Lipids, lipoproteins, and lipid trafficking week 2 Flashcards
What are 8 classes of lipids found in the human body? List expamples.
What 2 classes of lipids are typically synthesized for energy and storage?
- Fatty acids: R-COOH, where R is a hydrocarbon chain, which can be saturated or unsaturated (have 1-5 double bonds); short, medium, long or very-long chain; and branched or unbranched
- Triglycerides (triacylglycerols): esters of 3 fatty acids and glycerol
- Phosphoglycerides (phospholipids): esters of glycerol with 2 fatty acids and a phosphate-containing group
a. phosphatidylcholine (lecithine)
b. phosphatidylethanolamine
c. phosphatidylserine
d. phosphatidylinositol
e. lysophosphatidylglycerides
(glycerol+1 fatty acid+1 P-cont. comp.)
f. cardiolipin
g. plasmalogen - Sphingolipids (sphingosine-containing lipids)
a. sphingomyelins
b. glycolipids
cerebrosides
globosides
gangliosides
sulfatides - Steroids (containing a sterol ring)
a. cholesterol
b. bile acids/salts
c. steroid hormones - Fat-soluble vitamins
a. vitamin A
b. vitamin D
c. vitamin E
d. vitamin K - Eicosanoids
a. prostaglandins
b. thromboxanes
c. leukotrienes - Ketone bodies are short lipids that are produced during fasting
FA and triglycerides are mostly synthesized for energy and storage. Other types of lipids are synthesized for other purposes.
Lipids are usually defined as being nonpolar or hydrophobic, although most of them are amphipathic. What are examples of each type of lipid.
Most lipids contain what type of lipid?
How are most FA stored?
Lipids are usually defined as being nonpolar or hydrophobic, although most of them are amphipatic (i.e. they have both hydrophilic and hydrophobic properties).
Some of the lipids, such as triacylglycerols and cholesterol esters are totally hydrophobic. Phosphoglycerides are good examples of amphipatic lipids.
Most lipids contain fatty acids. Most fatty acids are stored as triacylglycerols.
List some functions of lipids.
What 3 sources do we obtain lipids from? (external and internal)
What kinds of lipids are produced by each of these sources?
Dietary: triacylglycerol, short- and medium chain fatty acids, cholesterol ester, phospholipids, lipid-soluble vitamins
Synthesized by liver: triacylglycerols, cholesterol, bile acids and salts, phospholipids, ketone bodies-only made in the liver. Note that cholesterol synthesized by the liver is shared with the body while cholesterol synthesized by other organs (sex organs for example) is not shared.
Synthesized by some other cells: phospholipids, eicosanoids, cholesterol derivatives (examples: immune cells, specialized glads, etc)
The majority of dietary fat is composed of what 4 types of lipids?
- TGs
- phospholipids
- cholesterol
- cholesterol esters
Digestion of fat begins in the stomach with what enzymes? What kind of fat do they digest?
In what people are these enzymes important?
Where does emulsification of lipids happen? What facilitates emulsification of lipids?
Digestion starts in the stomach where acid –stable lipases (both of lingual and gastric origin) digest those TAGs that have short or medium FA side chains (mainly found in milk; important in neonates-ready made energy source, and those individuals with pancreatic insufficiency).
Emulsification of lipids occurs in the small intestine by bile salts and by peristalsis. Bile salts act like detergents to solubilize the fatty acids and monoglycerides, cholesterol, dietary lysophospholipids and fat-soluble vitamins and form mixed micelles.
What type of lipid does pancreatic lipase digest? What are the products of its digestion?
What protein is needed for pancreatic lipase to perform its job? What is the role of this protein?
The important enzyme in the digestion of triglycerides is pancreatic lipase. This enzyme is anchored to the surface of fat droplets by a pancreatic protein called colipase, and cleaves two fatty acids from each triglyceride to yield 2-monoglycerides.
What types of lipids does cholesterol esterase digest?
What types of lipids does phospholipase A2 digest? What is the product of its digestion?
What does lysophospholipase digest? What is the product of its digestion?
- To digest cholesterol esters, the pancreatic juice contains a specific cholesterol esterase, which acts on cholesterol esters, monoglycerides and other lipid esters.
- To digest phospholipids, the pancreatic juice also contains phospholipase A2, which cleaves off one fatty acid producing lysophospholipids, which are then further digested by lysophospholipase to cleave off the other fatty acid.
Micelles transport digested lipids to the surface of enterocytes.
What types of lipids are found in micelles?
What happens to the micelle at the surface of enterocytes?
By what process do lipids enter enterocytes?
The micelles transport these lipids (2-monoacylglycerol, cholesterol and glycerylphosphoryl base) to the surface of the enterocytes where the micelles disaggregate and lipids enter the cells mainly by passive diffusion.
How is the absorption of long chain FA enhanced?
How is the absortion of cholesterol enhanced?
Why do we only absorb 30-40% of dietary cholesterol?
Where are bile salts reabsored? Where do they go?
- Absorption of long-chain fatty acids is enhanced by a transporter (FATP4) and that of cholesterol by a channel (NPC1L1). However, sterols can be pumped out of the cells by an ABC transporter, thus only 30-40% of cholesterol is absorbed.
- The bile salts are reabsorbed in the small intestine by the level of the ileum, return to liver and participate in cycles of micelle formation before being absorbed.
After absorption of FA and cholesterol, what processing occurs in enterocytes?
How are they delivered to the body?
How are FA shorter than 10-12 carbons absorbed? (where do they go, how are they released to the body)
- In the ER of the mucosal cells, triglycerides areresynthesized from the fatty acids (only > 10-12 carbon) and cholesterol is re-esterified with fatty acids. The triglycerides, cholesterol esters and phospholipids are packaged in lipoprotein particles, so-called chylomicrons, for delivery to the lymphatic system and throughthe thoracic duct, enter the systemic venous system. They are delivered to the peripheral tisues (adipose, muscle) then the chylomicron remnants are taken up by the liver.
- However, fatty acids that are shorter than 10-12 carbons pass the enterocytes and are released to the hepatic portal vein, feed into the liver and then can enter the general circulation where they bind to albumin.
What are the functions of secretin and cholecystokinin?
- Secretion of enzymes by the pancreas is stimulated by food intake and two hormones, secretin and cholecystokinin.
- Secretin, produced by endocrine cells of the duodenal wall, stimulates bicarbonate secretion by ductule epithelial cells of the pancreas.
- Cholecystokinin, also released by endocrine cells of the duodenum, acts on acinar cells of the pancreas to stimulate digestive enzyme secretion and causes the gallbladder to contract and deliver bile into the duct.
What are fat absorption/digestion disorders called? What do they result in? What are causes of this disorder?
Fat absorption/digestion disorders are called steatorrhea. It results in increasing lipid in the feces. It can be the result of disturbance in lipid digestion and/or absorption, such as:
problem with bile salt synthesis/secretion (liver/gallbladder issue)
pancreatic problems (exocrine pancreas issue)
defective absorption by enterocytes
Examples are cystic fibrosis (poor digestion) or shortened bowel, Celiac disease (decreased absorption).
also, hormonal issues can cause steatorrhea.
see pg 154 of notes
What are the 3 types of substances used as vehicles to transport lipids? If applicable, state what kind of lipids these vehicles transport and where these lipids come from.
(1) plasma lipoproteins in which triacylglycerols and cholesterol esters are carried in protein and phosphoglyceride -coated lipid droplets
(2) fatty acids bound to serum albumin (derived from adipose storage or short- and medium chain fatty acids from diet)
(3) ketone bodies, acetoacetate and beta-hydroxybutyrate, formed by liver and used by different cells.
Where are lipoproteins synthesized?
What are lipoproteins composed of? What is the inner and outer layers?
What are 2 fxns of lipoproteins?
What is significant about the membrane of lipoproteins? (hint: 2 things)
Plasma lipoproteins are synthesized in both intestine and liver and are a heterogeneous group of lipid-protein complexes composed of various types of lipids and apoproteins. They carry lipids in blood, to and from different tissues.
Hydrophilic outer layer: apoproteins, phosholipids, cholesterol)
Hydrophobic inner nucleus: triacylglycerol, cholesterol ester, fat-soluble vitamins
Note that unesterified cholesterol is in the membrane of lipoproteins (bc it has a polar hydroxyl group) and esterified cholesterol (completely apolar) is found within the core of lipoproteins. Also, note that the membrane is a monolayer of phospholipids. The core is completely apolar but the surface needs to be polar to be soluble in the aqueous blood.
List the lipoproteins from largest to smallest.
What apoproteins are contained within each type of lipoprotein?
State the source of each type of lipoprotein.
What are the main compositions of each type of lipoprotein?
slide 16 of notes
Explain the steps involved in chylomicron metabolism.
What apoproteins are involved? What is the signficace of these apoproteins?
What enzyme is involved? What hormone stimulates its synthesis? What is the significance of the Km of this enzyme in the heart and adipose tissue?
- Chylomicron is assembled in the intestine (apo B-48, phospholipids, cholesterol, cholesterol ester and lots of triglycerides), excreted to the lymphatics then to the blood.
- Apo C-II and Apo E are transferred to the surface of the chylomicron from HDL. These apoproteins are important for the recognition of chylomicrons by cells, releasing of its contents, and recognition of chylomicron remnants by the liver.
- On tissue surfaces, lipoprotein lipase is activated by Apo C-II and hydrolyzes TGs to glycerol and fatty acids, the latter are taken up by the tissues (a lot by adipose). Glycerol is released to the liver and used for gluconeogenesis. Lipoprotein lipase synthesis is stimulated by insulin, thus more fatty acids can be taken up after we eat. LP has low Km in the heart and high Km in the adipose tissue (heart can take up FA any time).
- Chylomicron remnant now is rich in cholesterol and cholesterol ester, loses Apo C-II to HDL and delivers cholesterol to liver. Liver recognizes Apo E and takes up chylomicron remnants by receptor mediated endocytosis.
Explain VLDL (and LDL) metabolism. Describe the apoporteins involved.
- VLDL is assembled in the liver (apo B-100, phospholipids, cholesterol cholesterol ester and lots of triglycerides), and secreted to the blood.
- Apo C-II and Apo E are transferred to the surface of the VLDL from HDL.
- On tissue surface, lipoprotein lipase is activated by Apo C-II and hydrolyzes TGs to glycerol and fatty acids; the latter are taken up by the tissues (a lot by adipose).
- LDL is formed, which is rich in cholesterol and cholesterol ester. Apo C-II and Apo E are given back to HDL, and LDL binds to liver and extrahepatic tissues through Apo B-100, delivering cholesterol to both.
Explain the metabolism of HDLs.
What apoporteins are involved?
What enzyme is found in HDLs that is critical for their fxn?
Explain the interaction btwn HDLs and another specific lipoprotein. What enzyme is involved in this? What is the purpose of this interaction?
- HDL is assembled in the liver and intestine (contains mainly phospholipids and apoproteins A, C and E), and secreted to the blood.
- It serves as a reservoir for Apo C-II and Apo E that are transferred to the surface of the VLDL and chylomicron particles from HDL.
- HDL has high affinity for cholesterol; it can take up cholesterol from the cell membranes of peripheral tissues and from other lipoproteins. Cholesterol is immediately esterified by LCAT (lecithin:cholesterol acyltranferase), which is synthesized by the liver and _activated by Apo A-1 (_other name is PCAT – phosphatidylcholin: cholesterol acyltranferase). If too much unesterified cholesterol was incorporated into HDL membranes, they would be very rigid. LCAT increases the capacity of HDLs to carry cholesterol.
- HDL carries this cholesterol to steroidogenic tissues and to liver, taken up by a scavenger receptor (SR-B1). HDL , through ApoA1, binds to its own receptor. regardless of other lipoproteins circulating (VLDLs, LDLs, chylomicrons), HDL will be taken up by the liver because it does not have to compete. Picking up cholesterol and delivering it to liver makes HDL a “good” cholesterol carrier. The LCAT-HDL system protects cells, especially their plasma membrane, from the effects of excessive free cholesterol.
- There is also an exchange reaction between HDL and VLDL, VLDL gives TG while HDL gives cholesterol and cholesterol ester. This process is performed through CETP (cholesterol esterase tranferase protein). Cholesterol is expensive to synthesize. If not enough choesterol as incorportaed into VLDLs by the liver, it can gain extra cholesterol through this mechanism.
Through what receptor are LDLs, VLDL remants (IDL) and chylomicron remnants take up by the liver?
What happens to these lipoproteins (as it pertains to cholesterol) once in the liver?
What 3 things may cholesterol be used for (outside of composition of lipoproteins) once within the liver?
What 2 things does cholesterol have negative feedback on? What is the significance of this?
How is cholesterol stored? What enzyme is responsible for this?
- LDL, VLDL remnant (IDL) and chylomicron remnant particles are taken up by the liver through a specific apo B-100/apo E receptor (LDL receptor).
- In the cells, cholesterol is separated from the rest of the lipoprotein by lysosomal degradation (FA are taken off of cholesterol if they are esterified but cholesterol itself cannot be degraded).
- Cholesterol is used for synthesizing cholesterol derivatives (steroid hormones) in steroidogenic tissues.
- Cholesterol is eliminated by the liver (through bile). Cholesterol has a feed-back effect on its own synthesis and it downregulates the synthesis of the LDL receptor. If cholesterol accumulates within the liver cell, the LDL receptors willnot be recycled to the membrane and lipoproteins that use this receptor stay in the blood.
- Cholesterol can be secreted in the form of bile acids, can be used for hormone synthesis and can be stored in esterified form in the cell. The enzyme is ACAT (acyl CoA:cholesterol acyltransferase). Note that this storage is not very large and is only temporary.
Explain the causes of the following diseases and related disorders if applicable.
Hepatic steatosis
Type I hyperlipoproteinemia
Type II hyperlipidemia
Familial type III hyperlipoproteinemia
Familial LCAT deficiency
- Hepatic steatosis (fatty liver) – imbalance between hepatic triacylglycerol synthesis and VLDL secretion. TG synthesis is not regulated very well or the liver has decreased capacity to synthesize apoproteins (and form VLDLs). Obesity, uncontrolled diabetes mellitus, chronic alcoholism can trigger this.
- Type I hyperlipoproteinemia – lipoprotein lipase deficiency, dramatic upregulation of chylomicrons in the blood (hypertriglycerolemia)
- Type II hyperlipidemia – (familial hypercholesterolemia) LDL receptor deficiency, LDL cannot clear from blood. Hypercholesterolemia and premature atherosclerosis develops.
- Familial type III hyperlipoproteinemia – apolipoprotein E problem, deficiency in the clearance of chylomicron remnants. Hypercholesterolemia and premature atherosclerosis develops.
- Familial LCAT deficiency – absence of LCAT results in marked decrease of HDL. This disorder is not as serious because cholesterol can still go into membrane of HDLs and be recycled (just not as much)
