3 Benzyl-6-chloropyrone: a suicide inhibitor of cholesterol esterase

Conference · Thu May 01 00:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6942976

Saint, C; Gallo, I; Kantorow, M; Bailey, J M

Cholesterol, absorbed from the intestine, appears in lymph as the ester. Cholesterol esterase is essential for this process, since depletion of the enzyme blocks and repletion restores, absorption. Selective inhibitors of cholesterol esterase may thus prove useful in reducing cholesterol uptake. A series of potential suicide substrates were synthesized which, following cleavage by the enzyme, would attack the putative nucleophile in the active site. One of these, 3-benzyl-6-chloropyrone (3BCP), inhibited both synthesis and hydrolysis of /sup 14/C-cholesteryl oleate with an I/sub 50/ of approximately 150 ..mu..M. The inactivation was time-dependent and characteristic of a suicide mechanism. The ..cap alpha.. pyrone structure (lactone analog) is cleaved by a serine-hydroxyl in the active site. This generates an enoyl chloride which inactivates the imidazole believed to play a part in the catalytic function of the enzyme. Inhibition by 3BCP is selective for cholesterol esterase. The activity of pancreatic lipase as not affected by concentrations up to 1 mM.

• OSTI ID: 6942976
• Report Number(s): CONF-8606151-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARBON 14
ISOTOPE RATIO
LIGASES
BIOCHEMICAL REACTION KINETICS
ISOTOPE EFFECTS
TRITIUM
ATP
CARBON 12
CATIONS
ESCHERICHIA COLI
METHIONINE
POTASSIUM COMPOUNDS
TRACER TECHNIQUES
VALENCE
ALKALI METAL COMPOUNDS
AMINO ACIDS
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBON ISOTOPES
CARBOXYLIC ACIDS
CHARGED PARTICLES
DRUGS
ENZYMES
EVEN-EVEN NUCLEI
HYDROGEN ISOTOPES
IONS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
LIPOTROPIC FACTORS
MICROORGANISMS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIOISOTOPES
REACTION KINETICS
STABLE ISOTOPES
YEARS LIVING RADIOISOTOPES
550201* - Biochemistry- Tracer Techniques