3 Benzyl-6-chloropyrone: a suicide inhibitor of cholesterol esterase
Conference
·
· Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6942976
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-
- Conference Information:
- Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
AMINO ACIDS
ATP
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CARBON 12
CARBON 14
CARBON ISOTOPES
CARBOXYLIC ACIDS
CATIONS
CHARGED PARTICLES
DRUGS
ENZYMES
ESCHERICHIA COLI
EVEN-EVEN NUCLEI
HYDROGEN ISOTOPES
IONS
ISOTOPE APPLICATIONS
ISOTOPE EFFECTS
ISOTOPE RATIO
ISOTOPES
KINETICS
LIGASES
LIGHT NUCLEI
LIPOTROPIC FACTORS
METHIONINE
MICROORGANISMS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
POTASSIUM COMPOUNDS
RADIOISOTOPES
REACTION KINETICS
STABLE ISOTOPES
TRACER TECHNIQUES
TRITIUM
VALENCE
YEARS LIVING RADIOISOTOPES
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
AMINO ACIDS
ATP
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CARBON 12
CARBON 14
CARBON ISOTOPES
CARBOXYLIC ACIDS
CATIONS
CHARGED PARTICLES
DRUGS
ENZYMES
ESCHERICHIA COLI
EVEN-EVEN NUCLEI
HYDROGEN ISOTOPES
IONS
ISOTOPE APPLICATIONS
ISOTOPE EFFECTS
ISOTOPE RATIO
ISOTOPES
KINETICS
LIGASES
LIGHT NUCLEI
LIPOTROPIC FACTORS
METHIONINE
MICROORGANISMS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
POTASSIUM COMPOUNDS
RADIOISOTOPES
REACTION KINETICS
STABLE ISOTOPES
TRACER TECHNIQUES
TRITIUM
VALENCE
YEARS LIVING RADIOISOTOPES