ME04 - Lipid Transport and Storage Flashcards
A biochemical assembly that contains both proteins and lipids
Lipoprotein
Why are lipids are transported in the plasma as lipoproteins?
Because lipids are insoluble in an aqueous medium
Plasma lipids components
TAG, phospholipids, cholesterol, and cholesteryl esters (CE), and free fatty acids
Classification of lipoproteins
Chylomicrons, VLDL, IDL, LDL, HDL
Carry triacylglycerol & other dietary lipids from the intestines to the liver and to adipose tissue
Chylomicrons
Carry newly synthesized triacylglycerol from the liver to adipose tissue.
Very low density lipoproteins (VLDL), pre- b -lipoproteins
Intermediate between VLDL and LDL. They are not usually detectable in the blood.
Intermediate density lipoproteins(IDL)
Carry cholesterol from the liver to cells of the body. Sometimes referred to as the “bad cholesterol” lipoprotein.
Low density lipoproteins (LDL), b -lipoproteins
Collects cholesterol from the body’s tissues, and brings it back to the liver. Sometimes referred to as the “good cholesterol” lipoprotein.
High density lipoproteins (HDL), a- lipoproteins
Lipid-binding proteins which are the constituents of the plasma lipoproteins
Apolipoproteins
Characteristic of Apolipoproteins
The amphipathic (detergent-like) properties
Function of Apolipoproteins
Solubilize the hydrophobic lipid constituents of lipoproteins
Serve as enzyme co- factors, receptor ligands, and lipid transfer carriers
Corresponding Apolipoproteins with Lipoproteins
Chylomicrons B-48
VLDL, IDL, HDL B-100
METABOLISM OF CHYLOMICRONS
Chylomicrons are synthesized in intestinal cells
The TAG is from dietary lipid
Major apoprotein is Apo B-48
- Chylomicrons travel through the lymph into the blood
- Apo C II , the activator of lipoprotein lipase (an enzyme which hydrolyzes lipids in lipoproteins), and Apo E are transferred to nascent (newly synthesized) chylomicrons from HDL.
- Mature chylomicrons are then formed
- In peripheral tissues (adipose and muscle), TAG is digested by lipoprotein lipase
- Chylomicron remnants interact with liver receptors and are taken up by endocytosis
- Contents of remnants are degraded by lysosomal enzymes and the products (amino acids, fatty acids, glycerol, cholesterol) are reutilized
METABOLISM OF VLDL
- VLDL synthesized in liver after a high- carbohydrate meal
- VLDL formed from TAG that are packaged with Cholesterol, Apo proteins (esp. Apo B- 100 w/c is recognized by hepatic receptors), and phospholipids, and are released to the bloodstream
- In peripheral tissues (adipose, muscle), VLDL TAG are digested by lipoprotein lipase, and VLDL is converted to IDL
- IDL returns to the liver and is degraded
- IDL may also be degraded by lipoprotein lipase to LDL
- LDL reacts with receptors on various cells, is taken up by endocytosis in the liver, and is digested by lysosomal enzymes
METABOLISM OF HDL
HDL synthesized by liver and released into blood
- HDL cholesterol is converted to cholesteryl ester by LCAT (lecithin-cholesterol acyltransferase) which is activated by Apo A I
- A fatty acid from position 2 of lecithin forms an ester with the 3-hydroxyl group of cholesterol, producing lysolecithin and cholesterol ester
- As choleterol ester accumulates, HDL becomes spheroidal
- HDL particles are taken up by the liver and hydrolyzed
Major HDL protein
Apo A
Apolipoprotein that activates lipoprotein lipase
Apo C II - which is transferred by HDL to chylomicrons and VDL
Apolipoprotein that serves as recognition factor for cell surface receptors
Apo E
Apolipoproteins that are transferred back to HDL after TAG digestion
Apo C II and Apo E
Role of LIVER
(1) It facilitates the digestion and absorption of lipids by the production of bile, which contains cholesterol and bile salts synthesized within the liver de novo or from uptake of lipoprotein cholesterol
(2) It actively synthesizes and oxidizes fatty acids
(3) It synthesizes triacylglycerols and phospholipids
(4) It converts fatty acids to ketone bodies (ketogenesis)
(5) It plays an integral part in the synthesis and metabolism of plasma lipoproteins
Main storage area of triacylglycerol
Adipose Tissue - Cannot utilize glycerol to synthesize TAG, since it has no glycerol kinase
What factors stimulates and inhibits the main storage area of TAGs
Storage stimulated by insulin and nicotinic acid, PGE; and
Inhibited by glucagon, epinephrine, norepinephrine, thyroid hormone, growth hormone, and steroids
MOA of Caffeine on the storage of TAGs
Caffeine, which inhibits phosphodiesterase, stimulates lipolysis
Clinical Correlation on the Imbalance in the Rate of Triacylglycerol Formation & Export AND EXCESS USE OF ETHANOL
Fatty Liver»_space; Leads to Cirrhosis
Rationale why there is fatty liver result with imbalance in the rate of TAG formation and excess Ethanol
The NADH generated competes with reducing equivalents from other substrates, including fatty acids, for the respiratory chain, inhibiting their oxidation and causing increased esterification of fatty acids to form triacylglycerol, resulting in the fatty liver
How does alcohol competes with drug metabolism
Acetaldehyde is also dehydrogenated to acetate, which will be converted to acetyl CoA
Increased NADH also leads to lactate accumulation
An enzyme which becomes more active in chronic alcoholics.
cyt P450 enzyme called MEOS (microsomal ethanol oxidizing system) - utilizes NADPH and O2
Other causes of Fatty Liver
Malnutrition (lack of protein) Abetalipoproteinemia
Drugs and toxins
Types of adipose tissue that is present in many newborn or hibernating mammals as well as migratory birds
Its primary purpose is to generate body heat
Brown Adipose Tissue
Difference of Brown and White Adipose Tissue
White adipocytes (fat cells), which contain a single, large fat vacuole, brown adipocytes contain several smaller vacuoles and a much higher number of mitochondria
Brown fat also contains more capillaries since it has a greater need for oxygen than most tissues.
Effect of INSULIN on Lipid Transport
Reduce the release of free fatty acids into the bloodstream
Enhance glucose uptake into adipose tissues via the GLUT 4 transporter
Increases the activity of PDH and Acetyl CoA carboxylase, stimulating fat synthesis
Hormones that accelerate the release of free fatty acids from adipose tissue stores
Epinephrine, glucagon, ACTH, TSH, GH, and vasopressin
A newly discovered body weight regulatory hormone that stimulates lipolysis
Leptin
Lipid droplet-associated protein
Protein involved in the formation of lipid droplets in adipocytes
Perilipin
Function of Perilipin
Inhibits lipolysis by preventing access of lipases to the TAGs
With activation by protein kinase A, perilipins translocate away from the lipid droplet and allow hormone-sensitive lipase to hydrolyze the adipocyte triglycerides to release nonesterified fatty acids (NEFA).
Stimulates/Activates Perilipin
Protein Kinase A
SUMMARY
Cholesterol is produced mainly in the liver and intestine
Cholesterol and its esters are transported via lipoproteins
All the carbons of cholesterol come from Acetyl CoA
The TAG of the chylomicrons and VLDL are digested by lipoprotein lipase
LDL provides cholesterol to tissues
HDL picks up cholesterol from tissues
