LIPIDS AND LIPOPROTEINS LIPID CHEMISTRY AND CARDIOVASCULAR PROFILE

LIPIDS AND LIPOPROTEINS

LIPID CHEMISTRY AND CARDIOVASCULAR PROFILE � Main lipids in the blood are the triglycerides and cholesterol. � Insoluble in the water. � Transport in the blood is via lipoproteins

TRIGLYCERIDES � Glycerol with 3 attached fatty acids Exogenous source : Dietary � Endogenous : Liver and tissue storage � 95 % of body fat is triglycerides � Energy source when plasma glucose is decreased � Triglyceride catabolism is regulated by lipase, epinephrine and cortisol � � Triglycerides transported by Chylomicrons ( exogeneous ) and VLDL ( endogenous )

CHOLESTEROL � � � Found only in animals Important component of membranes, steroid hormones, bile and Vitamin D Exogeneous cholesterol comes from diet Endogeneous cholesterol is synthesized by the liver 70 % of cholesterol associated with cellular components 30 % is in the plasma ( ⅓ free form , ⅔ esterfied ) � � Transported by HDL and LDL 4

� Fatty acids are short to long carbon chained molecules � Saturated fatty acids � Unsaturated fatty acids � Phospholipids � � � Important components of cell membranes Lecithin and sphingomyelin are utilized to determine fetal lung maturity from amniotic fluid ( L / S Ratio ) Glycolipids � � Lipids with a carbohydrate component ABO antigen are glycolipids

LIPOPROTEINS Lipoprotein is a complex spherical structure that has a hydrophobic core wrapped in hydrophilic coating. 4 major classes of lipoproteins. Chylomicrons Very low density lipoproteins (VLDL) Low density lipoproteins (LDL) High density lipoproteins (HDL)

LIPOPROTEINS COMPOSITIONS

COMPOSITION OF LIPOPROTEINS Class Diameter (nm) % protein % triacylglyce rol % % cholesterol phospholipid & cholesterol ester HDL 5– 15 33 30 29 4 LDL 18– 28 25 50 21 8 IDL 25– 50 18 29 22 31 VLDL 30– 80 10 22 18 50 8 7 84 Chylomicro 100 -1000 <2 ns

CHYLOMICRON STRUCTURE

LDL Most core lipid in LDL is cholesterol ester. Apo. B 100 is only apolipoprotein in the surface.

LDL RECEPTOR � Also named as apo. B-100/apo. E receptors � LDL receptors exist in the liver and in most peripheral tissues � The complexes of LDL and receptor are taken into the cells by endocytosis, where LDL is degraded but the receptors are recycled � Number and function of the receptor shows LDL levels. � LDL cholesterol levels are positively related to risk of cardiovascular disease � Therefore, cholesterol in LDL has been called “bad cholesterol”

APOLIPROPROTEINS � Outer protein “shell” of the lipoprotein molecule � The protein – lipid interaction allows the water insoluble lipid to become soluble in plasma 12

CLASSES OF APOLIPOPROTEINS A, B, C, D, E are major classes � Subclasses: apo A-1, apo C-II � N. B. function of all apolipoproteins are not yet known � • Act as structural components of lipoproteins • Recognize the lipoprotein receptors on cell membrane surface as ligand • Activate/inhibit enzymes involved in lipoprotein metabolism

METABOLISM � Exogenous � Endogenous � Lipoprotein lipase � release FFA and glycerol from chylomicron and VLDL � Lecithin LCAT Cholesterol acyl transferase � Forms cholesteryl esters from free cholesterol and fatty acids

LIPID AND LIPOPROTEIN POPULATION DISTRIBUTIONS � Serum lipoprotein concentrations differ between adult men and women, � Primarily as a result of differences in sex hormone levels, � � Women having, on average, higher HDL cholesterol levels and lower total cholesterol and triglyceride levels than men. The difference in total cholesterol, however, disappears after menopause as estrogen decreases

HYPERCHOLESTEROLEMIA � Familial hypercholesterolemia (FH) (7. 5 - 12 mmol/L) Primarily LDL elevations � Synthesis may be normal but decrease or lack LDL receptors due to mutation in LDL receptor gene. � Therefore LDL builds-up in serum � Since cells cannot acquire from LDL therefore increase internal synthesis of cholesterol. � Tendon xanthomatas � Early occurrence of coronary artery disease � 1 8

HYPERTRIGLYCERIDEMIA � Triglycerides Borderline = 150 -200 mg/ dl � High 200 -500 mg/dl � Very High > 500 mg/dl � � Familial � hypertriglyceridemia Genetic � Secondary hypertriglyceridemia Hormonal imbalances � Imbalance between synthesis and clearance of VLDL � 1 9

HYPERTRIGLYCERIDEMIA � Generally caused by deficiency of LPL or LPL cofactor. (LPL hydrolyzes triglycerides in chylomicrons and VLDL) � Deficiency prevents processing and clearing of triglycerides � Elevated even with fasting 2 0

FAMILIAL COMBINED HYPERLIPIDEMIA � Presence of elevated levels of serum total cholesterol and triglycerides � Hepatic overproduction of apo B � Increased VLDL and LDL 2 1

FAMILIAL HYPERCHYLOMICRONEMIA � Genetic mutation of LPL or apo C-II gene � Recurrent abdominal pain � Pancreatitis

CLINICAL DISORDERS OF LIPID METABOLISM � Primary � Secondary

HYPERLIPIDEMIAS

SECONDARY Disease Lipid abnormality DM TG Alcohol TG CRF TG Drugs thiazide TG Hypothyroidism Cholesterol Nephrotic syndrome Cholesterol