Amphetamine example1/7/2024 ![]() Full conversion was not attempted however, 12% conversion was achieved after 24 h and ( R) -amine was made (99.67% ee in organic layer, 99.99% ee in aqueous layer).ĪADHs catalyse the NAD(P)H dependent formation of amino acids from keto acids in the presence of ammonia. All reactions were stopped by adding methanol and analyzed by HPLC to detect amine peaks, except the adamantyl methyl ketone was analyzed by GC due to absorbance issues. 1 mM NADH/NAD + was added to the reactions. Twice as much regeneration enzyme activity ( Cb-FDH, Bs-GDH) was added to ensure that the reversible reaction would not occur and that enough co-substrate NADH was always present during the reaction. The aqueous reaction medium was 5 M NH 4Cl/OH pH 9.6 and the reaction was performed at 50☌. 0.25 mg of cFL1-AmDH was added to the reactions involving acetophenone and 1-adamantyl methyl ketone. ![]() The aqueous reaction medium was 5 M NH 4HCO 2/OH pH 9.6 and the reaction was performed at 35☌. ) was added for the pFPA and 3-methyl-1-phenyl-2-butanone reactions, respectively. 0.1 mg and 0.25 mg of F-AmDH (prepared as described in Ref. A phase ratio of 1:4 organic solvent heptane to aqueous is used for all reactions. To the reaction, 150 mM of substrate was added. Biphasic system reaction involving F-AmDH and pFPA. Therefore, there are the enantiomer-enantiomer interactions between S- and R-propranolol in glucuronidation. The CL int ratios of S-enantiomer to R-enantiomer are 3.8 times and 6.5 times for racemic propranolol and individual enantiomers, respectively. The mechanism of enantioselective excretion of propranolol enantiomers is that UGT1A9 prefers catalyzing S-enantiomer to form S-propranolol glucuronide. The results showed the elimination rate constant k of S-propranolol glucuronide was less than that of R-propranolol glucuronide and the elimination half-life (t 1/2), T max and the cumulative excretion amount (X u0–24) of R-propranolol glucuronide were significantly less than that of S-propranolol glucuronide. It was reported that the propranolol glucuronidation of the side chain undergoes stereoselective excretion in 16 adult Chinese Han volunteers in urine after an oral administration of 20-mg racemic propranolol. And it can be speculated that this phenomenon may come from the stereoselective characteristic during the process of MA conversion to AMP, causing the lack of R-MA converting to R-AMP and R-pOH-MA. The drug enzyme CYP2D6, which mediates this transformation, has a better affinity to the S-enantiomer of the analog of MA, MDMA. The urinary excretion of S-pOH-MA was slightly higher than that of R-pOH-MA. The formation of S-AMP (7%) was approximately three times larger than that of R-AMP (2%), and the excretion of S-MA (42%) was lower than that of R-MA (52%). The formation and elimination of the metabolites of methamphetamine (MA), amphetamine (AMP), and p-hydroxymethyl amphetamine (pOH-MA) showed significant enantioselectivity. And there are various reason accounting for the drug stereoselective excretion. Except for glomerular filtration, the active secretion of the renal tubules, the active and passive reabsorption processes all show stereoselectivity, which makes the renal clearance rate of certain drugs present a certain level of stereoselectivity. The kidney is the main organ for drug excretion. Lushan Yu, Su Zeng, in Identification and Quantification of Drugs, Metabolites, Drug Metabolizing Enzymes, and Transporters (Second Edition), 2020 4.4 Stereoselectivity of chiral drug excretion
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