Cholinesterase hydrolysis and substrate inhibition of lactoylcholines

Stereoisomeric lactoyl-.beta.-methylcholine iodides. Interaction with cholinesterase and acetylcholinesterase

“…Preparation of (±)-Lactoyl-d-methylcholine Iodide (mp 125-126°). This compound was prepared according to the method of Sastry.3 The product was fractionally recrystallized from ethanol and gave a fraction with mp 125-126°(lit.3 mp 122.8-124.4°); nmr (D20) two doublets centered at 6 1.90 and 1.97 (=7=6 Hz,6 H, ß-CHs and acyl CH3), 3.76 [s, 9 H, +N(CH3)3], 4.0-4.6 (m, 3 H, <*-CH2, 0-methine proton), 5.02 (q, 1 H, lactate methine proton). Examination of the mother liquors gave fractions with mp 95-103°.…”

“…This compound was prepared as reported for o-O-acetyllactoyl-L-d-methylcholine iodide but using racemic reagents. Fractional crystallization of product from ethanol gave a fraction, mp 141-142°, as the least soluble fraction: nmr (D20) two doublets centered at 1.79 and 1.94 (=7=6 Hz, 6 H, d-CH3 and acyl CH3), 2.6 (s, 3 H, CH3CO), 3.62 [s, 9 H, +N(CH3)3], 5.60 (q, 1 H, lactate methine) .Anal. (ChH2204NI) C, H.…”

“…It can be seen therefore that the configuration of the acyl moiety has little significant effect upon the various stages in the reaction sequence, in agreement with previous studies using the enantiomers of lactoylcholine iodide. 6 It is interesting to note that, although cholinesterase does not hydrolyze acetyl-d-methylcholine, increasing the length of the acyl group leads to stereospecific enzyme-catalyzed hydrolysis, e.g., L-butyryl-/3-methylcholine is hydrolyzed by the enzyme. 17 The results obtained using the stereoisomeric lactoyl-d-methylcholines further confirm the stereospecificity of cholinesterase toward the l configuration of d-methylcholine esters and would suggest that the inability of cholinesterase to hydrolyze acetyl-d-methylcholine is the results of a poor affinity of the compound for the enzyme active site.…”