These provide the transportation system for different types of water insoluble fatty substances
Lipoproteins
How are fats absorbed from diet and lipids synthesized by liver and adipose tissues, transported in the aqueous blood plasma?
associating non-polar lipids (triacylglycerol and cholesterol esters) with amhipathic lipids (phospholipids and cholesterol) and proteins to make water-miscible proteins
How do lipoproteins mediate the production of water-miscible lipoproteins?
They transport lipids from the intestine as chylomicrons and from the liver as very low density lipoproteins (VLDL) to most tissues for oxidation and to adipose tissue for storage.
What happens to excess calories in humans?
ingested in anabolic phase of feeding cycle followed by negative caloric balance when organism draws upon its carbohydrates and fat stores
How is lipid mobilized from adipose tissue?
as free fatty acid attached to serum albumin
What is the purpose of lipoproteins?
transport hydrophobic lipid (fat) molecules in water, as in blood or extracellular fluid
What specifically comprises lipoproteins?
single layer phospholipid and cholesterol outer shell
*with non-polar core and single surface layer of amphipathic lipids
What consists the lipophilic or hydrophobic portions of each molecule?
Triacylglycerol and cholesteryl ester surrounded by a single surface layer of amphipathic phospholipids and cholesterol molecules
Lipoproteins may be separated according to what?
electrophoretic properties (alpha (-), beta (-) and pre beta (-) lipoproteins
T or F: the density of a lipoprotein decreases as the proportion of lipid to protein increases
true
types of lipoproteins
chylomicrons
very high density lipoproteins
low density lipoproteins
HDL
lipoprotein which is the biggest and derived from intestinal absorption of triacylglycerol and other lipids
Chylomicrons
primary concentration of fat that travel to different tissues
Chylomicrons are responsible for transport of what
dietary tryiglycerides (exogenous) from the GI tract to liver to skeletal muscle and to adipose tissue
Composition of chylomicrons
Phospholipids
Cholesterol at core
Triglycerides (90-95%)
Protein (added by liver; if fats arent attached to proteins, lipoproteins should be increased like apolipoprotein B)
What happens after eating high fat food?
fat is emulsified by pancreatic lipase, increasing the surface area for absorption through the enterocyte.
*intestinal lining contains receptors that absorb the esterified fat afte which, it goes to the blood then most of it goes to the liver
[Synthesis of chylomicrons]
1. -2. Where are lipid components assembled?
SER and golgi apparatus of mucosal cells with apoproteins (B-48 and A-apolipoprotein) synhesized in RER
[Synthesis of chylomicrons]
3. The assembled lipid components are called?
nascent chylomicrons
*exocytosed into the lacteals of the intestinal villi; appear only after meals rich in fats
[Synthesis of chylomicrons]
4. How do nascent chylomicrons reach general circulation?
from lymph vessels (lacteals) via thoracic duct
[Synthesis of chylomicrons]
5. When are dietary lipids incorporated in chylomicrons?
following absorption in intestine
[Metabolism of chylomicrons]
1-2. What do the initial chylomicrons (synthesized by intestinal cells and only contain apoB-48 and apo A) acquire upon entering circulation?
apo C-II and apo E from plasma HDL to form mature chylomicrons
[Metabolism of chylomicrons] 3-4. T or F: apo E activates the enzyme lipoprotein lipase which causes hydrolysis of about 80-90% of the chylomicron triacylglycerols in the peripheral tissue such as muscles and adipose tissue
False, apo C-II
[Metabolism of chylomicrons]
5. What accompanies hydrolysis of chylomicron triacylglycerols?
transfer of most of the A and C-apolipoproteins to HDL.
*changes convert chylomicrons into smaller particles (chylomicron remnants)
[Metabolism of chylomicrons]
7. What happens to the fatty acids and glycerol released from the hydrolyzed triacylglycerols
FA: enter muscle and adipose tissue cells
Glycerol: enters the liver where it is used for synthesis of TAG
[Metabolism of chylomicrons] What happens to chylomicron remnants?
- removed from blood circulation by liver
- bind to lipoprotein receptors on surface of hepatocytes
- whole remnant particle is taken by hepatocyte via endocytosis
[Fate of chylomicron remnants] What happens to intracellularly endocytosed vesicles?
carried to lysosomes where they are degraded to release the constituents
T or F: Chylomicrons are usually present in plasma after fasting
False, removed from plasma within 6 hours by liver (inadequate clearance = creamy layer on plasma)
VLDLs are secreted directly into the blood of liver as?
nascent VLDL particle containing Apo B-100 which obtain Apo C-II and Apo E from circulating HDL
VLDLs are used in transporting what?
*50-65% = triglyceride
can be from excess dietary carbs converted in liver
endogenous triglycerides from liver to tissues for storage energy and newly synthesized triglycerides from liver to adipose tissue
These are also known as B-Lipoproteins and the most atherogenic lipoproteins which represents a final stage in catabolism of VLDL
*50% = cholesterol
LDLs
- transport cholesterol from liver to peripheral tissues
- synthesized in liver
- not in blood for long (need 12 hrs for test)
These lipoproteins are involved in VLDL and chylomicron metabolism and collect fat molecules from body’s cells/tissue to the liver
High Density Lipoproteins
- also synth in liver (but also in intestine)
- modulates VLDL in liver
T or F: HDLs work with VLDLS and LDLS to transport fat
false, VLDLs and chylomicrons
Why are HDLs considered as good cholesterol?
*30% phospholipids
20% cholesterol
50% apoprotein
→ More stable because it has more protein in membrane
→ Not easily absorbed in some parts of the body
→ Low triglyceride levels
Which apoproteins are good?
all except B (A, C others)
Key lipids in lipoproteins
→ Cholesterol
→ Triglycerides
→ Phospholipids (Serves as protection)
→ Glycolipids
Structure of the lipoprotein
→ Apoprotein
→ Cholesterol Esters (Found inside the lipoprotein)
→ Triacylglycerol (If LP is from liver)
→ Phospholipids
→ Free cholesterol
(creates closer interaction of the phospholipids and contributes to membrane stability)
pathway wherein transport of dietary lipids, mostly the chylomicron
transportation of triglycerides to the liver.
exogenous pathway
Transportation of lipids from the liver to the tissues (VLDL & LDL)
Endogenous Pathway
What is considered as high and normal triglyceride levels?
High: >=500 mg/dL
Normal: <= 150 mg/dL
[lipoprotein components] a glycerol with 3 attached fatty acids
triglyceride
*Exogenous source: Dietary
Endogenous source: Liver and Tissue storage
*95% of body fat (energy source)
hormones which regulate triglyceride catabolism
lipase, epinephrine, cortisol
tri> mono
lipoproteins which transport triglyceride
chylomicrons (exogenous)
VLDL (80% endogenous)
LDL (15% endogenous)
these are short to long chained molecules which compose triglycerides
fatty acids
Fatty acid which is SOLID at room temp
saturated fatty acids
*no double bond between carbons and from animal sources
Sources of unsaturated fatty acids
*with double bonds between carbons and usually liquid at room temp
plant sources (palmitoleic acid, oleic acid, myristoleic acid, linoleic acid, and arachidonic acid)
Why are most trans fatty acids bad?
synthetically made
without double bonds = blobs of fat
*some are good like palm oils
Optimal range of cholesterol
*component of membranes: steroid hormones, bile and vit. D
100-129 mg/dL
diseases which cause decrease in cholesterol below optimal levels
sphingomyelin problems
cerebrokinase deficiency
T or F: bacteria and plants do not synthesize cholesterol
true
plants have phytosterols which are good and lessen cholesterol absorbed in system
T or F: VLDL and chylomicrons transport cholesterol
false, HDL and LDL
These are used to determine fetal lung maturity from amniotic fluid
lecithin and sphingomyelin (phospholipids)
lipids with a carbohydrate content
glycolipids
*2/3 of glycolipids are distributed in intracellular membranes such as the golgi apparatus, endosomes, lysosomes, nuclear membrane, and mitochondria
•For cell to cell recognition and regulation
How do substrates recognize cell (ABO incompatibility)
glycolipid moiety attached to phospholipid head
*used in signaling
these are outer protein “shell” of lipoprotein molecule which binds together lipids for transport
apolipoprotein (B, C, E)
biggest alipoprotein and primarily composes the VLDL
Apo B-100 (synthesized in the liver)
*one of the longst single polypeptide chains known
truncated form of apo B synthesized in intestine which chylomicrons contain
B-48
*forme from same mRNA as B-100 after introduction of a stop signal by an RNA editing enzyme
These are smaller polypeptides freely transferable between several different lipoproteins
Apo C-1, C-II, and C-III
These are found in VLDL, HDL, chylomicrons, and chylomicron remnants
Apo-E
*accounts for 5-10% of total VLDL apolipoproteins in normal subjects
What disease is influenced by different alleles of Apo E?
Alzheimer’s Disease (Dementia)
What is Apo E responsible for?
- Mainly produced by astrocytes
- Transports cholesterol to neurons via Apo E receptor
interactions with cell membranes and enzymes to transport lipids to specific locations
(with role in immunity)
apolipoprotein which is a cofactor of enzymes
→ Apo-AII and Apo-C-II for Lipoprotein Lipase
→ Apo-A-I for Lecithtin cholesterol acyl transferase or enzyme inhibitors
→ Apo C-I for cholesteryl ester transfer proteins
apolipoprotein which is part of structure of lipoproteins
apo B
Other functions of apolipoproteins
Ligands for interaction with lipoprotein receptors in tissues
→ ApoB-100 and apo E for the LDL receptors
→ apo E for the LDL receptor– related protein (LRP) which has been identified as the remnant receptor,
→ Apo A-1 for the HDL receptor.
This is believed to be an important factor in human neuordegenerative disorders
Apo D
apoprotein for activation of LPL
Apo C-II
apoprotein which is a major structural protein of HDL and activator of LCAT
Apo A-1
apoprotein which modulates hepatic uptake of VLDL and IDL
Apo C-1
apoprotein which aids in secretion of VLDL from liver, a structural protein of VLDL, IDL and HDL and a ligand for LDLR
Apo B-100
apoprotein which is an inhibitor of LPL activity
Apo C-III
apoprotein which is a ligand for binding of IDL and remnants to LDLR and LRP
Apo E
apoprotein aids in secretion of chylomicrons from intestine
Apo B-48
effects of insulin
→ Always decreases plasma glucose
→ Inactivates lipase (Decreases lipolysis and the catabolism of triglycerides to fatty acids or glucose)
→ Stimulates lipogenesis (Involved in the conversion of fatty acid to triglycerides)
→ Allows transport of fat to the hepatocytes
→ Increase efficiency of gluconeogenesis
What happens with insulin deficiency in DM cases?
insulin deficiency promotes the release of fatty acids via lipolysis of triglycerides by the liver (lose weight)
Why are laboratory measurements of lipoproteins important?
association with coronary artery disease
How many hours should a patient fast for total cholesterol and triglyceride testing?
at least 12 hours
What enzymes do most methodologies in triglyceride testing use?
those that break glycerol from its fatty acids since triglyceride cannot be measured directly
How is HDL testing done?
Dextran sulfate, a precipitating agent, is added to patient’s plasma wherein non-HDL is precipitated and centrifuged to bottom leaving supernatant to contain HDL to be measured via total cholesterol method.
What can interfere with HDL testing?
Elevated triglycerides (>400mg/dL) may interfere with the separation of non- HDL (lower HDL)
What equation is used to calculate LDL since direct measurement is uncommon?
Friedewald calculation
→ 𝑳𝑫𝑳 − 𝑪 = 𝑻𝒐𝒕𝒂𝒍 𝑪𝒉𝒐𝒍𝒆𝒔𝒕𝒆𝒓𝒐𝒍 − 𝑯𝑫𝑳 − 𝑻𝒓𝒊𝒈𝒍𝒚𝒄𝒆𝒓𝒊𝒅𝒆𝒔/ 𝟓
→ Example: Cholesterol= 200; HDL= 35; Triglyceride= 200
LDL= 125 mg/dl
cholesterol deposits in coronary arteries occlude blood flow
arteriosclerosis
*heart (CAD)
arms/legs (PVD)
brain (CVD)
conditions associated with plaque formation in Arteriosclerosis
→Increased plasma cholesterol
− Can also accompany increase in HDL if healthy diet is observed with fatty diet
→ Increased plasma LDL
→Decreased plasma HDL
(see target ranges by NECP and other risk factors for CAD)
(see target ranges by NECP and other risk factors for CAD)
plasma is placed inside the donut where lipids spin to the outside of donut
ultracentrifuge
