Engineering of human cholinesterases explains and predicts diverse consequences of administration of various drugs and poisons.
Pharmacol Ther
; 67(2): 283-322, 1995.
Article
em En
| MEDLINE
| ID: mdl-7494866
ABSTRACT
The acetylcholine hydrolyzing enzyme, acetylcholinesterase, primarily functions in nerve conduction, yet it appears in several guises, due to tissue-specific expression, alternative mRNA splicing and variable aggregation modes. The closely related enzyme, butyrylcholinesterase, most likely serves as a scavenger of toxins to protect acetylcholine binding proteins. One or both of the cholinesterases probably also plays a non-catalytic role(s) as a surface element on cells to direct intercellular interactions. The two enzymes are subject to inhibition by a wide variety of synthetic (e.g., organophosphorus and carbamate insecticides) and natural (e.g., glycoalkaloids) anticholinesterases that can compromise these functions. Butyrylcholinesterase may function, as well, to degrade several drugs of interest, notably aspirin, cocaine and cocaine-like local anesthetics. The widespread occurrence of butyrylcholinesterase mutants with modified activity further complicates this picture, in ways that are only now being dissected through the use of site-directed mutagenesis and heterologous expression of recombinant cholinesterases.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organofosforados
/
Carbamatos
/
Regulação Enzimológica da Expressão Gênica
/
Inibidores da Colinesterase
/
Colinesterases
/
Inseticidas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Pharmacol Ther
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Israel