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Metabolism of lipoproteins & its disorders(Chylomicron & VLDL & LDL).pptx
- 1. Transportation of Lipids /Metabolism of lipoproteins
- 2. Exogenous pathway eg: Metabolismof Chylomicrons & Endogenous pathways -Metabolism of VLDL, LDL& - reverse cholesterol transportation: HDL
- 3. Chylomicrons Density (g/mL) Protein % CH % TG % PL % Apo proteins Site of syn Functions < 0.952 4 85 9 Apo-A, B48, C & E Intestine Transport of dietary TGs and cholesterol esters from intestine to peripheral tissues and liver.
- 4. Chylomicron metabolism Carry dietaryTG, Ch & chE to the peripheral tissues. C-II & PL + A-II & C-III - -E Thoracic duct Some of the PL LDL receptor protein (LPL)
- 5. Endogenous pathways Very lowdensity lipoproteins (VLDL ) / IDL Density (g/mL) Protein % CH % TG % PL % Apo proteins Site of syn Functions 0.95 – 1.006 10 15 55 20 Apo-B100, C &E Liver Transports endogenous TGs from liver to peripheral tissues.
- 6. Transport endogenous Triglycerides,Cholesterol from liver to the peripheral tissues. Half life is 1 -3hrs Cholesterol Ester Transfer Protein - CETP Transfer of CE and TG b/w HDL & VLDL & LDL TG
- 7. Low Density lipoprotein(LDL) Density (g/mL) Protein % CH % CE % TG % PL % Apo proteins Site of syn Functions 1.006- 1.063 20 10 40 8 22 Apo- B100 Plasma VLDL Transports cholesterol from liver to peripheral tissues. 50%
- 8.
- 9. Tissue uptake ofLDL LDL loaded with Cholesterol is taken up by peripheral tissues by 1. LDL receptors mediated endocytosis 2. Scavenger receptors (macrophages derived from monocytes) mechanisms Clathrin Maintain their cell membrane (All tissues) Steroid hormone synthesis (adrenal cortex) Bile acids synthesis (hepatocytes)
- 10. Transport Cholesterol fromliver to the peripheral tissues. Receptors mediated endocytosis
- 11. Scavenger receptors /Receptor independent mechanism Phagocytic macrophages (monocytes ) • It recognize LDL that has been modified – oxidized LDL • Uptake of oxidized LDL by macrophages in the arterial wall is potentially dangerous • Macrophages overloaded with CE are called foam cells
- 12. Lipoprotein(a) not apoprotein-A •Lp(a) is a LDLvariant containing a protein- apolipoprotein(a). • It is attached to apo-B100 of LDL by a disulfide bond • It is highly atherogenic & impairs fibrinolysis • It is an important marker of CHD
- 13. Endogenous pathway Metabolism ofHigh-Density Lipoproteins (HDL) / Reverse cholesterol transport
- 14. Density (g/mL) P % C % CE % TG % PL % Apo proteins Site of syn Functions 1.063- 1.210 40 223 5 30 Apo-A, C-II & E Liver & Intestine 1) Transports cholesterol from peripheral tissues to liver. 2) Serves as a circulating reservoir of Apo C-II & E 3) Transfers cholesteryl esters to VLDL & LDL in exchange for TG & PL from these particles High-Density Lipoprotein (HDL) 25%
- 15. Enzymes and TransferProteins Functions Lecithin - Cholesterol Acyl transferase - LCAT Esterifies the cholesterol (Cholesterol→ Cholesterol ester) content of HDL to prevent it from reentering the cells Acyl-CoA: Cholesterol Acyl transferase- ACAT Formation of cholesterol esters in cells ATP-Binding Cassette-1- ABC-1 Transfer of free CH from plasma membrane to ApoA-1 (HDL) Cholesterol Ester Transfer Protein - CETP Transfer of CE and TG b/w HDL & VLDL & LDL Phospholipids Transfer Protein -PLTP Transfers phospholipids b/w lipoproteins Scavenger receptor class-B type-1-SR-B1 Multi ligand receptor that binds not only HDL but VLDL & LDL also
- 16. LCAT: Lecithin-Cholesterol Acyltransferase ABC-1 : ATP-binding cassette-1 SR-B1: scavenger receptor class B type-1 CETP: Cholesterol Ester Transfer Protein ABC-1 Hepatic HDL receptor +
- 17. Significance of reversecholesterol transport – Cellular & lipoprotein cholesterol is delivered back to the liver – It prevents deposition of cholesterol in the tissues – anti-atherogenic property of HDL to protect LDL from oxidation due to the association of esterase enzyme paraoxanase with HDL – Paraoxanase may destroy oxidized LDL – HDL decreases the risk of coronary heart diseases
- 18. Disorders of lipoproteins (Lipoproteinemias/Hyperlipidemias ) (Frederick son classification of lipoproteinemias)
- 19. • It causescomplex & different disease mechanism, it classified into • Primary hyper-lipoproteinemia: – is completely genetic disorders. • Secondary hyper-lipoproteinemia: – is manifested due to other disorders (Nephrotic syndrome, type-II DM & cirrhosis of liver ) . • Coronary & cerebral vessels are more commonly affected • Deposition of lipid in subcutaneous tissue leads to xanthomas HYPER LIPOPROTEINEMIAS (Increased lipoproteins in the blood)
- 20. Lipoproteinemias Metabolic Defect Elevated -LpCH TG Clinical feature Type-I:Familial lipoprotein lipase deficiency Lipoprotein lipase & Apo C-II deficiency chylomicrons N ↑↑ Eruptive xanthoma, hepatomegaly & Abdominal pain Type –IIA: Familiar Hypercholesterolemia LDL receptor defect. Apo-B ↑se LDL ↑↑ N Atherosclerosis, CDA & Xanthelesma Type –IIB: Familiar Hypercholesterolemia Overproducti on of Apo-B LDL & VLDL ↑↑ ↑ Corneal arcus Type-I, IV & V: Hyper triglyceridemia, Type-IIa: Hyper cholesterolemia, Type-IIb & III: combined Hyperlipidemia
- 21. Lipoproteinemias Metabolic Defect Elevated -LpCH TG Clinical feature Type –III: broad beta disease Apo-E & Apo- CII broad beta – VLDL(LDL & IDL) ↑↑ ↑ Palmar xanthomas , atherosclerosis Type-IV: Familiar Hyper triaglycerolemia Overproduction of VLDL& Apo –C-II ↑sed VLDL ↑ ↑↑ Associated with diabetes, heart disease, obesity Type-V : Combined hyper lipidaemias / hyper triglyceridemia Secondary to other causes ↑sed VLDL & chylomicrons N ↑↑ Ischemic heart diseases & chronic pancreatitis Type-I, IV & V: Hyper triglyceridemia, Type-IIa: Hyper cholesterolemia, Type-IIb & III: combined Hyperlipidemia
- 22. Palmar xanthomas (Effects thepalms) Corneal arcus (Deposition of lipid in the peripheral cornea) Eruptive xanthoma, (small yellow nodules associated with deposition of TG . lesions and bumps that appear on the skin) Xanthelasma (yellow plaques deposits under the periorbital skin / near canthus of eyelid) Tuberous Xanthomas (deposition of yellow plaqes with TG& chol in tendons or elbows &knees) Acanthocytosis Irregular shaped RBCs with spikes on the outside
- 23. Lipoproteinemias Metabolic Defect Decreased - Lp CHTG Clinical feature Abeta- lipoproteinemia Apo-48 ↓ & Apo B- 100 ↓↓sed LDL is completely absent (TG is not incorporated into VLDL & Chylomicrons) ↓↓ ↓ -Malabsorption : causes mental & physical retardation. -Acanthocytes Familial α-lipo protein deficiency (Tangier’s disease) - Mutation in the ABC-1 protein -HDL↓↓↓ & -A–I ↓ N N “CE”are accumulated in tissues leads to Increased risk of CAD Large orange yellow tonsils & muscle atrophy Recurrent peripheral neuropathies HYPO LIPOPROTEINEMIAS (Decreased lipoproteins in the blood)
- 24.