LIPOPROTEIN LIPASE

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LIPOPROTEIN LIPASE
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• 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

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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.
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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.
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Structure and binding sites of LPL It is a
noncovalent homodimer. The monomer is
unfunctional as hydrolase.
N
C
phospho active site GAG-binding to other
monomer lipid-binding apo CII- site LRP-binding
lid (Ser, His, binding site
Asp) (apo CII circulates with VLDL,
Chy) Apoprotein CII activates LPL
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• 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 TNFa, 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.

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• Signs of LPL deficiency
• In blood the degradation of chylomicron and VLDL
  are very slow, causing hyperchylomicronemia and
  hypertriglyceridemia (TAG gt15 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)