Title: Molecular basis of succinylcholine sensitivity in a prairie Hutterite kindred and genetic characterization of the region containing the BCHE gene Zelinski T, Coghlan G, Mauthe J, Triggs-Raine B Ref: Mol Genet Metab, 90:210, 2007 : PubMed
The tetrameric glycoprotein butyrylcholinesterase (BChE; EC 3.1.1.8) is one of two enzymes that hydrolyze choline esters. The controlling gene (BCHE) is comprised of four coding exons and is located on chromosome 3q26. Based on BChE activity measurements in the presence and absence of dibucaine, usual (designated U) and atypical (designated A) gene products have been distinguished. Homozygotes for the A gene product are at risk for prolonged apnea following exposure to the surgical anesthetics succinylcholine or mivacurium. In this report, we detail biochemical and molecular investigations of succinylcholine sensitivity in a prairie Hutterite kindred. Our results establish that BChE activities in the family members are impacted by two distinct BCHE mutations, namely, c.209A>G p. D70G and c.1615G>A p. A539T. However, homozygotes for the c.209A>G mutation (i.e., atypical or A) are the only individuals whose BChE activity could lead to adverse reactions to succinylcholine. Interestingly, haplotype analysis of the chromosomal region containing BCHE indicates that the c.209A>G mutation is carried on a unique haplotype, suggesting that it was likely introduced into the population only once. Conversely, the c.1615G>A mutation is carried on various haplotypes and was likely introduced into the population more than once.
Title: Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene accounts for YT blood group polymorphism Bartels CF, Zelinski T, Lockridge O Ref: American Journal of Human Genetics, 52:928, 1993 : PubMed
Acetylcholinesterase is present in innervated tissues, where its function is to terminate nerve impulse transmission. It is also found in the red blood cell membrane, where its function is unknown. We report the first genetic variant of human acetylcholinesterase and support the identity of acetylcholinesterase as the YT blood group antigen. DNA sequencing shows that the wild-type sequence of acetylcholinesterase with His322 (CAC) is the YT1 blood group antigen and that the rare variant of acetylcholinesterase with Asn322 (AAC) is the YT2 blood group antigen. Two additional point mutations in the acetylcholinesterase gene do not affect the amino acid sequence of the mature enzyme.
Title: Mode of action of herbicidal ALS-inhibitors on acetolactate synthase from green plant cell cultures, yeast, and Escherichia coli Babczinski P, Zelinski T Ref: Pest Sci, 31:305, 1991 : PubMed
Inhibitors of branched-chain amino acid biosynthesisby inhibiting acetolactate synthase (ALS)represent the most active group of herbicidal compounds to date (Shaner, D.L., Recent Adv. Phytochem. 23 (1989) 227-61). A microbial screening technique has been developed to investigate known and possible new ALS-inhibitors. Escherichia coli mutant FD 1062, which expresses only valine-resistant ALS II isoenzyme as the solely branched-chain amino acid synthesizing isoenzyme, has been used extensively to optimize known and to screen for new chemical classes of ALS-inhibitors, respectively. Herbicidal compounds like sulfonylureas, triazolopyrimidines, pyrimidylsalicylates, carbamoylpyrazolines, sulfonylimino-azinyl-heteroazoles, sulfonylamide azines, and substituted sulfonyldiamides, respectively, are active on minimal medium with Ki-values which resemble the rank order of biological activity of these compounds in the greenhouse. Interestingly, herbicidal imidazolinones are not at all inhibitory on E.coli strain FD 1062 in vivo although, of course, they exert high activity on isolated bacterial ALS. Similarly, N-protected valylanilides, pyrimidyl mandelic acids, benzenesulfonyl carboxamides, and uhiquinone-O are inactive in the bacterial assay but have been shown by other methods to act as ALS inhibitors. Additionally, reversal experiments can he performed to exclude, e.g. artificial inhibitory effects of test compounds. Moreover, a thin-layer biogram application technique opens the opportunity to test mixtures of chemicals.
From green plant cell cultures (Catharanthus roseus) ALS has been isolated and characterized in terms of inhibition by sulfonylureas, imidazolonones, triazolopyrmidines, salicylated, and carbamoylpyrazolines, imidazolinones, triaiolopyritnidines, salicydates, and carbarnoyl-razolines, respectively. All five types show biphasic slow tight binding kinetics with Stedy state I50 values of 0.5 nm (sulforneturon), 1.9 nm (triazolopjirimidine), 8.3 nm (salicylate), 23 nm (imazapyr), and 135 nm (carbamoylpyrazoline),respectively .
Isolated ALS from Saccharomyces cerevisiae is equallv well blocked by herbicidal ALS inhibitors although with different I50values ( triazoiopyrimidine, 21 nm, sulforneturon, 70 nm, salicylate, 21 um, imaiapyr, 38 um, and carbamoylpyrazoline, 148 um ). Surprisingly, biphasic kinetics could not be observed with the yeast enzjtme although slow binding hehauiour was clearly established.
The antithetical antigens YT1 and YT2 constitute the YT blood group system (International Society of Blood Transfusion system number 11). Despite being serologically well defined, the YT blood group locus (YT) has not secured a chromosomal location. In our report, peak lods of 3.61 at theta = 0.00 for YT:COL1A2 and of 3.31 at theta = 0.00 for YT:D7S13 allow us to assign YT to the long arm of chromosome 7.
