Unit 3 - V. Lipoproteins Flashcards
Lipoprotein
- complexes of lipid and protein
- main function is to transport lipid through the bloodstream
- because lipid molecules are nonpolar/hydrophobic and the bloodstream is aqueous
apolipoprotein
- the protein component of a lipoprotein
- amphipathic property allows it to surround lipid and be water soluble
- 3 major classes: Apo-A, -B, - C
- 2 minor classes: Apo-D, -E
- Major role = receptor recognition
apo-A-I
- mostly found in HDL
- Function = major protein in HDL (75%); activates LCAT
apo-A-II
- mostly found in HDL
- function - 20% of protein in HDL; enhances lipase activity in liver
apo-B-100
- mostly found in LDL
- function: only protein component of LDL; binds to LDL receptor
Apolipoproteins in HDL
Apo-A-I
Apo-A-II
Apo-D
Apolipoproteins in LDL
Apo-B-100
Apolipoproteins in VLDL
Apo-C-I
Apo-C-II
Apo-C-III
Apolipoproteins in Chylomicron
Apo-A-IV
Apo-B-48
Apo-E
Apolipoproteins in IDL
Apo-E
Density of lipoprotein
- directly related to the percentage of protein in the molecule Highest Density - high protein, low fat HDL LDL VLDL Chylomicron Lowest Density = High fat, low protein
Chylomicrons (Chylo)
- 2% protein, 98% lipid
- predominant lipid = triglycerides
- assembled in endoplasmic reticulum of intestinal mucosal cells
- largest lipoprotein, lowest density
- function = transport dietary triglycerides, cholesterol, and cholesterol esters
- Lipoprotein lipase hydrolyzes triglyceride into glycerol + fatty acids. Fatty acids can attach to serum albumin to remain in circulation, stored in adipose tissue, or used as fuel by converting into ATP
Chylomicron remnant
- “leftover”, lipid component mostly consitists of cholesterol and cholesterol esters
- taken up by liver, mediated by receptors specific for apo-E
- lysosomal acid lipase hydrolyzes remnant
- cholesterol can be converted into bile salts, neutral sterol, VLDL or HDL
VLDL (Very low density lipoprotein)
- 10% protein, 90% lipid
- predominant lipid = triglycerides
- assembled in liver
- Function = transport triglycerides to adipose tissue for storage; transfer/exchange triglyceride with cholesterol esters in HDL to make LDL
- Remnant = IDL
IDL (Intermediate Density Lipoprotein)
- 12% protein, 88% lipid
- predominant lipid = cholesterol
- formed when VLDL indergoes hydrolysis
- Function = taken up by liver, mediated by receptors specific for apo-B and apo-E, to convert IDL into LDL
LDL (Low density lipoprotein)
- 25% protein, 75% lipid
- predominant lipid = half cholesterol
- majority synthesized in the liver
- protein component: 100% apo-B-100 one of the longest known polypeptide chains
- Function: Transport cholesterol to be incorporated into cell membranes of tissues or to synthesize various hormones
LDL subcategories
- LDL I, IIa, IIb = large = penetrate vascular endothelium = not associated with CAD
- LDL IIIa, IIIb, IVa, IVb = small = can penetrate endothelial cells = cause CAD (coronary artery disease)
LDL and Cardiovascular disease
- decrease in synthesis of LDL receptors due to saturated fatty acids or dysfunctional/absent LDL receptors
- genetic predispositions result in cholesterol not being removed from circulation or an increase in cholesterol synthesis by liver = raise LDL cholesterol
- accumulation of LDL cholesterol causes atherosclerosis (chronic inflammation of medium/large arteries)
- atherosclerosis is a common cause of coronary artery obstruction which leads to coronary artery disease (CAD), seen in Cardiovascular disease.
Statins
- used to treat hypercholesterolemia
- hypolipidemic agents, competitive inhibitors of HMG-CoA reductase (an enzyme that catalyzes a rate-limiting step in liver’s synthesis of cholesterol)
- reduces synthesis of cholesterol => increase production of LDL receptors => remove LDL from blood
Non modifiable risk factors of CAD
- advanced age
- male gender or women after menopause
- family history
Modifiable risk factors of CAD
- dyslipidemia
- hypertension
- cigarette smoking
- type 2 diabetes and insulin resistance
- obesity (central)
- sedentary life style
- atherogenic diet
HDL (high density lipoprotein)
- 55% protein, 45% lipid
- predominant lipid = phospholipid
- made in liver from chylomicrons and IDL
- function = cholesterol scavenger; LCAT helps esterify cholesterol into cholesterol esters
2 Fates of Cholesterol in HDL
- HDL taken up by liver where cholesterol is converted to bile acids/salts and secreted in bile to be removed from body (reduces risk of atherosclerosis)
- Cholesterol transferred to VLDL or LDL in exchange for triglyceride; catalyzed by CETP
Lipoprotein Lipase
- hydrolyzes triglycerides into glycerol and fatty acids
- used with chylomicrons, VLDL, and IDL
Lecithin Cholesterol acyltransferase
- LCAT
- catalyzes the esterification of cholesterol with fatty acid to made cholesterol ester
- in HDL
Cholesterol ester transfer protein
- CETP
- catalyzes the transfer of cholesterol from HDL to VLDL or LDL in exchange for triglyceride
Metabolic syndrome
- diagnosed with the presence of 3 out of 5 factors.
- treatment = pharmacological and nutritional therapy
Factors:
1. Elevated triglycerides
2. HDL cholesterol low
3. Abdominal obesity
4. Hypertension
5. Elevated fasting glucose
Determination of LDL
- can be measured (direct LDL) or calculated
Friedwald equation: LDL = total cholesterol - HDL - TG/5
*patient must be fasting - TG must be < 400