Download - Lipids & Lipoproteins

8/18/2019 Lipids & Lipoproteins

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Lipids & Lipoproteins


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• 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


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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


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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


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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)


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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


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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


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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


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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


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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


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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


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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


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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


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Cholesteryl Ester

• +ydroxyl group bonded to

• Therefore no polar group 3 very

hydrophobic• 6enerally found in center of lipid droplets

%ith triglycerides


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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


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Lipoproteins

• Si=e correlates to lipid content

• Larger particles have more lipid core –


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Lipoproteins


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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


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Apolipoproteins

• po */• maAor protein of +1L

• po #• )rimary protein of L1L& :L1L and chylomicrons

• po C• Chylomicrons& :L1L& +1L

• po 7• L1L& :L1L& +1L


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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


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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


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VLDL

• Contains apo #*/@@& apo 7& po C

•


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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


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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


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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


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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


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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