The reliability of three popular semiempirical quantum chemical methods (AMI, PM3, MNDO) for the treatment of tautomeric equilibria is tested in a series of five-membered nitrogen heterocycles. The known flaw of M N D O to overestimate the stability of compounds with two or more adjacent pyridine-like lone pairs is also present in AMI and to a somewhat lesser extent in PM3. Tautomeric species d...

Reaction of tryptamine 1 with dimethyl -3-methoxyallylidenemalonate 2 afforded N?-[4,4-bis (methoxycarbonyl)-1,3-butadienyl] tryptamine 3 which in combination with acetylchloride and pyridine in dichloromethane gave N?, N?-[acetyl]-[(4,4-dinethoxycarbonyl) 1,3butadienyl] tryptamine 4. Treatment of 3 with sodium hydroxide afforded 2H[N-(3-indolyl) ethyl] 2-oxo-3-methoxycarbonyl-1-pyridine 5. Cy...

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine carcinogen prevalent in the human diet. To exert its mutagenic and carcinogenic effects, PhIP undergoes bioactivation to N-hydroxy-PhIP followed by O-esterification via cytosolic acetyltransferases or sulfotransferases to form DNA adducts. We investigated the role of cytosolic acetyltransferases and sulfotransferases...

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, E.C. 1.1.1.34), the major ratelimiting enzyme of the sterol biosynthetic pathway, was studied in ileal epithelial cells isolated in a villus-to-crypt gradient according to Weiser (Weiser, M. M. 1973.5. Bzol. Chem. 248: 2536-2541). Alkaline phosphatase (E.C. 3.1.3.1) served as a marker for the mature villus cells. Protease effec...

Deficiency of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, the rate-limiting enzyme in hepatic ketogenesis, causes potentially life-threatening hypoglycemic hypoketotic coma during fasting periods. In the normal, nonfasting state, patients are completely asymptomatic and show no abnormalities in standard metabolic tests. As a consequence, diagnosing 3-hydroxy-3-methylglutaryl-CoA synt...