Lipids & Lipoproteins Flashcards
What are lipids?
Substances insoluble in water because they contain nonpolar C-H bonds.
What do lipids include?
Fats, steroids, phospholipids, others
What is the lipid composition of food?
98% TG (95% fatty acid and 5% glycerol)
2% cholesterol, phospholipids, steroids, fat soluble vitamins
List the functions of lipids
Energy source
Hormone, hormone precursor
Cell membrane components
Assist in digestion
What are the three phases of lipid physiology?
Digestive phase
Absorptive phase
Transport phase
What happens on the digestive phase?
TG are broken down by lipase in the liver with the help of cholic acid from liver bile. Lipids are surrounded by bile acid which emulsifies them into micelles.
What happens in the absorptive phase?
Lipids are absorbed freely in the small intestine in the form of free fatty acids and monoglycerides (glycerol with one FA tail).
What is a monoglyceride?
Glycerol containing one FA tail.
What happens in the transport phase?
Long fatty acids and cholesterol are reassembled and transported as chylomicrons and moved through the lymphatic system of the small intestine , transported to tissue for use or storage.
Short fatty acids are bound to albumin to head to all tissues as free fatty acids. They are moved out of adipose tissues after lipolysis from stored TG.
What is cholesterol?
Lipid made by hepatocytes of the liver fro, two acetate groups; acetatyl coa and acetoacetyl-coa. (90% of it)
What are the functions of cholesterol?
- Hormone precursor for cortisol, estrogen, testosterone.
- Cell membrane constituent
How does cholesterol circulate?
In the form of cholesterol esters
In what form is cholesterol trasnsported?
HDL
LDL
What about dietary cholesterol?
Only a small amount of it is absorbed.
Described the physiology of cholesterol
- Firstly, cholesterol must be solubilized (emulsified) into micelle form by bile acids (detergent)
- After being absorbed, cholesterol is packed in chylomicrons.
- Chylomicrons carry cholesterol to the liver and rest of the body.
What cells make cholesterol?
All cells, especially those of the liver.
What is the enzymatic committing and rate limiting step in the formation of cholesterol?
HMG COA reductase
What is the drug that usually inhibits this hmg coa reductase enzyme?
Statin
What happens to cholesterol in tissues?
Cholesterol is esterified and bound to a lipoprotein core in the circulation and moved into cells for various functions
What happens to cholesterol in the liver?
It is converted to bile acids in the liver, then recycled or excreted in feces.
What are triglycerides?
Lipids made up of fatty acid and glycerol. Can be long or short
What are the functions of triglycerides?
Organ insulation
Energy source
Storage (offering free FA to the Krebs cycle)
What percentage of stored fat is TG?
95%
What is the physiology of TG?
When eaten, they are digested by lipase, emulsified, and then reformed in the intestinal cells and packaged into chylomicrons.
What is the source of TG?
Most of TG is gotten fro, diet, but a small part is synthesized in the liver
Why is fasting important for a TG test?
Serum levels are affected by diet.
In what form are TG transported?
VLDL and chylomicrons
Describe Fatty Acid metabolism.
- FA travel in blood bound to albumin and are made into parts of TG, phospholipids or cholesteryl esters.
- Excess are stored in fat tissue (adipocytes)
What is the function of FA?
Provide acetyl coa to the Krebs cycle which drives the formation of ATP in the mitochondria.
What does the Krebs cycle do?
Drive the formation of ATP in the mitochondria
What are phospholipids?
These are polar lipids with prosthetic phosphoric acid groups, and are water soluble
What is the function of a phospholipid?
- Cell membrane constituent
- Major component of lipoprotein, surrounding fats and gluing them to the core.
What are lipoproteins?
The form in which lipids are transported to distant tissues to complete their functions.
Why do lipids need lipoprotein?
Lipids are so hydrophobic so there must be some hydrophilic adaptation that allows the, to move in plasma, and these lipoproteins are that hydrophilic adaptation.
What is the composition of lipoproteins?
Complex structures with an outer monolayer of protein (apolipoprotein A-E), phospholipids (polar lipids), as well as an inner core of lipids.
What is the function of a lipoprotein?
To transport and help metabolize lipids.
Give the classes of lipoproteins
Chylomicrons VLDL LDL HDL Apolipoprotein (A)
What are apolipoproteins?
The protein component of lipoprotein.
What are the classes of apolipoprotein?
APO A-E
What are the functions of apolipoprotein?
Maintain integrity of lipoprotein
Control enzyme activity and metabolism of cells
Bind cell surface receptors and uptake lipids into cells
How many apolipoprotein are there on average to each lipoprotein?
1-2 apolipoprotein per lipoprotein
What do deficiencies of apolipoprotein cause?
Change in lipid fractions in the blood
Provide conditions resulting from deficiencies in apolipoprotein.
Familial lipoprotein lipase deficiency
Tangier’s disease
Different APO E alleles linked to Alzheimer’s
What is the apolipoprotein for LDL?
APO-B100
What are Chylomicrons?
Large molecules that are mainly made up of TG and contain APO B-48
What is the main function of chylomicrons?
Transporting lipid absorbed from food to tissue and liver
Where do chylomicrons originate?
In the intestinal tract.
What substance accounts for the milking apperance in a pipe mic specimen?
Chylomicrons
What are VLDL?
Smaller than chylomicrons made up of mainly TG and then cholesterol.
Where are VLDL synthesized and for what use?
In the liver, for transporting TG to tissues
Where do chylomicrons deliver fat from and to?
From GI tract to liver
Where do VLDL deliver fat from and to?
From liver to tissue
What are VLDL degraded to form?
VLDL are degraded in circulation to form LDL with remaining cholesterol
What are LDL?
Lipoproteins formed from the degradation of VLDL in circulation.
What is the composition of LDL?
Has mainly cholesterol and very little TG
Why is LDL called a bad cholesterol?
Not only does it contain mostly cholesterol and very little TG or protein, it is highly associated with increased risk of coronary artery disease and atherosclerosis.
What does a lack of APO-B100 receptor on a cell lead to?
Familial hypercholesterolemia in which cells can’t use cholesterol.
What is the formula for calculating LDL?
Total CHOL - HDL - [TG/5]
What are HDL?
Lipoprotein synthesized in the liver which contains mostly proteins carrying mainly cholesterol
Why is HDL called good cholesterol?
Contains mostly proteins and is associated with decreased risk of atherosclerosis and coronary artery disease.
What is the function of HDL?
Lipid scavenger, returning cholesterol to liver to form cholic acid (component of bile)
From where do LDL take fats from and where do they take them to?
Transport fats from liver to tissue
From where do HDL take fats from and where do they take them to?
Transport fats from tissue to liver to be excreted
What is lipoprotein A.
It is lipoprotein that has LDL (APO-B100) with additional APO-A (carbohydrate rich)
What is the use of lipoprotein A?
It is more specific for assessing cholesterol concentration and heart disease risk than LDL. Independent risk factor
What do longtime elevations of lipids result to although it is initially symptomless?
Atherosclerosis
Xanthomas
What is the most common lipid disorder?
Hyperlipidemia
What can cause hyperlipidemia?
Diet Genetic inheritance Secondary to other issues like deficiency in hormones like insulin and thyroid hormone Prescribed drugs Alcohol intake Obesity
What causes high serum concentration of TG?
Dietary intake (non fasting specimen) Diabetes Hypothyroidism Pancreatitis Please LPL deficiency
What is plasma TG mostly determined by?
Lipoprotein lipase activity
What is LPL?
Is is the lipoprotein enzyme that is present in the tissues, released in vasculature and acts to hydrolyze TG from chylomicrons and VLDL, and utilize it by pulling it into cell for use
What enzyme pills TG into cells for use?
LPL
What does dysfunctional LPL result in?
An increase in TG levels but no increase in risk of atherosclerosis
What are symptoms of LPL deficiency?
Severe abdominal pain
Pancreatitis
Eruptive xanthomas
Lipids in retina
How common is familial hypercholesterolemia?
Common in 1 in 220 people
What causes FH?
Genetic defect of liver: inability to form cholic acid from cholesterol making it hard for cholesterol to be excreted in the bile
Genetic lack of apo-B receptors on cells: no LDL is made so no transportation of cholesterol from liver to tissue
What condition has a 20 times increased risk of developing early, aggressive heart disease?
FH
What condition equally causes an elevated cholesterol and TG in serum although the cause is unknown?
Nephrotic syndrome
What does apolipoprotein deficiencies result to?
Changed lipid fractions in the blood
APO A-1
Important component of HDL
HDL transport CHOL back to liver to be excreted
Deficiency of APO A-1 causes Tangier disease (excessive CHOL deposition in tissue)
APO B-100
Ligand for LDL receptor on cells
Helps to get LDL into cells for degradation
Deficiency leads the increased circulating LDL and hypercholesterolemia
APO C-11
In VLDL and chylomicrons
Activates LPL to breakdown chylomicrons
Deficiency increases TG concentration
What apolipoprotein induces lipoprotein lipase enzyme to breakdown TG?
APO C-11
APO E
Component of VLDL and LDL
Important for uptake of CHOL into cells, especially CNS cells
What disease are different alleles of APO E gene related to?
Alzheimer’s disease
Most APO E common genes associated with late onset of Alzheimer’s
APO E2 (least common, reduces risk of Alzheimer’s)
APO E3 (most common, doesn’t seem to affect risk of Alzheimer’s)
APO E4 (common, 15-25% of general population, increased risk of Alzheimer’s at early age, more when inherited from both parents, not a guaranteed determinant)
What causes hyperliproteinemia?
Increased synthesis in liver
Inappropriate breakdown
Why is high LDL bad?
Increased risk of atherosclerosis
Causes of hypolipoproteinemia
Genetic defects:
- Absent LDL, low cholesterol
- Low LDL
- Low HDL
- Tangier’s disease
