Detail of "2949-92-0"

Reference

Blockade of acetylcholine synthesis in organophosphate poisoning

Blockade of acetylcholine synthesis in organophosphate poisoning. Hopff, W. H.; Riggio, G.; Waser, P. G. (Pharmakol. Inst., Univ. Zurich, Zurich CH 8006, Switz.). Toxicol. 107-44-8 and 96-64-0 which are cas registry numbers are also used here. Appl. Pharmacol., 72(3), 513-18 (English) 1984. CODEN: TXAPA9. ISSN: 0041-008X. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) The time from sarin [107-44-8] (2 mg/kg) injection to death in rats (controls) was 2:59 min. With a Me methanethiosulfonate (MMTS) [2949-92-0] dosage of 133.5 mg/kg prior to sarin, it was prolonged to min. With the same dosage of MMTS under identical conditions, the time from soman [96-64-0] (2 mg/kg) injection to death was prolonged from 6:08 to min. Although MMTS, which blocks acetylcholine synthesis, cannot be used as a therapeutic agent, their attempt has demonstrated a utility in treating organophosphate poisoning in mice and rats and points in a direction where further work might be fruitful. .

Conformation-dependent inactivation of human betaine-homocysteine S-methyltransferase by hydrogen peroxide in vitro

Conformation-dependent inactivation of human betaine-homocysteine S-methyltransferase by hydrogen peroxide in vitro. Miller, Catherine M.; Szegedi, Sandra S.; Garrow, Timothy A. ( Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA). Biochemical Journal, 392(3), 443-448 (English) 2005 Portland Press Ltd. CODEN: BIJOAK. ISSN: 0264-6021.Some commonly used reagents like 2949-92-0 and 9029-78-1 are used in this experiment. DOCUMENT TYPE: Journal CA Section: 7 (Enzymes) Betaine-homocysteine S-methyltransferase (BHMT) transfers a Me group from betaine to homocysteine (Hcy) to form DMG (dimethylglycine) and Met. The reaction is ordered Bi Bi; Hcy is the first substrate to bind and Met is the last product off. Using intrinsic tryptophan fluorescence [Castro, Gratson, Evans, Jiracek, Collinsova, Ludwig and Garrow (2004) Biochem. 43, 5341-5351], it was shown that BHMT exists in three steady-state conformations: enzyme alone, enzyme plus occupancy at the first substrate-binding site (Hcy or Met), or enzyme plus occupancy at both substrate-binding sites (Hcy plus betaine, or Hcy plus DMG). Betaine or DMG alone do not bind to the enzyme, indicating that the conformational change assocd. with Hcy binding creates the betaine-binding site. CBHcy [S-(d-carboxybutyl)-D,L-homocysteine] is a bisubstrate analog that causes BHMT to adopt the same conformation as the ternary complexes. We report that BHMT is susceptible to conformation-dependent oxidative inactivation. Two oxidants, MMTS (Me methanethiosulfonate) and hydrogen peroxide (H2O2), cause a loss of the enzyme's catalytic Zn (Zn2+ ion) and a correlative loss of activity. Addn. of 2-mercaptoethanol and exogenous Zn after MMTS treatment restores activity, but oxidn. due to H2O2 is irreversible. CD and glutaraldehyde crosslinking indicate that H2O2 treatment causes small perturbations in secondary structure but no change in quaternary structure. Oxidn. is attenuated when both binding sites are occupied by CBHcy, but Met alone has no effect. Partial digestion of ligand-free BHMT with trypsin produces two large peptides, excising a seven-residue peptide within loop L2. CBHcy but not Met binding slows down proteolysis by trypsin. These findings suggest that L2 is involved in the conformational change assocd. with occupancy at the betaine-binding site and that this conformational change and/or occupancy at both ligand-binding sites protect the enzyme from oxidative inactivation. .