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Transcript
LIPOPROTEIN LIPASE
lipase = lipid hydrolyzing enzyme
lipoprotein = lipid and protein non-stoichiometric non-covalent aggregate
in blood, in lymph = chyle (and bile)
decreasing protein content (causing less density):
nascent HDL, HDL, LDL, IDL, VLDL, chylomicron (Chy)
High TAG containing lipoproteins: VLDL, Chy
Localization of lipoprotein lipase = LPL
anchored to the inner wall of capillaries and artheries to glucoseaminoglycans=
(GAG) = proteoglycans by ionic bonds
anchored to GAG to cells in interstitium
circulates in blood attached to lipoproteins
can be liberated by the addition of heparin
Place of synthesis
not the endothel, but the parenchymal cells:
adipocytes, myocytes, cardiocytes, macrophages, lung, spleen,
mammary gland, pancreas, placenta, smooth muscle,
steroid hormon producing glands
LPL is not found in adult liver. Instead of LPL there is hepatic lipase there,
anchored to sinusoids.
Homologues of lipase family:
lipoprotein lipase, hepatic lipase, pancreatic lipase, endothelial lipase.
All can hydrolyse TAG, their active site contains Ser, His,Asp.
Function of LPL
1.) Hydrolyzes sn-1 and sn-3 from TAG of VLDL and chylomicron. The produced
fatty acids and monoacyl-glycerol are
a.) absorbed to cells and take part in beta-oxidation yielding ATP
b.) absorbed to cells and TAG is resynthesized mainly in adipocytes and
lactating mammary gland
c.) FA are liberated, joined to albumin, FFA gives enegy for neighburing cells
(2.) Binds phospholipid surface of any of the lipoproteins and helps the uptake
of the whole particle (CR, IDL, LDL).
(3.) LPL is the ligand of different LP receptors, binds the LPs to cell surface, help
the uptake of the particle.
(4.) It helps the selective uptake of cholesterol ester from lipoproteins to cells,
including steroid hormon producing cells.
Structure and binding sites of LPL
It is a noncovalent homodimer. The monomer is unfunctional as hydrolase.
N
phospho active site
lipid-binding
lid
(Ser, His,
Asp)
C
GAG-binding
apo CIIsite
binding
(apo CII circulates
with VLDL, Chy)
Apoprotein CII activates LPL
to other monomer
LRP-binding
site
Regulation of synthesis is specific for tissues
The transcription, maturation, transport, activity are regulated by:
hormons: insulin, estragen, adrenalin, prolactin
metabolites: glucose, PUFA, cholesterol
cytokines: TNFα, IL, IF, PG
In lactating mammary gland it is continuously very active to produce milk
(milk production has priority over everything, in mild starvation as well).
In heart it is highly active ( and skeletal muscle) to yield energy especially in
starvation, lower activity of LPL in well fed.
In adipocytes it is induced and activated in well fed state (to put on weight) and
inhibited in fasting.
In bacterial infection it is inhibited in adipocytes to prevent FA uptake there.
Instead, TAG hydrolysis ensures energy for other tissues.
Signs of LPL deficiency
In blood the degradation of chylomicron and VLDL are very slow, causing
hyperchylomicronemia and hypertriglyceridemia (TAG >15 mM)
blood plasm is like a red milk or tomato sauce
Cholic abdominal pain (even after 1st suckling)
Fat deposits everywhere, macrophages phagositose chylomicrones to cause
hepatosplenomegaly, eruptive xanthomas, lipemia retinalis
Large chylomicrones plug the capillaries to prevent the traffic of materials,
including oxigen. It causes dyspnoe in lung, memory loss, dementia in
CNS, peripheral neuropathy.
pancreatitis
false laboratory values
dislike of fatty food, that caused symptoms
Therapy
avoidance of fatty food
small amount of essential fatty acid containing see food, plant oils are allowed
milk products are allowed (contain middle chain fatty acid absorbed from stomach)