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Lipids in Clinical Chemistry

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What is a lipoprotein?
Molecules that interact with water insoluble fat molecules ad tansports them in the plasma. They allow the to be dissolved in the plasma.
What are the four types of proteins?
Chylomicrons
VLDL
LDL
HDL
Chylomicrons
Transports dietary triglycerides from the GI tract to the liver.
Absent from fasting plasma
Removed from the plasma within 6 hours by the liver.
Inadequate clearance produces a creamy layer on plasma
Very Low Density Lipoprotein VLDL
Transports triglcerides from the liver to the tissues for storage and energy.
Excess dietary carbs are convertd to triglycerides by the liver.
Low Density Lipoprotein LDL
Transports cholesterol to the peripheral tissues.
BAD cholesterol
50 - 65% by weight is triglycerides
LDL= T.cholesterol - (HDL +VLDL) Tri / 5
High Density Lipoproteins HDL
Transports cholesterol away from the peripheral tissues to the liver.
Synthesized in the liver and intestines.
GOOD cholesterol
Lipids include:
Cholesterol
Triglycerides
Phospholipids
Glycoproteins
Saturated fatty acids
Single bonded carbons
Solid at room temp
Animal sources
Unsaturated fatty acids
Double bonded carbons
Usually liquid at Room Temp
Plant sources
Triglycerides
Glycerol with 3 attached fatty acids
Dietary source
Liver and tissue storage
Triglycerides
95% of the bodys fat
Energ source when plasma glucose is decreased
T. catabolism is regulated by lipase, epinephrine and cortisol.
Transported by chylomicrons and VLDL
Cholesterol
Found only in Animals
Important component of membrane, steroid hormones, bile and Vit. D.
Dietary source
synthesized by the liver
Cholesterol
70% is associated with cellular components
30% is in the plasma (1/3 free form, 2/3 esterfied)
Transported by HDL and LDL
Phospholipids
Important components of cell membranes
Lecithin and sphingomyelin are utilized to determing fetal lung maturity and amniotic fluid (L/S ratio)
Glycolipids
Lipids with a carbohydrate component
ABO antigens are glycolipids
Apoliproproteins
*Outer protein shell of lipoprotein
*The lipid protein interactions allows the water insoluble lipid to become soluble in plasma.
*Responsible for the interactions with cell membranes and enzymes to transport lipids to specific locations.
HDL composition
30% Phospholipids
20% Cholesterol
50% Apoprotein
What major protein found in HDL?
Apo - A1 HDL
What Apolipoprotein is associated with high risk of CVD?
Apo - B LDL
What Apolipoprotein is associated with chylomicron remnants and renal failure?
Apo - C
Activates lipoprotein lipase?
Apo - C2
The exogenous pathway involves primarily which lipoprotein?
Chylomicrons
Chylomicron emnants are catabolized and channeled in what three pathways?
Synthesized VLDL, Released to form bile acids, Stored as cholesterol ester.
Lipoprotein physiology and metabolism
*Water insoluble lipids are digested into more water soluble.
*Triglycerides are digested into fatty acids.
*Cholesterol esters are converted into free cholesterol
*Fatty acids are converted into triglycerides by the liver and adipose tissue.
Lipoprotein physiology and metabolism
Most cholesterol synthesis occurs int the liver.
Most cholesterol lowerin drugs target this synthesis.
Cholesterol is a main component of bile (needed for dietary absorption of fat)
Exogenous Pathway
Transport of dietary lipids, mostly tge chylomicrons transportation of triglycerides to the liver.
Endogenous Pathway
Transportation of lipids from the liver to the tissues VLDL and LDL
Effects of Hormones (Insulin)
Decreases plasma glucose
Inactivates lipase which dec lipolysis and the catabolism of trigs to fatty acids/ glucose.
Stimulates lipogenesis (FA to Trigs)
Helps make fat
Hyperlipidemia
Standing plasma test for chylomicrons:
Plasma at 4C overnight
*Chylomicrons accumulate as floating cream layer.
*Chlyomicrons in fasting plasma are abnormal.
Normal Target Ranges
Total Cholesterol - < 200 mg/dl
HDL - > 35 mg/dl
LDL - < 130 mg/dl
Reference Ranges
T. cholesterol - 140-200 mg/dl
HDL - 30 - 75 mg/dl
LDL - 55-130 mg/dl
Trigs - 65- 155 mg/dl
Functions of Apolipoproteins
Activate enzymes involved in lipid metabolism (LCAT, LPL).
Maintain structural integrity of lipid/protein complex.
Delivery of lipids to cells via reognition of cell surface receptors.
Dyslipoprteinemias
Secondary or primary causes.
Secondary causes include starvation, liver disease, renal failure, diabetes, hypothyroidism, lipodystrophies, and drugs. Primary causes Inc. production, Defective processing, Defective cellular uptake, and inadequate removal.
Dyslipoproteinemias
Hyperchylomicronemia:
LPL deficiency
Apo C - II deficiency
High Cholesterol / High LDL
Diet / lifestyle
Secondary to hypothyroidism or nephrotic syndrome
(disruption of Apo - B metabolism)
Polygenic: (means we dont know)
Familial hypercholesterolemia
Familial defective Apo-B
Rare disorders
High TG / Normal Cholesterol
Diet / lifestyle
Secondary to diabetes, thiazide diuretics, Cushions, beta blockers, CRF/ nephrotic syndrome.
Familial hypertriglyceridemia
APo C III excess (interferes with LPL)
LPL deficiency
APo C II deficiency
High cholesterol / TG
Obesity
Secondary to steroids, Cs, hypothyroidism, CRF.
Familial combined hyperlipidemia.
Perioxisome proliferator activator receptor.
Dysbetalipoproteinemia (type III)
Hepatic lipase deficiency ( rare)
Low cholesterol / Low- Normal HDL
Abeta lipoproteinemia - APO B degraded after synthesis causes fat malabsorption.
Hypobetaproteinemia - genetically defective Apo B.
Chylomicron retention disease.
High HDL
Lifestyle (Ethanol)
Secondary to phenytoin, phenpbarbitol, rifampicin and estrogens.
Cholesteryl Ester Transfer Protein defects