Common medical problems

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Common medical problems
Presented by Alastair Dearie
Familial ligand-defective apoB
From American Scientist, Sept.-Oct. 1995.
False-color scanning electron micrograph of a
healthy artery. http//www.aoe.vt.edu/jschetz/flu
idnature/unit07/unit7a.html
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Excess carbohydrate and fat is converted into
triacylglycerols by the liver these plus dietary
triacylglycerols and cholesterol are solubilized
in lipid protein complexs. The triacylglycerol
lipid droplets and other substances are
surrounded by polar phospholipids and proteins
called apolipoproteins.
LDL (low density lipoproteins) are the main
plasma carriers of cholesterol for delivery to
all tissues
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The main apolipoprotein of LDLs is apoB-100

• apoB-100 is secreted from the liver

• LDLs are taken into cells by LDL
  receptor-mediated endocytosis.

• Interaction between the LDL and LDL receptors in
  the cell membrane requires the presence of
  apoB-100. (apoB-100 is the ligand for the
  receptor)

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LDL receptor-mediated endocytosis
LDL receptor
ApoB-100
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(Better diagram)
http//www.iemrams.spb.ru8100/english/molgen/fh-e
n/cell-path.htm
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Familial ligand-defective apoB is a specific
genetic defect leading to familial
hypercholesterolaemia and atherosclerosis.
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Receptor binding requires a specific conformation
Involving interaction between Arginine 3500 and
Tryptophan 4369 in the carboxyl tail of the
apoB-100 protein
Glutamine
Tryptophan
Most common mutation G9775 --gt A found in Europe
and North America
Another mutation is C9774 --gt T first found in
the scottish population and is present in Familal
apoB of Asian descent.
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This delays the uptake of LDLs from the plasma
into cells leading to hypercholesterolaemia. The
uptake VLDL and other lipoproteins is uneffected.

• The levels of LDLs in the blood increase leading
  to an increase in nonhepatic cells uptake of LDLs
  without LDL receptors. This allows up take by
  monocytes and macrophages, leading to plaque
  depositation in the coronary arteries

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Frequency1/500-1/700 of caucasians in Europe
and North America.Fifteen percent of familial
hypercholesterolaemia is due to ligand-defective
apoB-100. Heterozygous carriers of an apoB
mutation have an increased risk for coronary
artery disease 40 in males and 20 in females
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Questions?(I wont be able to answer them but
have a go any way.)
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http//www.dentistry.leeds.ac.uk/biochem/thcme/lip
oproteins.htmlhttp//www.thefutureforum.com/polym
orph/intestine_apolipoprotein_b.asphttp//www.eme
dicine.com/med/topic1072.htmhttp//www.iemrams.sp
b.ru8100/english/molgen/fh-en/ldl-rec.htmwww.t
hirdway-site.co.uk
References!
http//www.soundandvisionmag.com/idealbb/view.asp?
topicID34290pageNo1num20