiate earlier reports that J and K mutations lead to quantitative changes in the concentration of usual enzyme in contrast to the qualitative changes of the atypical variant. The contribution of the atypical enzyme to the total activity in serum from UA, AK and AJ heterozygotes was respectively 17-20, 24-31 and 34-53%. The altered ratios of atypical to usual, K or J enzyme in UA, AK and AJ together with the constants on the usual enzyme alone, explain the differences in observed inhibitor numbers which enable these heterozygotes to be identified.
Institute for Medical Research and Occupational Health, Zagreb, Croatia. vesimeon@mimi.imi.hr
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Simeon-Rudolf
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Kovarik
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Skrinjarić-Spoljar
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Evans
D001049:Apnea / Q000139:chemically induced / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000097:blood* / Q000235:genetics*; D002219:Carbamates / Q000493:pharmacokinetics / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D003992:Dibucaine / Q000493:pharmacokinetics / Q000494:pharmacology; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D007700:Kinetics; D009467:Neuromuscular Depolarizing Agents / Q000009:adverse effects / Q000627:therapeutic use; D010641:Phenotype; D000644:Quaternary Ammonium Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D012969:Sodium Fluoride / Q000493:pharmacokinetics / Q000494:pharmacology; D013390:Succinylcholine / Q000009:adverse effects / Q000627:therapeutic use; D013860:Thiocholine / Q000031:analogs & derivatives / Q000378:metabolism
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D009467:Neuromuscular Depolarizing Agents; D000644:Quaternary Ammonium Compounds; C006266:Ro 20683; C009063:propionylthiocholine; D013860:Thiocholine; D012969:Sodium Fluoride; D002091:Butyrylcholinesterase; D013390:Succinylcholine; D003992:Dibucaine