Lipids serve many important functions in the body. They are the most efficient form for storing energy, providing 9 kcal/g compared to carbohydrates' 4 kcal/g. Lipids also insulate and protect internal organs. The body can obtain lipids through biosynthesis, diet, or limited synthesis of unsaturated fatty acids. Triglycerides are the main form for storing fat and energy in the body. They are broken down into fatty acids and glycerol during lipolysis to provide energy. Cholesterol and other lipids are transported through the body by lipoproteins like chylomicrons and HDL.
3. Lipids
• like CHO, lipids are composed of carbon, hydrogen and
oxygen
• unlike, CHO they do not contain multiple hydroxyl
groups for hydrogen bonding, and therefore are insoluble
in water
• Lipids include a large variety of molecules:
- fatty acids
- triglycerides
- waxes
- eicosanoids
- steroids
- fat soluble vitamins
5. • insoluble in water
• wide range of functions: insulate and protect internal organs, signaling molecules, energy
• most efficient form in which energy is stored in the body
• fats in animals absorb and sequester nonpolar contaminants, such as DDT, PCBs,
organomercury
•excess glucose, lipids and proteins are stored in adipose cells
General info on Lipids…
6. Lipids: diverse class of molecules
1) Energy and storage – fatty acids,
triacylglycerides, waxes
2) Membrane structure – phospholipids,
glycolypids, sterols
3) Signaling, cofactors and pigments –
Eicosanoids, sterols, fat soluble vitamins
8. Triglycerides
• The lower melting points of triglycerides rich in
unsaturated fatty acids are related to differences in
their three-dimensional shape.
– Hydrocarbon chains of saturated fatty acids can lie
parallel with strong London dispersion forces between
their chains; they pack into well-ordered forms and
melt above room temperature
– Because of the cis configuration of the double bonds in
unsaturated fatty acids, their hydrocarbon chains have
a less ordered structure and London dispersion forces
between them are weaker; these triglycerides have
melting points below room temperature.
10. 10
Properties of Triglycerides
• Highly reduced hydrocarbons
• Insoluble in water
• Segregated into lipid droplets
• Good storage properties make them difficult as fuels
– Must be emulsified before digestion
– Must have special transport in the blood
– The relative stability of the C-C bond must be
overcome
• 3 sources: diet, adipose tissue, and synthesis from
carbohydrates
11. Emulsification
• Fats are not water soluble
• Made soluble by bile salts (amphipathic) that
are made in the liver and stored in the gall
bladder
• Converted to mixed micelles of bile salts and
triacylglycerols
12. Bile Salts
• Bile salts, the oxidation products of cholesterol.
– synthesized in the liver, stored in the gallbladder, and
secreted into the intestine where they emulsify dietary
fats and aid in their absorption and digestion
13. Fat digestion and Absorption
https://www.youtube.com/watch?v=O1XToe78zxs
14. Packaging for transport
• Converts triacylglycerols to monoacylglycerols and
diacylglycerols, fatty acids, and glycerol
• Diffuse into epithelial cells lining intestine
• Converted back to triacylglycerols and packaged with
cholesterol and proteins into chylomicrons
• Contain apolipoprotein C-II for recognition
• Travel into lymphatics and then blood to target
15. 15
What does a chylomicron look like?
Lipoprotein particles
classified by density:
Chylomicrons / VLDL
/ LDL / IDL/ HDL
Proteins recognized
by cell surface
receptors
ApoCII binds LPL in
adipose tissue and
skeletal muscle
lipid-binding proteins
in the blood
16. Chylomicrons
• assembled in intestinal mucosa, carry exogenous fats and
cholesterol via lymph system to large body veins
• Adhere to inner surface of capillaries in myocytes and adipocytes
• Fats contained within (not cholesterol) are hydrolyzed by
lipoprotein lipase, freeing fatty acids and monoacylglycerols
• The remaining structure is called a chylomicron remnant, which
contains cholesterol
• Remnant reenters circulation system where it is taken up by liver
• Thus, chylomicrons deliver dietary fats to muscle and adipose tissue
and cholesterol to liver.
20. Apoproteins or apolipoproteins
• protein components of lipoproteins
• proteins, though water soluble, have a hydrophobic and a
hydrophilic character that is apparent in their alpha helices
• Their alpha helical regions are stabilized upon incorporation
into lipoproteins
• There are 10 apoproteins common in humans
21. VLDL, IDL, and LDL are interrelated
• VLDL- Excess FA and glucose is converted into
hepatic TG and transported as VLDL to muscle
and adipose
-like chylomicrons, VLDL are degraded by LPL
• IDL and LDL appear in the circulation as VLDL
remnants.
– After unloading TG, VLDL is converted to LDL by removal of all
proteins except apo B-100 and esterification of most of the
cholesterol by lecithin-cholesterol acyl transferase (LCAT)
associated with HDLs.
22. HDL Transports Cholesterol from
Tissues to the Liver
• removes cholesterol from tissues and transports it to
the liver.
• HDL is created mostly from components from other
degraded lipoproteins.
• HDL converts cholesterol to cholesteryl esters by LCAT,
an enzyme activated by apoA-I in HDL.
• HDL appears to get cholesterol to the liver
1) by transfer of the cholesteryl ester to VLDL which
after degradation to IDL and LDL is taken to the liver
2) by direct interactions between HDL and the liver via
a specific HDL receptor.
• The liver disposes of cholesterol as bile acids.
• also called "good cholesterol" because it is associated
with lowering cholesterol levels.
26. Cholesterol
• Cholesterol is the most abundant steroid in the
human body, and also the most important.
– It is a component in plasma membranes in all animal
cells.
– It is the precursor of all steroid hormones and bile
acids.
27. Cholesterol uptake
• Cholesterol makes it to
animal cell membranes by
either external transfer,
or by cellular synthesis
• Exogenous cholesterol
reaches cells from LDL
• LDL binds to LDL
receptors, which are
transmembrane proteins
that bind both ApoB-100
and apoE
• The receptors form
clusters of “coated pits”
28. Receptor mediated
endocytosis
• Clathrin, the scaffolding protein of
the coated vesicles, forms the
backing of the coated pits.
• The pits invaginate into the plasma
membrane forming coated vesicles
that fuse with the lysosomes
• The lysosomes hydrolyze the
cholesteryl esters, yielding free
cholesterol
• This cholesterol can be
incorporated into cell membranes
or reesterified for storage
• Interestingly, high intracellular
cholesterol suppresses synthesis of
LDL receptor and biosynthesis of
cholesterol
29. Steroids
• Steroids: a group of plant and animal lipids that
have this tetracyclic ring structure.
30. Steroids
• cholesterol, bile acids,
vitamin D, and many
hormones
• Oxidized sterols
• Lipid soluble and
enter cells
• Bind nuclear
receptors and alter
gene expression
and metabolism
32. Role of Hormones
• Can mobilize fats from adipose
• Release as Fatty acids
• Epinephrine and glucagon secreted in
response to low glucose activates the of
release cAMP
33. 33
Mobilization of Stored Triglycerides
• Epinephrine and
glucagon initiate
lipolysis
• Fat droplets in adipose
coated with perilipins –
proteins that restrict
access to lipid droplets
• cAMP-dependent PKA
phosphorylates
perilipin, causing
activation of lipase
• What is the fate of the
glycerol backbone?
34. 34
Glycerol Oxidation
95% of the energy in a fatty acid is derived
from the oxidation of acetyl-CoA
5% from glycerol
35. Animation of Process
• http://www.wiley.com/legacy/college/boyer/0
470003790/animations/fatty_acid_metabolis
m/fatty_acid_metabolism.htm
36. Fatty Acids and Energy
• Fatty acids in triglycerides are the principal
storage form of energy for most organisms.
– Hydrocarbon chains are a highly reduced form of
carbon.
– The energy yield per gram of fatty acid oxidized is
greater than that per gram of carbohydrate
oxidized.
38. More on Lipids……
• fats insulate and protect internal organs
• most efficient form in which energy is stored in the
body
-9 kcal/ gram as opposed to 4
• fats in animals absorb and sequester nonpolar
contaminants, such as DDT, PCBs, organomercury
• excess glucose, lipids and proteins are stored in
adipose cells