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LIPOPROTEIN LIPASE

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)

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LIPOPROTEIN LIPASE

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  1. LIPOPROTEIN LIPASE

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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)

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