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

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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.

ChylomicronsVery low density lipoproteins (VLDL)Low density lipoproteins (LDL)High density lipoproteins (HDL)

LIPOPROTEINS COMPOSITIONS

COMPOSITION OF LIPOPROTEINS

Class Diameter (nm)

 % protein

 % cholesterol

 % phospholipid

 % triacylglycerol& 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

Chylomicrons 100-1000 <2 8 7 84

CHYLOMICRON STRUCTURE

LDL

Most core lipid in LDL is cholesterol ester.

ApoB100 is only apolipoprotein in the surface.

LDL RECEPTOR

Also named as apoB-100/apoE 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

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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 Cholesterol acyl transferase LCAT

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

M. Zaharna Clin. Chem. 2009

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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

M. Zaharna Clin. Chem. 2009

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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

M. Zaharna Clin. Chem. 2009

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FAMILIAL COMBINED HYPERLIPIDEMIA

Presence of elevated levels of serum total cholesterol and triglycerides

Hepatic overproduction of apo B Increased VLDL and LDL

M. Zaharna Clin. Chem. 2009

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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