11. Lipids and Lipoproteins Flashcards
What are the 4 roles of lipids?
- Source of energy
- Integral part of cell membrane that assist cell structure
- Converted to hormones or hormone precursors
- Insulators for nerve conduction and heat retention
What are the 6 different types of lipids?
- Fatty acids
- Triglyceride
- Phospholipids
- Cholesterol
- Cholesteryl esters
- Apolipoprotein
Are lipids soluble or insoluble in water?
Insoluble
Fatty acids are an integral part in what kinds of lipids (2)?
Triglycerides and phospholipids
Fatty acids can be acquired by
Body can make some fatty acids, and there are essential fatty acids acquired by diet
Fatty acids are composed of (saturated vs unsaturated)?
Fatty acids are long carbon chains joined by single (saturated) or double bonds (unsaturated) and a terminal carboxyl group
What is triglyceride composed of?
Composed of 3 fatty acids and a glycerol molecule
Triglycerides comprises what percentage of fat stored in tissue?
Triglycerides comprises 95% of fat stored in tissue
Triglycerides can be exogenous or endogenous, or both?
Triglycerides can be exogenous (come from diet, plant/animal sources) or endogenous (synthesized by body)
What are phospholipids composed of? What is a term used to describe phospholipids?
Composed of two fatty acid molecules (hydrophobic) and a hydrophilic head (phosphate-containing group attached to a glycerol molecule)
Amphipathic (has both hydrophobic and hydrophilic parts)
Lipids are produced in the
Liver
What is the function of phospholipids?
Crucial for formation of permeability of cell membrane
Cholesterol can be acquired exogenous. They are found in plant products, animal products, or both?
Cholesterol can only be found in animal products
What are the 4 functions of cholesterol?
- Promote fat absorption in intestine by forming bile acids
- Make hormones
- Transforms Vitamin D in skin
- Component of cell membranes
Cholesterol can be made in the body (endogenous). How?
Produced in the hepatocytes, generated from acetyl-CoA
Most serum cholesterol is in the form of ___________
Cholesterol esters
Where are cholesterol esters located?
They are located in the center of lipoproteins (high-density lipoprotein (HDL), low-density lipoprotein (LDL))
What are lipoproteins and what is their function? What is the difference between apolipoprotein and lipoprotein?
Group of soluble proteins that combine with varying amounts of lipids in the blood, for transportation. Apolipoproteins are proteins that bind lipids to form lipoproteins.
What are the different lipids in a lipoprotein (5)?
- Apolipoproteins
- Triglycerides + 3. cholesterol ester
- Phospholipid
- Free cholesterol
What are the four major categories of lipoproteins from largest to smallest?
- Chylomicrons
- VLDL: very low density lipoproteins
- VDL: low density lipoproteins
- HDL: high density lipoproteins
Which lipoprotein is the largest?
Chylomicron
Why is chylomicron the least dense lipoprotein?
They have the lowest protein-to-lipid ratio (being about 90 percent lipid) and therefore the lowest density.
Chylomicron is mostly composed of?
Triglyceride
VLDL is composed of what?
Half is composed of triglycerides, and equal amounts of phospholipids and free cholesterol, and some apolipoproteins
LDL is composed of what?
Half composed of free cholesterol. Other half composed of equal amounts of phospholipid and apolipoproteins, and some triglycerides
HDL is composed of what?
Equal amounts of free cholesterol, phospholipid, and apolipoproteins. With little triglyceride
Which lipoprotein is considered the bad cholesterol and why?
LDL is lethal
Delivers cholesterol to cells
Which lipoprotein is considered good cholesterol and why?
HDL is helpful
HDL remove excess cholesterol from cells
What are the 4 different types of apolipoproteins?
- Apo A1
- Apo B
- Apo C
- Apo E
Which apolipoprotein is the major protein on HDL?
Apo A1
Apo B is the principal protein on which lipoprotein?
LDL, VLDL, and chylomicrons
What is the difference between Apo B-48 and Apo B-100?
Apo B-48 is synthesized in the intestine and on chylomicrons. Apo B-100 is synthesized primarily in the liver and on LDL and VLDL
What is the function of Apo C? Apo C is on which lipoproteins?
Activates lipoprotein lipase (LPL) to break down triglycerides. On chylomicrons, VLDL, and HDL.
What is the function of Apo E?
Promotes binding of LDL, VLDL
What are the three different pathways of lipid metabolism?
- Exogenous pathway
- Endogenous pathway
- Reverse cholesterol transport pathway
Which lipoprotein is involved in exogenous pathway?
Chylomicrons
Describe the exogenous pathway
Exogenous pathway: transport of dietary lipids.
Dietary triglycerides, phospholipids, and cholesterol absorbed in small intestine. Chylomicron transports these to liver via capillary. In capillary, lipoprotein lipase (LPL) breaks down triglycerides into free fatty acids taken up by adipose tissue.
Chylomicron remnants take up by liver. Lysosomal enzymes break down remnants to form free fatty acids, free cholesterol
Some cholesterol converted to bile acids. Bile acids and free cholesterol are directly excreted into bile, but not all exit the body (half reabsorbed by intestine, remainder found in stool)
Describe the endogenous pathway
Endogenous pathway: transport of hepatic-derived lipids
Liver forms VLDL using free fatty acids and cholesterol. VLDL is secreted into circulation via capillary. In capillary, lipoprotein lipase (LPL) breaks down triglycerides into free fatty acids taken up by adipose tissue. This forms IDL remnant (composed of less triglycerides).
IDL remnant is absorbed in liver. Half remnants are taken up in the liver, and half are converted into LDL in the liver. LDL is released into circulation to peripheral cells and tissue to deliver cholesterol. Some LDL can attract macrophages, which are phagocytized and turn into foam cells that deposit in atherosclerotic plaques.
Which lipoproteins are involved in the endogenous pathway?
VLDL and LDL
Describe the reverse cholesterol transport pathway
HDL is synthesized in the liver and picks up excess cholesterol from peripheral cells.
HDL can transport back to the liver, or give cholesteryl esters to other lipoproteins chylomicrons/VLDL remnants
Concentration of lipids differs between men, women, and children, due to ________ and ________
Due to sex hormone concentration and age
When men and women age, there is an increase in what lipids (2) and what lipoprotein (1)
Increase in total cholesterol and triglyceride, and LDL
Women generally have higher amounts of what lipoprotein (1) and lower amounts of what lipids (2)?
Women have higher HDL, and lower cholesterol and triglyceride
What is the defintion of dyslipidemias?
Disease associated with abnormal lipid concentrations
Dyslipidemias are subdivided into two major categories, and is usually a result from what condition?
Hyperlipoproteinemias/hyperlipidemia and Hypolipoproteinemias/hypolipidemia. Dyslipidemias are usually due to coronary artery disease/arteriosclerosis
Dyslipidemias can be acquired, congenital, secondary, or all of the above?
They can be acquired (environmental/lifestyle imbalance), congenital (genetic abnormalities), and secondary (due to other diseases)
What is arteriosclerosis, and which lipoprotein is often associated with this and how?
Disease from the deposition of lipids in artery walls. LDL that has entered the artery wall attracts and is engulfed by important immune system cells called macrophages that ingest, or “eat,” LDL particles. LDL-laden macrophages become foam cells that promote inflammation and further the development of atherosclerotic plaques.
Hyperlipoproteinemia is a result of what?
Result of malfunctions in synthesis, transport, or catabolism of lipoproteins. Resulting in elevated lipoprotein levels
What are the three divisions of hyperlipoproteinemia?
- Hypercholesterolemia
- Hypertriglyceridemia
- Combined of the two
What are clinical symptoms of hypercholesterolemia?
- Heart attacks occur at early age (teenage years, genetic)
- Patient exhibit xanthomas, which are cholesterol deposits under skin
- Cholesterol range from 300-1000 mg/dL
What is xanthomas?
Seen in patients with hypercholesterolemia, cholesterol deposits underneath skin
Which lipoprotein is elevated in hypercholesterolemia?
LDL
Hypertriglyceridemia is caused by (3):
Genetic:
1. Imbalance between synthesis and clearance of VLDL in circulation (elevated)
- Deficiency of apo-C or LPL
- Chylomicrons cannot be cleared and triglycerides remain high
- Normal function of LPL to hydrolyze triglycerides carried in chylomicrons and VLDL to give cells energy (cholesterol)
Secondary causes:
3. Hormonal abnormalities in pancreas, adrenals, pituitary and of diabetes mellitis
Hypertriglyceridemia is influenced by what hormones (7)?
- Insulin
- Glucagon
- Pituitary growth hormone
- Adrenocorticitropic hormone (ACTH)
- Thyrotropin
- Epinephrine
- Norepinephrine
What is the normal reference range of triglycerides? What is considered high?
Reference: 60-150 mg/dL
Borderline: 150-200 mg/dL
High: 200-500 mg/dL
What is the result of hypolipoproteinemia?
Low levels of lipoproteins
What are the two forms of hypolipoproteinemia and each of them have low levels of what lipoprotein?
Hypoalphalipoproteinemia- decrease in HDL
Hypobetalipoproteinemia- decrease in LDL
What is Abetalipoproteinemia? What is the results of it (3):
Absence of lipoproteins containing Apo-b (includes LDL, VLDL, chylomicrons)
- Inability to absorb fat/ fat absorption problems
- Difficulty weight gain and growth
- RBC membrane defects
Abetalipoproteinemia usually affects what demographic?
Infants
Where is lipoprotein lipase (LPL) found? What is the result if it does not function properly?
LPL primarily found in capillaries, serum triglyceride levels will rise if LPL does not function properly because it hydrolyzes triglycerides
If there is lack of Apo B receptors on cell surfaces, there will be an increase or decrease in cholesterol levels?
Increase
What is Tangier disease?
Tangier disease is an inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood.
What is the appropriate specimen for lipid analysis?
Fasting serum specimen (preferred 12 hr fast)
Why should lipemia be avoided in lipid analysis specimen?
Fat droplets suspended in a solution, lipemia affects assays by affect absorbance due to refraction of light. Shorter wavelengths show greater refraction, showing greater absorbance. Apparent absorbance decreases as wavelength increases due to refraction (more transmitted light)
What can be done to decrease plasma turbidity of high plasma lipid concentrations that interfere with spectrophotometric methods?
Lipoproteins can be spun down using special centrifuge (Ultracentrifuge)
A lipid panel can be ordered to evaluate concentrations. What does the panel consist of (4)?
- Total cholesterol
- LDL cholesterol
- HDL cholesterol
- Triglycerides
When measuring total cholesterol, what is the pro and con of using colorimetric methods?
Pro: less costly
Con: subject to interfering substances and may require extraction steps and strong acids (time-consuming)
What is the classic colorimetric method to measure total cholesterol?
The Liebermann–Burchard test
What is the Liebermann–Burchard test, what does it use, what does it produce?
It is the classic colorimetric method of determining total cholesterol. Uses sulfuric and acetic acids, resulting in a green color proportional to cholesterol concentration
What factors affect cholesterol levels (HDL & LDL levels) and how (3)?
- Thyroxine level inversely affects cholesterol levels
- Hypothyroid (low production thyroxine) have hyper cholesterol
- Hyperthyroid (high production thyroxine) have hypo cholesterol - Post-menopausal women, ovaries no longer produce much estrogen and estrogens mainly come from fat tissue, so there is increased cholesterol
- Pregnancy - altered endocrine function resulting in increased cholesterol
(Hepatitis, nephrotic syndrome, emotional stress, diabetes mellitus can also be factors)
What is the reference range of total cholesterol?
Varies with age, sex, diet. Should be <200 mg/dL
How is HDL cholesterol analyzed? Describe the procedure.
When serum is combined with dextran sulfate or phosphotungsate acid with magnesium chloride, all beta- lipoproteins (LDL and VLDL) are precipitated. The HDL fraction (alpha- fraction) remains in the supernatant. The supernatant is then treated as a sample and assayed for cholesterol by an enzymatic method.
What is a drawback of the precipitation method for HDL cholesterol analysis?
Elevated triglyceride levels results in overestimation of HDL. So many mabs will not perform HDL testing when triglyceride concentrations exceed 400 mg/dL
What is the reference, borderline, and high risk range of HDL?
Triglyceride measurements can use what type of methods (2)?
Enzymatic and colorimetric methods
Enzymatic method for triglyceride measurement involves which enzymes (3)? What does it form?
- Lipase
- Glycerol Kinase
- G6PD
Forms NADH
Colorimetric method for triglyceride measurement involves formation of what?
Hydrogen peroxide
Dextran sulfate or phosphotungsate acid with magnesium chloride is used for what type of method?
HDL analysis, precipitation reaction
Lipase, glycerol kinase, and G6PD are used for what method?
Enzymatic method for measuring triglycerides
What is the reference, borderline, high, and very high range for triglycerides?
Why is the direct measurement of LDL uncommon (calculation preferred)?
Because of technical difficulties.
What is the most common way of determining LDL concentration?
The Friedewald estimation (calculation)
What is the equation for the Friedewald calculation?
LDL = Total cholesterol - (HDL + VLDL) VLDL = Triglycerides/5
Lipids are seen in stool. Normal adult with normal diet should not have more than _________ of lipids per day in feces
Should not have more than 6 grams of lipids per day in feces
Increased levels of lipids in stool seen in children is due to? How about adults?
Increased levels seen in children with malabsorption and adults with pancreatic insufficiency
What test can be done to evaluate the lipid content in stool?
72 hour fecal fat quantitative test
