Lipids & Lipoproteins
-
Upload
tabletvoda -
Category
Documents
-
view
254 -
download
0
Transcript of Lipids & Lipoproteins
-
8/18/2019 Lipids & Lipoproteins
1/28
Lipids & Lipoproteins
-
8/18/2019 Lipids & Lipoproteins
2/28
2
• Lipids are a diverse group of compounds
that have many biological functions
• They have 2 primary purposes in living Organisms – Storage of excess caloreis
• Composed mostly of carbon hydrogen (rich source
of energy
– Structural role! "ntegral part of cell membrane
• #ecause of their uni$ue structural design
-
8/18/2019 Lipids & Lipoproteins
3/28
3
Lipids
• The term lipid applies to a class of compounds that aresoluble in organic solvents and nearly insoluble in%ater
• Some lipids contain non lipid groups (phosphoryl&amino& sulfate
• They are carried in the body by lipoproteins – Lipoproteins allo% fat to be dissolved into the plasma
• Subdivided into ' main groups based on their chemicalstructure
• atty acids• Cholesterol
• Triglycerides
• )hospholipids
-
8/18/2019 Lipids & Lipoproteins
4/28
4
Fatty Acids
• Linear chains of carbon and hydrogen
– Terminate in *COO+ carboxyl group
– Short chain , '*- carbons
– .edium , -*/2 carbons
– Long chain 0 /2 carbons
• 1iet is mostly long chains %ith even number
of carbons
-
8/18/2019 Lipids & Lipoproteins
5/28
5
Fatty Acids
• Saturated , no carbon double* bonds
• .onounsaturated 3 / C,Cdouble bond
• )olyunsaturated 3 0 2 C,Cdouble bonds
• C,C causes bend (4in4 inmolecule
– "ncreases space needed %hencompacted
– .ore fluid or li$uid 3 oils at roomtemp
Lauric acid (12:0)
α
β
ωOH
O
OH
O
Palmitoleic acid (16:1)
-
8/18/2019 Lipids & Lipoproteins
6/28
6
Clinical importance of fatty acids
• ecal fatty acids are sometimes measured todetect malabsorptive and pancreatic
disorders5the test is mostly consideredobsolete
• Serum free fatty acids help distinguish bet%een hyperinsulinemic hypoglycemia
( normal and disorders of fatty acidoxidation ( elevated and negative4etones
-
8/18/2019 Lipids & Lipoproteins
7/287
Triglycerides
• 6lycerol bac4bone %ith attached by ester bonds
• 7ach can be different
• Triglycerides %ith saturated (no 4in4s
– pac4 tightly 3 solid at room tempt
• Triglycerides %ith unsaturated typically oils at room temp
H
CH OH
C
C
H OH
H
H OH
Glycerol
H
CH O
C
C
H O
H
H O
CO
CO
CO (CH2)n
(CH2)n
(CH2)n
CH3
CH3
CH3
Triglyceride
-
8/18/2019 Lipids & Lipoproteins
8/288
Triglycerides
• .ost plant*derived are highlyunsaturated
– Corn& safflo%er& sunflo%er& and peanut oils• .ost animal*derived saturated
– 8sually solid at room temp
• Triglycerides 3 9o charged groups or polarhydrophilic groups – +ydrophobic
– 9ot soluble in %ater
-
8/18/2019 Lipids & Lipoproteins
9/289
Triglycerides
• Source of Triglycerides! – 7xogenous source! 1ietary
– 7ndogenous ! Liver and tissue storage
• Triglycerides transported by Chylomicrons(exogenous and :L1L (endogenous
• 7nergy source %hen plasma glucose is decreased
• Triglycerides catabolism is regulated by! – lipase&
– 7pinephrine&
– and cortisol
-
8/18/2019 Lipids & Lipoproteins
10/2810
Phospholipids
• Similar in structure totriglycerides
• T%o – usually /' * 2' C
long – One saturated; one unsaturated
• Third spot has phospholipidhead group
• Several types of phospholipid head groups – Choline& serine& ethanolamine&
inositol
-
8/18/2019 Lipids & Lipoproteins
11/2811
Phospholipids
• )hosphatidylcholine – +ave a choline head group
– .ost common in lipoproteins and cellmembranes
• )hospholipids are mphipathic lipidmolecules – +ydrophobic and hydrophilic head group
• "n Cell membrane
– )olar hydrophilic faces out%ard to%arda$ueous environment
– +ydrophobic face in%ard a%ay from%ater
http://science9.files.wordpress.com/2007/04/bilayer.jpg
-
8/18/2019 Lipids & Lipoproteins
12/2812
Cholesterol
• 8nsaturated steroid alcohol * amphipathic
• ' ring structures (& #& C& 1 %ith single side <
chain (li4e • +ydrophilic O+ on ring
• ' rings and side chain internal& O+ external
-
8/18/2019 Lipids & Lipoproteins
13/2813
Cholesterol
• )rimarily animal source
– )lants have other sterols
• Cholesterol not used as fuel source – 9ot readily cataboli=ed by cells
• Converted by liver to bile salts
– )romote fat absorption in bo%el
• Converted to steroid hormones
– :itamin 1>
• Transported by +1L and L1L
-
8/18/2019 Lipids & Lipoproteins
14/2814
Cholesteryl Ester
• +ydroxyl group bonded to
• Therefore no polar group 3 very
hydrophobic• 6enerally found in center of lipid droplets
%ith triglycerides
-
8/18/2019 Lipids & Lipoproteins
15/2815
Triglycerides &
cholesteryl esters
Lipoproteins
• Lipids need to be transported totissues and organs to performtheir metabolic functions
• Triglycerides ? cholesteryl estersare hydrophobic
• There should be a form ofhydrophilic compound
• Lipids are transported by a seriesof micelles called lipoproteins
-
8/18/2019 Lipids & Lipoproteins
16/28
-
8/18/2019 Lipids & Lipoproteins
17/2817
Lipoproteins
• Si=e correlates to lipid content
• Larger particles have more lipid core –
-
8/18/2019 Lipids & Lipoproteins
18/2818
Lipoproteins
-
8/18/2019 Lipids & Lipoproteins
19/2819
polipoproteins
• polipoproteins primarily on surface oflipoprotein particle
– .aintain structural integrity – recognition of cell surface receptors
– ctivators ? inhibitors of various en=ymes thatmodify lipoprotein particles
– mphipathic helix• +ydrophobic aa residues interact %ith lipids
• +ydrophilic aa resides interact %ith a$ueousenvironment
-
8/18/2019 Lipids & Lipoproteins
20/2820
Apolipoproteins
• po */• maAor protein of +1L
• po #• )rimary protein of L1L& :L1L and chylomicrons
• po C• Chylomicrons& :L1L& +1L
• po 7• L1L& :L1L& +1L
-
8/18/2019 Lipids & Lipoproteins
21/2821
Chylomicrons
• Contain apo #*'B lipoprotein
• Largest and least dense – up to /2@@nm
• Large si=e reflect light – post*prandialserum turbidity
• loat to the top – creamD layer
-
8/18/2019 Lipids & Lipoproteins
22/2822
Chylomicrons
• )roduced by intestine& %here
they are pac4aged %ith lipids
• Triglycerides and cholesterol
esters hydroly=ed by lipases• Leaves chylomicron remnant 3
liver recycled
• Therefore primary purpose istransport of dietary lipid to liver
and peripheral cells
-
8/18/2019 Lipids & Lipoproteins
23/2823
VLDL
• Contains apo #*/@@& apo 7& po C
•
-
8/18/2019 Lipids & Lipoproteins
24/2824
LDL
• Contain apo #*/@@ and apo 7
• .ore cholesterol rich
• orm from lipolysis of :L1L
• L1L ta4en up by cells through receptor
– )art of reason behind atherosclerosis
• 8p to B subclasses – still %or4ing on
diagnostic significance
-
8/18/2019 Lipids & Lipoproteins
25/2825
LDL
• Significantly smaller than :L1L – can
embed in vessel %alls
• Oxidi=ed& ta4en up by macrophages• .acrophages %ith too much lipid become
foam cells
• #ecome fatty strea4s – precursor ofatherosclerotic pla$ues
-
8/18/2019 Lipids & Lipoproteins
26/28
26
Lipoprotein (a)
• L1L*li4e molecule
• Contain apo (a lin4ed to apo #*/@@
• :ery heterogeneous number of peptidese$uences (4ringles in apo (a portion
• 7levated Lp (a increased ris4 for premature
coronary heart disease – Eringle regions homology %ith plasminogen
– Compete %ith binding – increase clotting
-
8/18/2019 Lipids & Lipoproteins
27/28
27
HDL
• Smallest and most dense
• Synthesi=ed by liver and intestine
• 1iscoidal +1L has 2 apo *" molecules – orms a ring around phospholipids ?
cholesterol
– 9ascentFne%ly secreted +1L – active inremoval of excess cholesterol from peripheral
cells
-
8/18/2019 Lipids & Lipoproteins
28/28
HDL
• 1iscoidal +1L ac$uires additional lipids&
cholesterol esters ? triglycerides form core
region , spherical +1L• Spherical +1L predominate in plasma
• +1L transport lipids bac4 to the liver from
peripheral tissues