2.METABOLISME LIPID (prf.frans).pptx

8/18/2019 2.METABOLISME LIPID (prf.frans).pptx

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METABOLISME LIPID

BAGIAN BIOKIMIA dan BIOLOGI MOLEKULERFAKULTAS KEDOKTERAN

UNIVERSITAS TARUMANAGARA

F. Ferdinal


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Definisi Lipid

• Kelompok senyawa yang secara kimia he erogen! akane api secara fisika memiliki sa " sifa #ersama! yai "

rela if idak lar" dalam air dan lar" dalam pelar" polar$organik%! seper i e anol! kloroform! e er! dll&

• Komponen s r"k "r #iomem#ran' fosfolipid! koles erol• Simpanan ener(i 'TA)• *eg"la or me a#olik' hormon s eroid! Eicosanoids

• +ell"lar recogni ion' )angliosida

• Mem#an " a#sorpsi ,a Sol"#le -i amins• Pro eksi organ in erna• Thermal . Elec ric ins"la or • Shape . +on o"r #ody• Tas e . Pala a#lli y

,"ngsi Lipid


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Klasifikasi LipidI& Simple Lipids! es er dari ,A dengan #er#agai alkohol

/& TA) $fa s% 0 es er dari ,A dengan gliserol1& 2a3es 0 es er dari ,A dg monohidric alcohol chain

II& +omple3 Lipids! mengand"ng' ,A! alkohol! fosfa ! 4B

/& ,osfolipid' )liserofosfolipid' P+! PE! PS! PISfingofosfolipid' Sfingomielin! +eramide

1& )likolipid ' +ere#roside' mengand"ng sa " resid"monosakarida&

)angliosida' mengand"ng oligosakarida5& 5&O her comple3 lipids'S"lfolipid!aminolipid! Lipopro ein

III& Prec"rsor . Deri-ed Lipids' S eroids! Lipid6sol"#le 7i !

Eicosanoids! KB&


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1. Simple lipids: Es ers !" "a # a$ids %i & 'ari!(s al$!&!ls.a. Fa s: Es ers !" "a # a$ids %i & )l#$er!l. Oils are "a s in &e li*(id s a e.

b. +a,es: Es ers !" "a # a$ids %i & &i)&er m!le$(lar %ei)& m!n!dri$al$!&!ls. -. !mple, lipids: Es ers !" "a # a$ids $!n ainin) )r!(ps inaddi i!n ! an al$!&!l and a "a # a$id . a. /&!sp&!lipids: Lipids $!n ainin)0 in addi i!n ! "a # a$ids and an al$!&!l0 a

p&!sp&!ri$ a$id resid(e. They frequently have nitrogen containing bases andother substituents, eg, in )l#$er!p&!sp&!lipids0 the alcohol is glycerol and insp&in)!p&!sp&!lipids &e al$!&!l is sp&in)!sine. b. Gl#$!lipids )l#$!sp&in)!lipids2: Lipids $!n ainin) a "a # a$id0sp&in)!sine0 and $ar3!dra e. c. O &er $!mple, lipids: Lipids s($& as s(l"!lipids and amin!lipids.Lip!pr! eins ma# als! 3e pla$ed in this category.

4. /re$(rs!r and deri'ed lipids : T&ese in$l(de "a # a$ids0 )l#$er!l0s er!ids0 ! &er al$!&!ls0 "a # aldehydes, ketone bodies (Chapter 22), hydrocarbons,ipid-soluble vitamins, and hormones.


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T&e LI/ID MA/S LI/ID Me a3!li es And /a &%a#s S ra e)#2


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S r"c "ral rela ionships of he ma(or classes of lipids&


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Klasi"i5asi #an) lain :

MA6OR lass LI/ID

1. FA

-. TAG4. F!s"!lipid:7 Gliser!"!s"!lipid : / 0 /E0 /I0 /S

7 S"in)!lipid:s"in)!mielin0 $ere3r!side0 )an)li!sida8. K!les er!l:


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Asam Lemak $ ,a y Acid%

• Deri-a asam kar#oksila dari ran ai pan(ang hidrokar#on

• Biasa dalam #en "k es er! e3' TA)

• 8m"mnya +/1 0 +19 $genap%• Sa "ra ed ,A 0 anpa ika an rangkap'e3' Palmi ic acid 8nsa "ra ed 0 dengan ika an rangkap $ cis a a" trans %' 6 Mono "nsa "ra ed ! e3' Oleic acid

6 Poly "nsa "ra ed! e3' Linoleic! linolenic arachidonic

TATA4AMA

• Sa "ra ed ,A ' #er6akhiran anoic! e3: ;e3adecacoic acid

• 8nsa "ra ed ' #erakhiran enoic! e3' Eicosa e raenoic acid

4"m#eringM"lai dari a om + kar#oksil se#agai nomor /! selan(" nya1! 5! < e c a a" =! >! ?! @! e c! e api a om + erminal

dise#" se#agai a om + $omega%


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• Shor chain ,A 1 6 < a om +• Medi"m chain ,A 9 0 / a om +• Long chain ,A /1 0 1< a om +• Palmi ic acid /9'• Oleic acid /C'/: • Arachidonic acid 1 '


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Essen ial ,A $E,A%P8,A 6 Linoleic acid' waln" ! whea germ oil! canola oil!

fish li-er oil! h"man milk! oganmea s! seafood H fa y fish&

Linolenic acid' plan oils' corn! pean" ! soy#ean!co on seed oils&

Arachidonic acid ' dihasilkan dari Linoleic acid&

F(n)si EFA• Pem#en "kan mem#ran sel• Perkem#angan o ak dan sis em saraf • Sin esis Eicosanoids' Pg! T3! L ! dengan efek a&l'

6 reg"lasi ekanan . -isosi as darah6 -asokons riksi6 respon imm"n

6 reaksi radang


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Common Saturated Fatty Acids


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Unsaturated Fatty Acids


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• Olive oil – from Oleo europa (olive tree)• Corn oil – from Zea mays• Peanut oil – from Arachis hypogaea• Cottonseed oil – from Gossypium• Sesame oil – from Sesamum indicum• Linseed oil – from Linum usitatissimum• Sun ower seed oil – from Helianthus

annuus• Ra eseed oil – from Brassica rapa• Coconut oil – from Cocos nucifera

!"am les of oils


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9 4 .

.9 4 .9 4 .9 4 .9 4

.OO9

/9 TANI A ID

A plan deri-ed fa y acid wi h /9 + and #ranches a + 5!+ ! +// and +/ & $me a# in *E %

Presen in dairy prod"c s and r"minan fa s&

A pero3isome responsi#le for he me a#olism of phy anicacid is defec i-e in some indi-id"als&

$phy anol6+oA dio3ygenase% 0 =6o3ida ionThis leads o a disease called *efs"mJs disease*efs"mJs disease is charac eri ed #y peripheralpolyne"ropa hy! cere#ellar a a3ia and re ini is pigmen osa


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Biochemical #asis

•Man"sia idak memiliki en im yang dapa memas"kkanika an rangkap pada posisi se elah a om + 6+/ !selama sin esis asam lemak&

• Struktur dab fungsi membran sel

• Transport kolesterol

• Pembentukan liporotein• Mencegah Fatty Liver

Fun#si S esi$% !FA


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Cis - Trans Fatty Acids


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• also known as sphingolipidoses• gene ically ac "ired• d"e o he deficiency or a#sence of a ca a#olic

en yme• e3amples'

• Tay Sachs disease• )a"cherJs disease• 4iemann6Pick disease•

,a#ryJs disease• http://www.ninds.nih.gov/disorders/lipid_storage_

diseases/lipid_storage_diseases.htm

Li id stora#e diseases

http://www.ninds.nih.gov/disorders/lipid_storage_diseases/lipid_storage_diseases.htmhttp://www.ninds.nih.gov/disorders/lipid_storage_diseases/lipid_storage_diseases.htmhttp://www.ninds.nih.gov/disorders/lipid_storage_diseases/lipid_storage_diseases.htmhttp://www.ninds.nih.gov/disorders/lipid_storage_diseases/lipid_storage_diseases.htm


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,a y Acid Me a#olism

Degrada ion and Syn hesis


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Fa # a$ids &a'e "!(r ma;!r psi!l!)i$al r!les

/& ,A are f"el molec"les! primary so"rce of energy $TA)%

1& B"ilding #locks of phospholipids and glycolipid

5& Many pro eins are modified #y he covalent attachmentof fatty acids, which targets them to membranelocations $)lycosyl phospha idylinosi ol $)PI% anchoror mem#rane anchor pro ein %&


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,a y Acid Degrada ion and Syn hesis MirrorEach O her in Their +hemical *eac ions


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TAG Are 9i)&l# !n$en ra ed Ener)# S !res

• TA) are highly concen ra ed s ores of me a#olic energy& 5C k $ kcal g6l%! -s / k $< kcal g6I% for K; and pro eins

• &asis of di'erence FA are muc more reducedandnon olar * stored in an ydrous form+( ,+-. / vs olar #lyco#en )

• B2 kg' reser-e energy' / & : 1


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Die ary Lipids Are Diges ed #y Pancrea ic Lipases

• Steatorrhea, bile salts ( ! due to liver disease• TA) incorpora ed in o micelles! composed of #ile

sal s


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Die ary Lipids Are Transpor ed in +hylomicrons

+M ' 1 nm! TA)! +! +E! PL! fa 6sol"#le -i amin dan

Apo6B


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8 ili a ion of ,A as ,"el *e "ires 5 S agesProcessing

1. Lipids m"s #e mo#ili ed ' TA) are degraded o ,A .glycerol! released . ranspor ed o he energy6 re "iring

iss"es&

1& A hese iss"es! ,A m"s #e ac i-a ed and ranspor edin o mi ochondria for degrada ion $o3ida ion%

5& ,A are #roken down in a s ep6#y6s ep fashion in o ace ylcoA! which is hen processed in he ci ric acid cycle&


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obili!ation of triacylglycerols

/& TA) are hydroly ed #y ;S Lipases


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)lycerol formed #y lipolysis is a#sor#ed#y he li-er


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"# FA are linked to CoA$S% before they are o&idi'ed

E& Kennedy . A Lehninger $/ < %' o3idi ed in mi ochondria

/a(l Ber)


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A$e #l !A0 NAD90 and FAD9- Are Genera edin Ea$& R!(nd !" Fa # A$id O,ida i!n


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+omple e O3ida ion of Palmi a e Nields / 9Molec"les of ATP

( & )* ! + (, & )#- ! + ( , & "#- ! . " / )*0

Ne AT/ #ield:


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• An 1somerase and a 2eductase Are 2e3uired for the 4&idation of 5nsaturated Fatty Acids

t%o additional en&!ymes an isomerase and a reductase are needed to degrade a %iderange of unsaturated fatty acids.

o'idation of polyunsaturated fatty acids


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Odd7 &ain Fa # A$ids ield /r!pi!n#l !A in&e Final T&i!l#sis S ep


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Ke one Bodies Are ,ormed from Ace yl+oA2hen ,a Breakdown Predomina es


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6etone 7odies Are a Ma8or Fuel in Some Tissues


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Fa # a$id s#n &ase m(l ien


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• ,A syn hesis s ar s wi h he car#o3yla ion of ace yl +oA

o malonyl CoA. his irreversible reaction is thecommitted step in fatty acid synthesis.


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• Mammals lack the enzymes to introduce double bonds at carbonatoms beyond C-9 in the fatty acid chain.• Hence mammals cannot synthesize lin!lea e 1=:- $is7>0 1-2 and

lin!lena e 1=:4 $is7>0 1 - 01?2 .• Linoleate and linolenate are the two essential fatty acids.• The term essential means that &e# m(s 3e s(pplied in &e die

3e$a(se &e# are re*(ired 3# an !r)anism and $ann! 3es#n &esi


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Composition of the Ma8or Lipoprotein Comple&es


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;yperlipopro einemia


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0 li i i


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0y oli o roteinemia


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Ara$&id!na e is &e ma;!r pre$(rs!r !" ei$!san!ids .$rostaglandin synthase cataly!es the first step in a path%ay leading to $ , $C, T

*ipo'ygenase cataly!es the init ial step in a path%ay leading to leukotrienes (*T)

Ap!pr! ein lassi"i$a i!ns


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• /r!s a)landins s im(la e in"lamma i!n0 re)(la e 3l!!d "l!% !par i$(lar !r)ans0 $!n r!l i!n ransp!r a$r!ss mem3ranes0m!d(la e s#nap i$ ransmissi!n0 and ind($e sleep.


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6O3ida ion

edium chain (C + -+2), et.endoplama dan gin al ( escue $ath%ay)


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S hi li id


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Sphingolipids

The core of sphingolipids is he long6chain amino alcohol!

sphingosine& Amino acyla ion! wi h a long chain fa y acid!a car#on 1 of sphingosine yields a ceramide&

#phingosine Ceramide

• #phingomyelin, synthesi!ed by the transfer of phosphorylcholine

from phosphatidylcholine to a ceramide in a reaction cataly!ed bysphingomyelin synthase.

• lycosphingolipids/ cerebrosides, sulfatides, globosides andgangliosides.

Dis!rders Ass!$ia ed %i & A3n!rmal Sp&in)!lipid Me a3!lism


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represents the linkage to protein in the secreted forms, sphingolipid (ceramide) in thecell-surface bound form, open square 0 lc1 c, open diamond 0 galactose, filledsquare 0 fucose, filled diamond 0 al1 c. The linkage in the glycolipid form mayinclude a glucose in a 3-+,4 or 3-+,5 to the initial galactose residue.


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De"e$ i'e Gl#$!pr! ein De)rada i!n LSD2


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$ $ p )


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The cell"lar s"pply of choles erol is main ained

a a s eady le-el #y hree dis inc mechanisms' /& *eg"la ion of ;M)* ac i-i y and le-els

1& *eg"la ion of e3cess in racell"lar free choles erolhro"gh he ac i-i y of acyl6+oA'choles erol

acyl ransferase! A+AT

5& *eg"la ion of plasma choles erol le-els -ia LDL

recep or6media ed "p ake and ;DL6media ed re-erseranspor &


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Bile Acids as Me a#olic *eg"la ors


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Bile acids were originally iden ified as #eing in-ol-ed info"r primary physiologically significan f"nc ions'/& heir syn hesis and s"#se "en e3cre ion in he feces

represen he only significan mechanism for heelimina ion of e3cess choles erol&

1& #ile acids and phospholipids sol"#ili e choles erol in he#ile! here#y pre-en ing he precipi a ion of choles erol in

he gall#ladder&

5& hey facili a e he diges ion of die ary riacylglycerols #yac ing as em"lsifying agen s ha render fa s accessi#le opancrea ic lipases&

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2.METABOLISME LIPID (prf.frans).pptx