FAST MOVING FRONTS
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Scott W. Altmann talks with
ScienceWatch.com and answers a few questions about
this month's Fast Moving Front in the field of Pharmacology
& Toxicology. The author has also sent along images of
their work.
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Article: Niemann-Pick C1 like 1 protein is critical
for intestinal cholesterol absorption
Authors:
Altmann,
SW, et al.
SCIENCE, 303 (5661): 1201-1204 FEB 20 2004
Addresses: Schering Plough Corp, Res Inst, Dept Cardiovasc
Endocrine Res, 2015 Galloping Hill Rd, Kenilworth, NJ 07033
USA.
Schering Plough Corp, Res Inst, Dept Cardiovasc Endocrine
Res, Kenilworth, NJ 07033 USA.
Schering Plough Corp, Res Inst, Dept Discovery Technol,
Kenilworth, NJ 07033 USA.
(addresses may have been truncated)
Return to interview.
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Figures and descriptions:
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Figure
1:
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Figure 1: The small intestine is the organ
primarily responsible for the absorption of
dietary nutrients including cholesterol.
The enterocyte is the specialized cell that
mediates the intestinal absorption process
and provides the epithelial barrier between
the intestinal lumen and the circulatory
system (lymph). This illustration depicts
the step-wise progression of cholesterol
absorption and includes several known
enzymes and key molecules involved. The
identification of Niemann-Pick C1 like-1
(NPC1L1) enables the detailed understanding
of the initial cellular event of sterol
uptake, a process that also requires the
sterol efflux activity of the heterodimeric
ATP-binding cassette transporters G5 and G8
(ABCG5/8) to control sterol selectivity.
Once absorbed by the enterocyte,
cholesterol is reassembled into the
apolipoprotein B-48 (Apo B-48) containing
intestinal lipoprotein particle called a
chylomicron which is subsequently secreted
into the lymphatics and circulated to the
liver. Acyl CoA:cholesterol acyltransferase
(ACAT) converts free cholesterol (C) to
cholesterol ester (CE) by attaching a fatty
acid (FA) and microsomal triglyceride
transfer protein (MTP) loads the CE and
triglycerides (TG) into the chylomicron.
Inhibition of NPC1L1-mediated cholesterol
absorption by the drug ezetimibe reduces
plasma low-density lipoprotein-cholesterol
(LDL-C) levels.
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Figure
2:
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Figure 2: The Discovery
Team -
(Front Left) Nicholas J. Murgolo, Ph.D.
Research Fellow Discovery Technologies
(Front Right) Scott W. Altmann, Ph.D.
Principal Scientist Discovery
Technologies
(Back Left) Michael P. Graziano, Ph.D.
Executive Director Cardiovascular/
Metabolic Disease
(Back Right) Harry R. Davis Jr., Ph.D.
Distinguished Research Fellow
Cardiovascular/ Metabolic Disease
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2008 : March 2008 - Fast Moving Fronts : Scott W. Altmann - Figures & Descriptions
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