Lipids in Clinical Chemistry
|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|
|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.|
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.
|Lipids include:|| Cholesterol|
|Saturated fatty acids|| Single bonded carbons|
Solid at room temp
|Unsaturated fatty acids|| Double bonded carbons|
Usually liquid at Room Temp
|Triglycerides|| Glycerol with 3 attached fatty acids|
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.
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|
|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.
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 defective Apo-B
|High TG / Normal Cholesterol|| Diet / lifestyle|
Secondary to diabetes, thiazide diuretics, Cushions, beta blockers, CRF/ nephrotic syndrome.
APo C III excess (interferes with LPL)
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