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What are the charcteristics
of lipids?
- 1. hydrogen-carbon bonds
- 2. hydrophobic and non polar
- 3. insoluble in water
- 4. soluble in nonpolar solvents
- 5. can be modified with polar elements generating amphiteric molecules
-
What is the most basic lipid unit?
Fatty acid
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What molecule consists of a COOH group attached to a variable length hydrocarbon
chain ; can be attached to other molecules such as glycerol or cholesterol, and
is considered one the most basic lipid units?
Fatty acids
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How do double bonds affect fatty acids? How about single bonds?
- 1.Double bonds cause fatty acids to become
- unsaturated.
- 2. Single bonds cause fatty acids to become
- saturated.
-
What fatty acids cannot be created in our bodies but are vital and igested for development and good health?
- Omega-6 (linoleic acid)
- Omega-3 (linolenic acid)
-
Describe the esterification of glycerol?
The result of the combination of a fatty acid with an alcohol (in this case glycerol). Usually 1, 2, or 3 fatty acids.
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What fatty acid ester (glycerol ester) is found in plant oils that incorporate unsaturated fatty acids, and are increased in serum after meals?
Triglycerides.
-
In the formation of glycerol esters, what molecule is linked to one carbon molecule in glycerol?
Phosphoric acid
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What is the major animal lipid that includes a backbone common to steroid hormones and vitamin D?
Cholesterol
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What lipid may be cytotoxic, where in the body most of it is esterified (linked to a fatty acid)?
Cholesterol
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What membrane lipid includes ceramide ans gnagliosides, and is involved in cell membrane integrity, and the CNS?
Sphingolipids
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What group of fatty acids include prostaglandins and thromboxanes, and are considered hormones synthesized from essential fatty acids at the site of action?
Eicosanoids
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What fatty acid includes Vitamins A, E, and K formed from combinations of 5 carbon units? Also includes thujone, an active ingredient of absinthe.
Terpenes
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What are some biological functions of proteins?
- 1. Fats and oils—forms of stored energy
- 2. Phospholipids and sterols—structural and membrane components (ex. myelin sheath, lipid bilayer)
- 3. Hormones
- 4. Enzyme cofactors
- 5. Electron carriers
- 6. Light-absorbing pigments
- 7. Hydrophobic anchors for proteins
- 8. Chaperones to help membranes fold
- 9. Emulsifying agents in the digestive tract
- 10. Intracellular messengers
-
List some of the possible membrane modifications?
Man alpha-(1-2), phosphoethanolamine, Gal4, GalNAc beta-(1-4), and fatty acids.
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Lipids are hydrophobic. How do they travel through the bloodstream to reach their destinations?
Lipids are bound in large particles called lipoproteins.
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What are separated proteins referred to as?
Apolipoproteins.
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What are lipoproteins composed of?
A phospholipid outer layer crossed by the proteins components and cholesterol, and a core composed of varying amounts of triglycerides and cholesterol esters.
-
What are the different classes of lipoproteins?
- 1. Chylomicrons
- 2. Very Low Density Lipoprotein (VLDL)
- 3. Low Density Lipoprotein (LDL)
- 4. High Density Lipoprotein (HDL)
- 5. Minor Classes: Intermediate Density Lipoprotein (IDL), Lipoprotein a (Lp(a))
-
How do we distinguish between lipoproteins?
- 1. Density
- 2. Particle size
- 3. Electrophoretic mobility
- 4. Chemical composition
-
What are the two major functions of lipoproteins?
1. Apo B-containing particles (lower density) including chylomicrons, VDL, IDL, and LDL distribute cholesterol and triglycerides to tissues.
2. Apo A-containing particles (higher density) including HDL return cholesterol from tissues to liver, where it is reused or excreted in the bile as bile salts (reduced CHD risk)
-
How are lipids delivered to tissues?
Through exogenous and endogenous routes.
-
What is the function of delivering lipids to tissues?
They provide triglycerides and cholesterol esters to cells.
-
What is the function of apolipoproteins during lipid delivery to tissues?
Apolipoproteins act as ligands for lipoprotein receptors and as activators for lipoprotein lipase.
-
Where are chylomicrons produced?
Chylomicrons are produced by the intestines following ingestion of dietary lipids.
-
What molecule is a major constituent of chylomicrons, adding turbidity to plasma after meals?
Triglycerides
-
What is the function of chylomicrons?
Chylomicrons interact with muscle and adipose tissue, where apoliproteins (especially C-II) activate cell membrane bound lipase which begins depleting chylomicrons of their triglycerides.
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What happens to cohylomicrons when they are finished in the tissues?
Chylomicrons are not completely depleted of triglyceride but when finished, they are taken up by the liver.
-
Are chylomicrons atherogenic?
No. LDLs are.
-
What is the function of lipoprotein lipase?
- 1. hydrolyzes triglycerides yielding free fatty acids.
- 2. Participates in LDL uptake by assisting in receptor-ligand interaction.
-
Where is VLDL produced?
The liver
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VLDL supplies tissues with triglycerides from what origin?
Triglycerides of hepatic origin.
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What molecule can produce turbid plasma even when only carbohydrate is taken in the diet? as the liver converts the carbohydrate into triglycerides?
VLDL. The liver converts the carbohydrate into triglycerides.
-
What protein is responsible for hydrolyzing triglycerides in VLDL resulting in progressively denser particles?
Lipoprotein lipase.
-
Are the later particles in the breakdown of VLDL atherogenic?
VLDL—>IDL—>LDL
Yes. Later particles in VLDL metabolism are atherogenic.
-
How are ApoB-100 and cholestryl esters hydrolyzed?
LDL binds to its receptor via ApoB-100, then the particle is internalized and merged into a lysosome.
-
What happens to cholesterol after it is metabolized from Cholesteryl ester in the lysosome?
The unesterfied cholesterol is available for membrane synthesis, hormone synthesis, and bile acid synthesis (in liver).
-
What products are down regulated as unesterfied cholesterol increases?
LDL receptors on the cells surface and further cholesterol synthesis.
-
Where is the majority of LDL taken up in the body?
75% is uptaken by the liver.
-
How is LDL produced?
LDL is produced by the action of lipoprotein lipase on VLDL and IDL.
-
What percentage of cholesterol esterfied?
50%
-
What happens when scavenger macrophages take up LDL?
Macrophages contribute to atheroclerotic plaques when they take up LDL ---> creating foam cells.
-
How is excess cholesterol removed from cells?
1. Liver produces nascent HDL particles composed mostly of ApoA-I and little lipid contecnt
2. Nascent HDL particles travel through body collecting esterfied cholesterol.
3. The liver strips the lipid laden HDL of its cholesterol and is either stored or excereted as bile salts.
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What protein is present in HDL cholesterol and can activate Lecithin Cholesterol Acetyltransferase (LCAT) which catalyzes esterification?
Apo A-1 (apolipoprotein)
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What protein is present in VLDL though LDL cholesterol and acts as a ligand for LDL receptors on cell membranes?
Apo B-100 (apolipoprotein)
-
What protein is present in Chylomicrons and is a product of the same gene as Apo B-100 but with different splicing?
Apo B-48 (apolipoprotein)
-
What set of lipoproteins are mostly present in chylomicrons, that may prevent hepatic uptake of chylomicrons until most of their triglyceride mass has been stripped by lipoprotein lipase?
Apo C
-
What set of lipoproteins are found in chylomicrons and LDL and act as a ligand for hepatic receptors?
Apo E
-
What set of lipoproteins can combine with Apo B-100 to create lipoprotein (a)?
Apo (a)
-
What protein is an emerging risk factor for coronary heart disease, where its heredity significantly controls Lp(a) levels, but most individuals have low levels?
Lipoprotein(a)
-
List lipid regulating enzymes:
- 1. Hepatic Lipase
- 2. Endothelial Lipase
- 3. Cholesterol Ester Transfer Protein
- 4. Phospholipid Transfer Protein
-
What samples can be used for measuring cholesterol, triglycerides, HDL-C, and calculated LDL-C?
Plasma or serum
-
Why is EDTA preferred over heparin if electrophoresis will be used on plasma samples?
Heparin alters the electrophoretic mobility of lipoproteins.
-
Plasma or serum may be frozen to preserve which components? (-70 degrees, no self-defrost)
Total cholesterol, triglycerides, and HDL-C
-
What lipid tests do not require fasting?
Total cholesterol and HDL-C.
-
Which lipid test requires fasting where due to chylomicrons not clearing from blood for 6-9 hours?
Triglycerides
-
How much sterol (cholesterol) in plasma is esterfied? How much is non-esterfied?
60-70% is esterfied, 30-40% is non-esterfied.
-
Cholesterol ester + H2O —> cholesterol + free fatty acid
is catalyzed by what?
cholesteryl ester hydrolase
-
Cholesterol + O2 —> cholest-4-en-3-one + H2O2
is catalyzed by what?
cholesterol oxidase
-
H2O2 + phenol + 4-aminoantipyrine —> quinone dye (500nm abs)
is catalyzed by what?
peroxidase
-
Triglycerides + 3H2O —> glycerol + 3 fatty acids
is catalyzed by what?
lipase
-
glycerol + ATP —> glycerophosphate + ADP
is catalyzed by what?
glycerokinase
-
glycerolphosphate + NAD —> dihodroxyacetone-pjosphate + NADH
is catalyzed by what?
glycerophosphate oxidase
-
NADH + tetrazolium dye —> colored product
is catalyzed by what?
diaphorase
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How would you correct for any free plasma glycerol on a glycerol assay?
Use a triglyceride blank to perform a glycerol assay, without lipase.
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What is the purpose of the two reagents used in a homogeneous assay to measure HDL-C?
Reagent 1 sequesters non-HDL lipoproteins and reagent 2 liberates HDL-C to measure cholesterol.
-
What does LDL contain in fasting plasma?
Cholesterol
-
Does HDL or VLDL contain cholesterol during fasting?
No
-
WHat is the friedewald formula?
LDL=TC-HDLC-Plasma TG/5 (mg/L)
A method to indirectly measure LDL by subtracting the amount of other cholesterol associated particles.
-
When would you see errors using the Friedewald formula?
When the triglycerol level is >= to 400mg/L.
-
What are is the purpose of the two reagents used in direct LDL-C measurement?
Reagent 1 sequesters non-LDL and reagent 2 releases LDL-C to measure cholesterol.
-
What are the optimal fasting levels for:
-Total cholesterol
-LDL cholesterol
-HDL cholesterol
-Triglycerol
- -Total cholesterol <=200mg/dL
- -LDL cholesterol <=100mg/dL
- -HDL cholesterol >=40mg/dL
- -Triglycerol <=150mg/dL
-
WHat factors contribute to elevated serum triglycerides?
- 1. excess weight/obesity
- 2. physical inactivity
- 3. cigarettes
- 4. alcohol
- 5. high carbohydrates
- 6. primary disease states
- 7. type II diabetes
- 8. chronic renal failure
- 9. drugs: corticosteroids, estrogen
- 10. genetic metabolic disorders
-
A grouping of factors that significantly increase risk for coronary heart disease and other vascular disease (e.g. stroke) is known as:
metabolic syndrome
-
What are the risk factors for metabolic syndrome?
- 1. abdominal obesity
- 2. atherogenic dyslipidemia
- 3. elevated triglycerides, small LDL particles, low HDl
- 4. raised blood pressure
- 5. insulin resistance
- 6. prothrombotic or proinflammatory states
-
What are the primary risk factors for Coronary Heart Disease?
- 1. genetic predisposition
- 2. family history of premature CHD in first degree relatives
- 3. hypertension
- 4. cigarettes
- 5. decreased HDL cholesterol
- 6. elevated triglyceride (VLDL, cholesterol)
- 7. increasing age
- 8. male gender
-
What are secondary risk factors for Coronary Heart Disease?
- 1. lack of exercise
- 2. obesity
- 3. stress
- 4. diabetes mellitus
- 5. elevated lipoprotein(a), IDL
- 6. postmenopausal
- 7. renal patients on hemodialysis
- 8. elevated homocysteine
-
What lipid is coronary heart disease based on where the optimal level is <=100,g/dL?
LDL cholesterol
-
What lipid is coronary heart disease based on where the optimal level >=40mg/dL?
HDL cholesterol
-
What protein is similar to plasmin and plasminogen, which function in thrombolytic pathways but does not induce thrombolysis, and may interfere with clot removal?
Apo(a)
-
What lipid is essentially LDL with apo(a) and linked to increased risk of coronary heart disease, including premature disease?
Lp(a)
-
The expression of this lipid has a genetic component and shows marked elevation in a small segment of the population:
Lp(a)
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This disorder has a primary (genetic) or secondary (from another condition) origin and is related to inappropriate levels of lipids in the blood:
Dyslipidemias
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