Molecular and cellular biology of cholinesterases

Massoulié, Jean; Pezzementi, Leo; Bon, Suzanne; Krejci, Éric; Vallette, François M.

doi:10.1016/0301-0082(93)90040-y

Cited by 1,151 publications

(822 citation statements)

References 403 publications

Supporting

Mentioning

785

Contrasting

Unclassified

Order By: Relevance

“…Prospects & Overviews ... and insecticides [22], the synthesis and structural properties of ACHe have received considerable attention [23][24][25]. Salpeter and coworkers [26,27] and Rosenberry and coworkers [28,29] have carried out detailed studies of the kinetics of ACH release, binding to post-synaptic receptors, and degradation by ACHe.…”

Section: C Reed Et Almentioning

confidence: 99%

The biological significance of substrate inhibition: A mechanism with diverse functions

2010

View full text Add to dashboard Cite

Many enzymes are inhibited by their own substrates, leading to velocity curves that rise to a maximum and then descend as the substrate concentration increases. Substrate inhibition is often regarded as a biochemical oddity and experimental annoyance. We show, using several case studies, that substrate inhibition often has important biological functions. In each case we discuss, the biological significance is different. Substrate inhibition of tyrosine hydroxylase results in a steady synthesis of dopamine despite large fluctuations in tyrosine due to meals. Substrate inhibition of acetylcholinesterase enhances the neural signal and allows rapid signal termination. Substrate inhibition of phosphofructokinase ensures that resources are not devoted to manufacturing ATP when it is plentiful. In folate metabolism, substrate inhibition maintains reactions rates in the face of substantial folate deprivation. Substrate inhibition of DNA methyltransferase serves to faithfully copy DNA methylation patterns when cells divide while preventing de novo methylation of methyl-free promoter regions. Keywords:.b iological function; enzyme kinetics; substrate inhibitionThe kinetics of an enzymatic reaction are typically studied by varying the concentration of substrate and plotting the rate of product formation as a function of substrate concentration. In the conventional case this yields a typical hyperbolic Michaelis-Menten curve, and a linear reciprocal LineweaverBurk plot, from which the kinetic constants of the enzyme can be calculated. A surprisingly large number of enzymes do not behave in this conventional way. Instead, their velocity curves rise to a maximum and then decline as the substrate concentration goes up. This phenomenon is referred to as substrate inhibition, and it is estimated that it occurs in some 20% of enzymes [1]. A partial list of enzymes that show substrate inhibition appears in Box 1.Substrate inhibition is often interpreted as an abnormality that comes from using artificially high substrate concentration in a laboratory setting. In a review article on the mechanisms of substrate inhibition in 1994, Kuehl [2] commented that ''although recognized early on as an almost universal phenomenon, it has nevertheless met an almost universal disinterest. Probably the main reason for this neglect is that the majority of enzymologists and many authorities in the field regard substrate inhibition as being almost always a nonphysiological phenomenon.'' There are several reasons for suspecting that substrate inhibition is not a pathological phenomenon, but a biologically relevant regulatory mechanism. First, in many cases normal substrate concentrations are to the right of the velocity maximum, which indicates that these enzymes typically operate under substrate inhibition. Second, many enzymes have specialized sites where a second substrate molecule can bind and act as an allosteric inhibitor. For those enzymes, substrate inhibition is clearly a specially evolved property. Third, evidence is accumulating that substr...

show abstract

Section: C Reed Et Almentioning

confidence: 99%

The biological significance of substrate inhibition: A mechanism with diverse functions

2010

View full text Add to dashboard Cite

show abstract

“…Enzyme cholinesterase is present in all mammals and two classes have been identified as acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (non-specific, pseudocholinesterase, BChE; EC 3.1.1.8) in serum. AChE exists in the central nervous system, platelets and the erythrocyte membrane while BChE is more abundant in the serum and it is synthesized by the liver and secreted into the circulation [4]. BChE is also found in adipose tissue, the small intestine, and smooth muscle cells [5].…”

Section: Introductionmentioning

confidence: 99%

Abdominal Obesity Associated with Elevated Serum Butyrylcholinesterase Activity, Insulin Resistance and Reduced High Density Lipoprotein-Cholesterol Levels

et al. 2014

View full text Add to dashboard Cite

Abdominal obesity (AO) has a strong correlation with cardiovascular disease and has been linked to Alzheimer's disease and type 2 diabetes. We investigated the association between AO and elevated serum butyrylcholinesterase (BChE) activity, insulin resistance and the serum lipid profile, including triglyceride (TG), HDLcholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels in AO and non-AO women subjects. A total of 500 AO subjects (age 49.1 ± 10.5 years), and 142 non-AO women subjects (age 49.9 ± 11.9 years) were enrolled for the general biochemistry tests, serum BChE, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Body mass index, waist circumference, Blood pressure (BP), plasma glucose (Glu), triglyceride (TG), BChE, insulin, HOMA-IR were significantly higher and HDL-C levels were significantly lower in AO subjects (p \ 0.05). Waist circumference was significantly correlated with BP, Glu, TG, BChE, insulin and HOMA-IR in AO subjects. Multiple logistic regression demonstrated that AO was associated with elevated BChE, HOMA-IR, hypertension and reduced HDL-C after adjusting for these variables. AO is associated with elevated BChE, insulin resistance, HT and reduced HDL-C. These may predict the development of type 2 diabetes mellitus and may be associated with cognitive disorder in the future, both are mediated through insulin resistance.

show abstract

“…The predominant monomeric and dimeric forms of native AChE contain a hydrophobic domain at their carboxyl-terminus, either as an attached glycophospholipid or an amphipathic sequence (Massoulie et al, 1993), both being likely to limit the propensity for crystallization. In the dimeric Torpedo AChE, the diglyceride on the glycophospholipid, which serves as the hydrophobic anchor in the membrane, was enzymatically cleaved prior to crystallization (Sussman et al, 1988).…”

mentioning

confidence: 99%

Soluble monomeric acetylcholinesterase from mouse: Expression, purification, and crystallization in complex with fasciculin

Marchot

Ravelli²,

Raves

et al. 1996

Protein Science

View full text Add to dashboard Cite

A soluble, monomeric form of acetylcholinesterase from mouse (mAChE), truncated at its carboxyl-terminal end, was generated from a cDNA encoding the glycophospholipid-linked form of the mouse enzyme by insertion of an early stop codon at position 549. Insertion of the cDNA behind a cytomegalovirus promoter and selection by aminoglycoside resistance in transfected HEK cells yielded clones secreting large quantities of mAChE into the medium. The enzyme sediments as a soluble monomer at 4.8 S. High levels of expression coupled with a one-step purification by affinity chromatography have allowed us to undertake a crystallographic study of the fasciculinmAChE complex. Complexes of two distinct fasciculins, Fasl-mAChE and Fas2-mAChE, were formed prior to the crystallization and were characterized thoroughly. Single hexagonal crystals, up to 0.6 mm x 0.5 mm x 0.5 mm, grew spontaneously from ammonium sulfate solutions buffered in the pH 7.0 range. They were found by electrophoretic migration to consist entirely of the complex and diffracted to 2.8 A resolution. Analysis of initial X-ray data collected on Fas2-mAChE crystals identified the space group as P6,22 or P6,22 with unit cell dimensions a = b = 75.5 A, c = 556 A, giving a V,, value of 3.1 A3/Da (or 60% of solvent), consistent with a single molecule of FasZAChE complex (72 kDa) per asymmetric unit. The complex Fasl-mAChE crystallizes in the same space group with identical cell dimensions.

show abstract

Molecular and cellular biology of cholinesterases

Cited by 1,151 publications

References 403 publications

The biological significance of substrate inhibition: A mechanism with diverse functions

The biological significance of substrate inhibition: A mechanism with diverse functions

Abdominal Obesity Associated with Elevated Serum Butyrylcholinesterase Activity, Insulin Resistance and Reduced High Density Lipoprotein-Cholesterol Levels

Soluble monomeric acetylcholinesterase from mouse: Expression, purification, and crystallization in complex with fasciculin

Contact Info

Product

Resources

About