Lipoproteins A lipoprotein is a biochemical assembly that contains both proteins and lipids, bound to the proteins, which allow fats to move through the water inside and outside cells. The proteins serve to emulsify the lipid molecules. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins.

Examples include the plasma lipoprotein particles classified under high-density (HDL) and low-density (LDL) lipoproteins. Enable fats to be carried in the blood stream, the transmembrane proteins of the mitochondrion and the chloroplast, and bacterial lipoproteins

Apolipoproteins Embedded in the lipoprotein shell Three functions 1. Serve as recognition sites for cell-surface receptors; allowing cells to bind and ingest the lipoprotein. 2. Activate enzymes that will metabolize the lipoprotein 3. ↑ structural stability of the lipoprotein

Apolipoproteins All lipoproteins that deliver lipids to peripheral tissues (nonhepatic tissues) contain apolipoprotein B-100 (Ex: VLDL, LDL) All lipoproteins that transport lipids from peripheral tissues back to the liver contain apolipoprotein A-I (Ex: HDL)

Types of Lipoproteins lipoprotein classes Classified according to density and electrophoresis migration Lipoproteins differ in their sizes, density, weights, chemical composition and artherogenicity (association with heart disease ) lipoprotein classes chylomicrons: take lipids from small intestine through lymph cells very low density lipoproteins (VLDL) intermediate density lipoproteins (IDL) low density lipoproteins (LDL) high density lipoproteins (HDL)

Lipoprotein Nomenclature and Composition CM VLDL IDL LDL HDL Major apoB apoB apoB apoB apoA-I Protein Major TG TG CE CE CE Lipid CM= chylomicron TG=triglyceride VLDL= very low density lipoprotein CE= cholesteryl ester IDL= intermediate density lipoprotein LDL= low density lipoprotein HDL= high density lipoprotein Apo = apolipoprotein

Lipoprotein Profile Cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter (dL) of blood. Desirable or optimal levels for adults with or without existing heart disease are: Total cholesterol: Less than 200 mg/dL. Low Density Lipoprotein (LDL) cholesterol: Less than 100 mg/dL. High Density Lipoprotein (HDL): 40 mg/dL or higher. Triglycerides: Less than 150 mg/dL.

Lipoproteins The HDL and LDL levels in the blood can be used to assess ones risk for atherosclerosis. High levels of HDL is considered good This is why HDL is sometimes referred to as “good cholesterol” > 40 mg/dL is good. High levels of LDL is considered bad This is why LDL is sometimes referred to as “bad cholesterol” > 100 mg/dL is bad.

Hyperlipidemia can lead to disease When there is too much cholesterol /LDL in body (because of diet and the rate at which the cholesterol is processed) it is deposited in arteries, including those of the heart, which can lead to narrowing of the arteries and heart disease. Studies of people with heart disease have shown that lowering cholesterol/LDL reduces the risk for dying from heart disease, having a heart attack, or needing heart bypass surgery or angioplasty.

Low cholesterol/LDL levels in your blood help keep you healthy by preventing heart attacks and strokes. Therefore, maybe eating foods that are low in cholesterol may ultimately be able to lower your risk for these diseases.

Lipids Metabolism

Transport of Lipoproteins in the Body

Transport of fats: VLDL moves triglycerides from liver to tissues. LDL transfers cholesterol to tissues from liver. HDL carries cholesterol from tissues to liver. Monoglycerides and fatty acids are absorbed by intestines - transported as chylomicrons in lymph system to blood.-Fat Blocker-Xenical (Alli) Dietary fat

Chylomicrons Transports exogeneous ( dietary ) triglycerides 90 - 95 % by weight is triglycerides Absent from fasting plasma Removed from the plasma within 6 hours by the liver Inadequate clearance produces a creamy layer on the plasma

Transport Chylomicrons – lipoproteins Transport primarily triglycerides from the GI tract to the liver. Travel through lymph and enter blood in chest Travel through the heart and then body Enzymes break off fatty acids from TG and deliver them to cells for energy or storage as TG Chylomicron remnants are then delivered to the liver

Transport In the liver Liver breaks down remaining TG and remakes them! Liver also makes cholesterol and other TG These TG and cholesterol are packaged with proteins to make VLDL

VLDL (Very Low Density Lipoproteins) Transports endogeneous triglycerides from liver to tissues 50 - 65 % by weight is triglycerides Excess dietary carbohydrates are converted to triglycerides by the liver

VLDL (very low density lipoprotein) Contain triglycerides (TGs) and some cholesterol Account for nearly all TGs in the blood Contain B-100 Deliver triglycerides from the liver to adipose tissues and muscles. TGs are hydrolyzed and removed by lipoprotein lipase. Results in free fatty acids for storage in adipose tissue or oxidation in cardiac tissue or skeletal muscle Remnants of hydrolysis are IDL (intermediate density lipoproteins), which can be transported to liver or converted to LDL High levels increases risk of pancreatitis

Transport VLDL enters blood VLDL delivers cholesterol and fatty acids to needy cells Density goes up as the fats leave the transport protein

LDL molecule

LDL (Low Density Lipoproteins ) Synthesized in the liver Transports cholesterol from liver to the tissues Formed from IDL, the remnants of VLDL Makes the greatest contribution to coronary atherosclerosis Oxidized LDL contributes to atherosclerotic plaque

Transport VLDL becomes LDL as it loses FA Low density lipoprotein LDL is high in cholesterol LDL circulates in blood delivering cholesterol to cells LDLs (low density lipoproteins) transport cholesterol, triglycerides and phospholipids from the liver to other tissues.

Account for 60-70% of cholesterol in the blood Contains B-100 LDL cholesterol is sometimes called bad cholesterol. High LDL cholesterol leads to a buildup of cholesterol in arteries. The higher the LDL level in your blood, the greater chance you have of getting heart disease. Account for 60-70% of cholesterol in the blood Contains B-100 Delivers cholesterol to peripheral tissues

Transport LDL “Bad” cholesterol Contributes to plaques when cholesterol “falls off” the LDL and is deposited on artery walls Plaques narrow arteries Raises blood pressure Increases risk of blood clots and heart attacks Low Density Lipoproteins (LDL) – is made by the liver and is comprised of cholesterol that is delivered to the cells in the body High levels of LDL is strongly correlated with heart disease

HDL (high density lipoprotein) “Good cholesterol” Contain cholesterol Account for 20-30% of cholesterol in the blood Some contain Apo I and Apo II Apo I is cardioprotective Transports cholesterol from the peripheral tissues back to the liver – promotes cholesterol removal Antiatherogenic

Transport HDL HDL transports cholesterol and other lipids back to liver for disposal Can pick up cholesterol from plaques Good cholesterol HDLs (high density lipoproteins) transport cholesterol and phospholipids back to the liver. High Density Lipoproteins (HDL) - made by the liver and picks up cholesterol from the cells fro recycling or excretion High levels of HDL is inversely correlated with heart disease It is protective HDL cholesterol is sometimes called good cholesterol. HDL carries cholesterol from other parts of your body back to your liver. The liver removes the cholesterol from your body. The higher your HDL cholesterol level, the lower your chance of getting heart disease.

HDL ( High Density Lipoprotein ) Transports excess cholesterol from the tissues back to the liver ( reverse transport ) Synthesized in the liver and intestines Composition 30% PHOSPHOLIPIDS 20% CHOLESTEROL 50% APOPROTEIN The “good “ cholesterol VLDL = Trig / 5

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

Arteriosclerosis Increased LDL and decreased HDL associated with increased plaque formation 1% decrease in LDL drops CHD risk 2% Treatment to reduce LDL below 100 mg/dL is effective in the stabilization and sometimes regression of plaques

Peripheral vascular disease (PVD) When plaque develops in arteries of the arms or legs Coronary artery disease (CAD) when it develops in the heart Cerebrovascular disease (CVD) when it develops in the vessels of the brain

Adult Reference Ranges For Lipids ANALYTE REFERENCE RANGE Total cholesterol 140-200 mg/dL HDL cholesterol 40-75 mg/dL LDL cholesterol 50-130 mg/dL Triglyceride 60-150 mg/dL

LDL = Total Cholesterol – HDL – Trig/5 LDL Methods Friedewald calculation Determine total cholesterol, total triglycerides and HDL as before VLDL is estimated as triglycerides/5 400 mg/dl is the upper limit for TG LDL = Total Cholesterol – HDL – Trig/5