Lipids Flashcards
Triglycerides
The most abundant class of lipids. 5-25% of mammal body weight are lipids, 90% of those are fats (triacylglycerols)
Function:
energy storage (main)
thermal insulation
Where is fat stored?
Adipocytes
Why do fats provide so much energy?
Because they have long highly reduced carbon-hydrogen tails, which can easily become oxidized.
Carbohydrates for example are already bonded to oxygen so they are in a less reduced state. The energy cloud around CH is greater (around the C) than that of CO
Where does the energy of fat breakdown come from?
From oxidation of fatty acids. Fatty acid oxidation is the major energy source for many animal tissues.
where are the triglycerols that mammals use as fuel derived from?
1) the diet
2) de novo biosynthesis (in the liver)
3) storage depots in adipocytes
what is the major problem for digestion, absorption, and transport of dietary lipids?
Their lack of solubility in aqueous media.
Bile salts
1) bile acid (cholic acid + cation)
2) amphipathic (allows to water soluble enzymes to interact with the surface of micelles)
3) cholesterol derivatives
4) emulsify lipids and forms micelles
Dietary TAGs
1) They are hydrolyzed in the lumen of the small intestine
2) The products are absorbed by the intestinal mucosa and resynthesized into TAGs
3) Then they combine with proteins to form lipoproteins which solubilizes them allowing their transport
Di novo TAGs
1) Synthesized in the liver
2) Transported by VLDL
3) lipoprotein transported to peripherial tissue becomes hydrolyzed at inner surface of capillaries
4) The products of hydrolysis are either catabolized for energy or recombined into TAGs for storage
action of bile salts in emulsifying fats in the intestine
1) cholic acid ionizes and becomes a salt
2) salt is amphipathic and associates with TAGs and forms a micelle
3) micelle (with hydrophilic surface) associates with pancreatic lipase/colipase
4) hydrolytic action frees fatty acids to associate in a much smaller micelle, which is absorbed by the mucose.
lipoproteins
lipid-protein associate that transports lipids in the circulation, form non-covalent interactions, there is different ones
There is different types (with diff lipids+protein)
Common ground:
1) spherical shape
2) hydrophobic inner core made of cholesterol esters and TAGs
3) hydrophilic surface made of phospholipid head and free cholesterol
chylomicron
1) a type of lipoprotein that is produced in the intestinal villi by enterocytes
2) serves to transport dietary lipids 🙌 + dietary cholesterol in the circulation
3) Very low density
Types of lipoproteins
Classified based in density (the higher the lipid abundance, the lower the lipoprotein density):
1) chylomicrons
2) very low-density lipoprotein
3) intermediate-density lipoprotein
4) low-density lipoprotein
5) high-density lipoprotein
Apolipoproteins
1) Polypeptide component of lipoproteins
2) They have other roles
3) CII is the activator or lipoprotein lipase (hydrolyzes TAGs)
4) synthesized in the liver
pancreatic lipase/colipase
p.lipase: aids in intestinal digestion, carries reactions in oil-water interferance
Colipase: aids p.lipase in binding to the lipid surface
VLDL
1) transports TAGs that are synthesized in the liver
2) synthesizes in the liver
3) gets converted to IDL and LDL through the bloodstream
Lipoprotein lipase
1) hydrolyzes TAGs
2) activated by apolipoprotein is CII
3) serine esterase family (like trypsin) with active site Ser, His, and Asp
Family of lipoprotein lipase and pancreatic lipase
serine esterase family
Ser, His, and Asp form a catalytic triad
IDL
1) goes back to the liver
2) goes through lipo-protein lipase and form LDL
LDL
1) delivers cholesterol to cells in the body
2) synthesized in the liver -> from modification of VLDL
3) receptor mediated cholesterol transport
Excess cholesterol
after it is used, excess of cholesterol taken back to the liver by HDL
degradation of cholesterol
cholesterol cannot be metabolically degraded
Cholesterol esterification
Enzyme is LCAT (lecithin: cholesterol acyltransferase)
LCAT is secreted from liver to bloodstream, bound to HDL and LDL
Clathrin
1) major protein in coated pits
2) tiskelion structure, 36 of them
LDL receptors
synthesized on a need-base
ACAT
enzyme with the ability to esterify the cholesterol
Regulation of cholesterol
1) de novo cholesterol biosynthesis
2) formation and storage of cholesterol esters
3) LDL receptor density
exogenous pathway of transport of fat and cholesterol
1) diet chol travels through the chylomicron to the capillaries
2) remnant chylomicrons containing some cholesterol arrive at the liver
3) the liver repackages diet chol + di novo chol into VLDL
Endogenous pathway of transport of cholesterol
1) VLDL gets converted to IDL and HDL eventually through the bloodstream
atherosclerosis
excess cholesterol hardens in macrophages and make plaques, blocking blood vessels
what was the experiment to find receptor-mediated endocytosis?
cultured fibroblasts from familial hypercholesterolemia (FH) patients
coated pits
1) cell membrane pit that it is lined in its cytosolic side by clathrin
2) participated in receptor-mediated endocytosis
3) receptors are gathered into coated pits, which pinch off to become endocytic vesicles.
lipid droplet
Home for TAGs in adipocytes
Breaking down of TAGs enzymes
1) Adipose triacylgrlyceride lipase (ATGL)
2) Hormone Sensitive Lipase (HSL)
3) Monoacylglycerol lipase (MGL)
ATGL and HSL need to be phosphorylated to do their job
Adenylate cyclase
has the ability to cyclase AMP, cyclic AMP is a major molecule
Kinase
enzyme with the ability to do phosphorylation
LCAT
lecithin: cholesterol acyltransferase
1) esterifies cholesterol
2) binds to HDL and LDL
How is cholesterol taken up by the cells?
1) by LDL receptor in a receptor-mediated endocytocis
2) receptors are synthesized in ER, mature in the Golgi apparatus
3) they migrate to the cell surface, where they cluster in clarithin coated pits.
4) LDL binds to LDL receptors and both are internalized in endocytic vesicles.
5) several of these vesicles fuse and form an endosome
6) proton pumping in the endosome membrane drops pH and causes LDL to dissociate from its receptors.
7) Endosome fuses with lysosome and receptor bearing clarithin coat dissociates and return to membrane
8) LDL particles are degraded in the lysosome
9) cholesterol has different fates in the cell, LDL is hydrolyzed to amino acids
Where does the free cholesterol go after being released in the lysosome?
1) back to ER, where it is used for membrane synthesis
Regulation of intracellular cholesterol
1) reduces di novo syntehsis of cholesterol by inhibiting HMG-CoA reductase (also represses the transcription of the gene for hits enzyme)
2) Activates ACAT, making esterified cholesterols that promotes storage of excess into droplets of cholesterol esters
3) regulates synthesis of LDL receptor by decreasing transcription of the LDL receptor gene.
Oxidation of LDL and atherosclerosis
1) Accumulation of oxidized LDL in vessel walls triggers an inflammation response
2) white cells come and form macrophages that ingest cholesterol through scavenger receptors (unlimited)
3) cell becomes a cholesterol-engorded species (foam cells)
4) more white cells come to balance this and end up accumulating more cholesterol
5) the plaque is formed
HDL cholesterol or good cholesterol
1) It counteracts the LDL or “bad” cholesterol and atherosclerosis
2) Takes cholesterol back to the liver -> excretion
How is the release of fat from storage in adipocytes regulated?
Hormonally
Enzymes that participate in the hydrolysis of TAGs into glycerol and fatty acids
All are serine esterases
1) adipose triglyceride lipase (ATGL) (catalytic diad of Ser and Asp
2) hormone-sensitive lipase (HSL)
3) monoacylglycerol lipase (MGL)
Free fatty acids
When released from TAGs they exit the adipose cell by passive diffusion and bind to albumin in blood plasma
Glycerol after hydrolysis
Goes to bloodstream and is taken up by liver cells
Hormone regulation of lipolysis
1) Low blood glucose and energy need trigger the secretion of epinephrine and glucagon hormones
2) Activation of adenylate cyclase
3) Production of cAMP
4) Activation of cAMP-dependent protein kinase
5) Phosphorylation and activation of triacylglycerol lipase
6) Release of fatty acids in blood and binding of fatty acids to serum albumin. Transport of FA through serum albumin to the muscle tissues
7) B-oxidation of FA to produce acetyl CoA.
