Lipids and Lipoproteins

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1

lipids

organic compounds which are actually or potentially esters of fatty acids; soluble in organic solvents and nearly insoluble in water (hydrophobic); rich source of energy and provide energy storage; integral to cell membrane

2

major lipids

fats, phospholipids, and glycolipids

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fatty acids

short to long carbon chained molecules terminating in a carboxyl group

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saturated fatty acids

no double bonds between carbons (lay flat on top of each other and build up - plaque); solid at room temperature; animal sources

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unsaturated fatty acids

double bonds between carbon bonds (cannot lay tightly and pack together); usually liquid at room temperature; plant sources;

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cholesterol

steroid; a type of fat found in the blood; important in cell membranes, organs and tissues, used to make hormones, vitamin D, forms acids that are needed to absorb nutrients from bile; not a food source; not water soluble; transported by HDL and LDL

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steroid

an unsaturated alcohol containing four rings and single side chain tail

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triglycerides

glycerol with 3 fatty acid chains; 95% of body fat; energy source when plasma glucose is decreased; catabolism regulated by lipase, epinephrine and cortisol

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dietary

exogenous triglyceride source

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liver and tissue storage

endogenous triglyceride source

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chylomicrons

transport exogenous triglycerides

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VLDL

transport endogenous triglycerides

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phospholipids

similar to triglycerides, except with only two esterified fatty acids; third position on glycerol backbone contains phospholipid head group; cell membrane components; lecithin and sphingomyelin utilized to determine fetal lung maturity from amniotic fluid (L/S ratio)

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amphipathic

molecules having non polar region (hydrophobic) and polar region (hydrophilic)

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glycolipids

lipids with carbohydrate component; ABO antigens

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apolipoprotein

outer protein shell of lipoprotein molecule; classified into five categories: (Apo A, B, C, D, and E); protein allows water insoluble lipids to become soluble in plasma; responsible for interactions with cell membranes and enzymes to transport lipids to specific locations

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lipoproteins

classified according to density and ELP migration; differ in size, weight, composition, and artherogenicity (association with heart disease); four types: chylomicrons, VLDL, LDL, and HDL)

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chylomicrons

largest and least dense lipoprotein (1200nm); produced by intestine; delivers dietary lipids to hepatic and peripheral cells; 90-95% is triglycerides; transports exogenous triglycerides; absent from fasting plasma; removed from plasma by liver within 6 hours; inadequate clearance produces creamy layer on plasma

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VLDL (Very low density lipoproteins)

transport endogenous triglycerides from liver to tissues; 50-65% by weight is triglycerides; excess dietary carbohydrates are converted to triglycerides by the liver

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LDL (Low density lipoproteins)

transports cholesterol from liver to tissues; synthesized in the liver; approximately 50% by weight cholesterol; most atherogenic lipoprotein; bad cholesterol

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HDL (high density lipoproteins)

transports excess cholesterol from the tissues back to the liver (reverse transport); synthesized in the liver and intestines; composition 30% phospholipids, 20% cholesterol, and 50% apoprotein; good cholesterol

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lipid metabolism

insoluble digested into more soluble compounds in the GI tract

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triglyceride metabolism

digested into fatty acids

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cholesterol-ester metabolism

converted into free cholesterol

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fatty acid metabolism

converted into triglycerides by the liver and adipose tissue

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cholesterol metabolism

synthesized in the liver; main component of bile needed for absorption of fat

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lipid absorption

converted to amphipathic lipids -> form micelles in intestinal lumen -> come into contact with microvillus membranes of intestinal mucosal cells and -> absorbed

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exogenous pathway

chylomicrons interact with proteoglycans on surface of capillaries in various tissues in circulation; free fatty acids and glycerol from hydrolysis of triglycerides by lipoprotein lipase can then be taken up

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endogenous pathway

VLDL loses core lipids, causing dissociation and transfer of apolipoproteins and phospholipids to other lipoprotein particles -> VLDL converted to remnant -> transformed by lipolysis into LDL -> half converted to LDL, remainder taken up as VLDL remnants by liver remnant receptors

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reverse cholesterol transport pathway

HDL removes excess cholesterol from cells

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insulin

decreases plasma glucose; inactivates lipase decreasing lipolysis and the catabolism of triglycerides to fatty acids and glucose; stimulates lipogenesis; helps make fat

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lipogenesis

the conversion of fatty acids to triglycerides

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diabetes mellitus

insulin deficiency promotes release of fatty acids and their conversion to triglycerides by the liver

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coronary artery disease

importance of measuring lipoprotein; the #1 cause of premature death in the US

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lipid testing

standardized to provide consistent results that can be utilized for the risk assessment of CAD

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cholesterol levels

high levels associated with heart disease; not affected by a single meal, but by long term pattern of eating; elevated during pregnancy and until 6 weeks post partum; can be increased by anabolic steroids, beta blockers, epinephrine, oral contraceptives, and vitamin D

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below 200 mg/dL

good cholesterol level indicating low risk of heart disease

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240 mg/dL

borderline cholesterol; at risk of heart disease if any higher

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HDL testing

precipitated from plasma; dextran sulfate added to plasma; HDL precipitates and is centrifuged to the bottom; supernate contains only HDL; measured using conventional total cholesterol methodology; affected by elevated triglycerides

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>400mg/dL

elevated triglycerides

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LDL Testing

bad cholesterol; atherogenic; direct measurement is uncommon because of technical difficulties

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Friedewald estimation (calculation)

total cholesterol, total triglycerides and HDL with routine procedure; estimate: Cholesterol - (HDL+VLDL (trig/5))

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VLDL

calculate by taking triglyceride level divided by 5

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arteriosclerosis

#1 cause of death and disability; cholesterol deposits in coronary arteries occlude blood flow

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coronary artery disease

arteriosclerosis of the heart

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peripheral vascular disease

arteriosclerosis of the arms and legs

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cardiovascular disease

arteriosclerosis of the brain

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plaque formation

associated with increased plasma cholesterol and plasma LDL and decreased HDL

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<200 mg/dL

total cholesterol target range

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>60 mg/dL

high density cholesterol target range

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<130 mg/dL

low density cholesterol target range

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<150 mg/dL

triglyceride target range

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140-200 mg/dL

total cholesterol reference range

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40-60 mg/dL

HDL reference range

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55-130 mg/dL

LDL reference range

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<150 mg/dL

normal triglyceride reference range

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150-199 mg/dL

borderline high triglyceride level reference range

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200-499 mg/dL

high triglyceride level reference range

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> or = to 500 mg/dL

very high triglyceride level reference range

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ultracentrifuge

method to test high plasma lipid concentrations that cause excessive plasma turbidity and interfere with spectrophotometric methods; lipoproteins spun down specially to spin lipids to the outside of the donut

61

apolioproteins

protein shells that interact with lipids and allow them to be water soluble

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HDL transport

transports cholesterol away from tissues to the liver

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LDL transport

transports cholesterol to the tissues from the liver

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VLDL transport

transports endogenous triglycerides from the liver to the tissues

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chylomicrons transport

transports exogenous triglycerides from GI tract to the liver

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fasting specimen

type of specimen required for accurate lipoprotein results