Cellular Metabolism [Autosaved]

8/20/2019 Cellular Metabolism [Autosaved]

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CELLULARMETABOLISM

DR ERMIN RACHMAWATI, M.BIOMED.


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Chemical andphysical reaction

LI- Catabolism- Anabolism


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c a t a b

o l i s m

Aminocar bo!dr at"

l i # id

N$cl"ic acid

#r ot"in

%l$cos",& r

As"t!

D N

ENERGY

A T '


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A n a b

o l i s m

- need energy


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S"tia# or(an m"mili)i)ara)t"r m"taboli) !an(


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OTA

* + %l$)osa adala baan ba)ar $tama

ECE'TION )"la#aranb"r)"#an-an(an

D"#o cadan(an baan ba)ar r"nda

/0 #"man&aatan (l$)osa t$b$

En"r(i di ota) di($na)an $nt$)

+. M")anism" trans#ort a)ti&

m"m#"rtaan)an #ot"nsialm"mbran Na1*

2. Sint"sis n"$rotransmitt"r

3. Sint"sis #rot"in !an( #"ntin( $nt$)trand$)si sin!al


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ran(

)a + Baan ba)ar $tama otot ran()a

+. (l$)osa

2. 44A

3. Badan )"ton

'ada )ondisi istiraat, baan ba)ar di($na)an $nt$) mn(asil)an "n"r

44A

%l$)osa m"n-adi dominan di($na)a

baanba)ar otot ran()a #ada 2 )on

Latian mod"rat"1int"ns"

B"b"ra#a -am s"t"la ma)an #ada sins$lin m"nin()at


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ran()a

2 D"#o (li)o("n b"sar 6+2//)*al17//

En:im (l$)osa #os#atas" san(at

%l$)osa di ba;a )" dalam otot ran(

m"lal$i %LUT<

*ontra)si otot ran()a 5

La-$ (li)olisis tin((i, la)tat tin((i dib

ati 6si)l$s =ori9 T"rb"nt$)n!a alanin


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8ant$

n( Otot -ant$n( b"rsi&at a"robi) )ar"nadit"m$)an mito)ondria #adat Tida) m"mili)i cadan(an (li)o("n

Baan ba)ar $tama 44A

Badan )"ton as"toas"tat la)tat s"bbaan ba)ar cadan(an


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%IN8

AL Baan ba)ar $tama (in-al adala (l '"ma)aian o)si("n $nt$) #"n!"dia

"n"r(in!a t"r(ant$n( o)si("n

S"lama )"la#aran, (in-al m"r$#a)a

(l$)on"o("n"sis $tama b"rsama a


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LI>E

R Baan ba)ar $tama $nt$) ati adal

(l$)osa

S"("ra s"t"la )ons$msi ma)anan,

m"n(ambil 213 (l$)osa dara dan d

-adi (l$)osa '

SUMBER baan ba)ar ota), otot dan

-arin(an #"ri&"r lain

SUMBER baan ba)ar -arin(an #"ri&

cara

'"m"caan (li)o("n ati

%l$)on"o("n"sis


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ib (l$)osa ' di ati

li)olisis1si)l$s as.sitrat1&os&orilasi o)si

. *on?"rsi m"n-adi (li)o("n

n s"t"la +,2 di$ba -adi as) asam l"ma), )ol"st"rol da


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LI>E

R R"($lator m"tabolism" asam l"ma)

R"($lator m"tabolism" asam amino

R"($lator ($la dara


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“

”

Ma-or "n"r(! mol"c$l" o&o$r Bod! isAT' 6Ad"nosin"

Tri'os#at"9


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at# D"@nition 5 s"b$a n$)l"otida !an(

dari ad"nosin, dan 3 )"lom#o) &os&a

M"n(and$n( "n"r(i )imia !an( t"rs

#ada i)atan &ostan!a

En"r(i dil"#a)an )"tia AT' m"n(ala#ros"s HIDROLISIS

4$n(si AT' 5

'"r("ra)an s"l

Trans#ort m"lal$i m"mbran s"l

Sint"sis mol")$l or(ani)

Transd$)si sin!al


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• 6&rom t" %r"") glycos, s$(ar,

lysis, br"a)do;n9 is a #at;a! #artiall! cataboli:"scarbo!drat"s,#rimaril! (l$cos

• It consists o& +/ "n:!matic r"ac

• con?"rt a sicarbon mol"c$l" o(l$cos" into t;o tr""carbonmol"c$l"s o& pyruvate,t" ion&orm o& #!r$?ic acid.

• r"actions #rod$c" a n"t (ain o&

Glycolysis


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"nt"r t" *r"bs c!cl"

and b" bro)"n do;n intocarbon dioid",

R!"#E F"#E

O2

con?"rt"d to lactat

6t" ioni:"d &orm o&b! a sin(l" "n:!m"mr"action.


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"(l!col!sis En"r(i asil R"a)si !an( di)atalisis ol" &os&o(lis"rat )inas" ilan(

s"ba(ai #anas

'ros"s ilan(n!a "n"r(i AT' dan di(anti)an s"ba(ai #anas di)atalisisol" "n:im bi&os&o(lis"rat m$tas"

+,3 bi&os&o(lis"rat 2,3 bi&os&o(lis"rat" 3bi&os&o(lis"rat"

8al$r alt"rnati& ini b"r&$n(si 5 m"n!dia)an 2,3 bi&os&o(lis"rat !an(m"n(i)at "mo(lobin s"in((a m"n$r$n)an a@nitas t"rada# o)si("ndan m"mb$at o)si("n l"bi m$da t"rs"dia dan dil"#as)an -arin(an


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“

”*REB CCLE

6SI* L US ASAM S

I TRA T1SI* L U T

TRIICARBO* SILI

C ACID 6 TCA 9 9

T"r-adi di matri)s mito)ondria


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T"r-adi di matri)s mito)ondria

Baan ba)$ 5 44A, asam amino, )arboidrat6#ir$?at9, dimana s"m$a baan ini a)an di$ba )"dalam b"nt$) As"til *oA

R"a)si o)sidasi r"d$)si 6o)sidasi (r$# as"til darias"tilCoA9

Si)l$s asam sitrat m"n("l$ar)an "l")tron dari as"til)oA 6#ada H9 dan ditrans&"r )" NADH dan 4ADH2,dimana "l")tron NADH dan 4ADH2 a)an didonor)an#ada #ros"s &os&orilasi o)sidati&

Si)l$s )r"bs m"n(asil)an

NADH

2 4ADH

2 %T' 6%T' a)an m"n(alami idrolisis m"mb"nt$)

AT'9


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O)saloas"tat bisa di($na)an $nt$) smol")l or(ani) s#t #rot"in

8i)a o)saloas"tat di($na)an $nt$) siasam amino a?aibilitas baan int"rmsi)l$s )r"bs b"r)$ran(.

M")anism" $nt$) m"m#"rtaan)an)"b"radaan o)saloas"tat 5

>ERSI 'IRU>AT DAN ASAM AMINO TERTENTU


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4os&orilasio)sidati&


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'ros"s dimana AT' dib"nt$) s"ba(ai asil trans&"r "ldari NADH14ADH2 )" O2 ol" s"ran()aian )ari"r "l")#ada )om#l")s #rot"in

Lo)asi 5 m"mbran dalam mito)ondria

Donasi "l")tron dari NADH dan 4ADH2 m"n!"bab)an

t"r-adin!a #om#a #roton b"r$#a ion H dari matri)smito)ondria )" r$an( int"rm"mbran mito)ondria.

'om#a #roton ini m"n!"bab)an t"r-adin!a #"rb"daa(radi"n "l")tro)imia !an( di($na)an ol" AT' sintas$nt$) m"m#rod$)si AT'


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$ %omple%s protein ter&enamdi mem&ran dalam

mito%ondria


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*om#l")s #rot"in

*om#l")s #rot"in I 5 NADH =o)sidor"d$)tas"

*om#l")s #rot"in 2 5 S$ccinat= r"d$)tas"

*om#l")s #rot"in 3 5 Sito)orom bc+

*om#l")s #rot"in < 5 sito)rom c o)sidas"

' %omple%s protein (),',$* adalahpompa proton


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(l$)on"o("n"sis


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(l$)on"o("n"sis S"m$a -al$r !an( b"rtan(($n(-a;ab m"r$ba #r")$rsor non)

m"n-adi (l$)osa

B$)an r"a)si )"bali)an dari (li)olisis

S$bstrat ata$ baan ba)$ 5La)tat

%lis"rol

'ir$?at

Asam amino 6(l$tamin, alanin9

8arin(an $tama t"m#at (li)o("nolisis adala 5 li?"r dan (in-al

%l$)on"o("n"sis an!a a)an t"r-adi -i)a t$b$ m"mb$t$)annam$n (l$)osa dara san(t r"nda dan d"#o (li)o("n tida) lm"nc$)$#i

In (l$con"o("n"sis, ada tambaan taa#an r"a)si s"ba(ai -a

alt"rnati& dari r"a)si ir"?"rsib"l #ada (li)olisis


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'ros"s )on?


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REA*SI DARI 'IRU>AT *E 4OS4OENOL

'ros"s )on?&r$)tosa +,B'&r$)tosa ' at"r-adi di ati, (iotot ran()a 6tida)otot -ant$n(Dan otot #olos

'ros"s )on?"(l$)osa ' (l$)osaan!a t"r-adi di a(in-al, tida) di otran()a dan s"l adi#os

S i ) l $ s F

o r i


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%LI*O%ENESIS

'ROSES SINTESIS %LI*O%EN

%li)o("n m"r$#a)an 5

B"nt$) sim#anan (l$)osa

'olim"r r"sid$ (l$)osa dan b"rcaban(

2 lo)asi #"n!im#anan $tama adala li?"r dan otot ran()a

*ons"ntrasi (li)o("n ati 6+/09 G(li)o("n otot 6209 %li)o("n t"rda#at dalam b"nt$) (ran$l

Sint"sis (li)o("n m"mb$t$)an

%l$)osa

UD' (l$)osa


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4$n(si (li)o("n Dalam ati 5 sint"sis dan d"(radasi (li)o("n b"rt$-$an $nt$)

m"m#"rtaan)an )adar ($la dara dalam )isaran normals"in((a "n"r(i $nt$) -arin(an #"ri&"r t"ta# di#"rtaan)an

Dalam otot 5 sint"sis dan d"(radasi (li)o("n b"rt$-$an $nt$)m"m"n$i )"b$t$an otot a)an (l$)osa

%li)o("n otot, Han!a b"r&$n(si $nt$) s"l otot

Hal ini di)ar"na)an s"l otot anm"mili)i "n:im (l$)osa #os#m"n()atalisis r"a)si )on?"rsi ((l$)osa 6(li)o("nolisis9 ata$6(l$)on"o("n"sis9

*ar"nan!a (l$)osa otot tida) bil$ar

i li) i


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En:im (li)o("n"sis

%li)o("n sintas" )atalisa sint"sis i)atan +,<α (li)osidi)

Trans&"ras" dan α +, (li)osidas"

2 "n:im t"ra)ir m"mb"nt$) i)atan +, !an(

m"mb$at (li)o("n m"n-adi #olim"r b"rcaban( '"rcaban(an #"ntin )ar"na

M"nin()at)an sol$bilitas dari (li)o("n

M"nci#ta)an ban!a) r"sid$ t"rminals"in((a )"r-a "n:im &os&orilas" dan sintas"


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METABOLISME LEMA*

TRI%LISERIDA


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TRI%LISERIDA

BENTU* dominan l"ma) $nt$)m"n(asil)an "n"r(i

Monom"r tri(lis"rida adalaasam l"ma)

*ol"st"rol tida) m"n(and$n(asam l"ma) nam$n inti st"roln!am"r$#a)an ba(ian dari mol")$l

asam l"ma)

L"ma) dalam ma)anan , 3b"nt$)

Tri(lis"rida

*ol"st"rol

4os&oli#id

' ' ti A L )


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'"ran '"ntin( Asam L"ma)

Ran()a &os&oli#id dan (li)oli#id Modi@)asi #rot"in

Mol")$l baan ba)ar

Hormon dan #"rantara intras"l$l"r

Tri(lis"rida


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Tri(lis"rida

Ti(a asam l"ma) !an( b"ri)atan d"n(an (lis"rol 8"nis asam l"ma) #"n!$s$n tri(lis"rida 5

Asam st"arat

Asam ol"at

Asam #almitat


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3 taa# li#id s"ba(ai s$mb"r


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3 taa# li#id s"ba(ai s$mb"r"n"r(i

Mobilisasi li#id A)ti?asi l"ma) dan dian()$t )" mito)ondria d"(radasi 44A

Di mito)ondria 44A di#"ca s"cara b"rtaa# m"n-adi as"til )o!an( a)an mas$) si)l$s )r"bs

8ARIN%AN #"ri&"r


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8ARIN%AN #"ri&"r

A)ti?asi 44A ac!lCoA dila)$)an di m"mbran l$ar mito)ondria

M")anism" #"n(an()$tan ac!lCoA d"n(an cara )on-$(asi aclCOa d"n(acarnitin aclcarnitin dan di)atalisis ol" "n:im ac!l carnitin trans&"ras"

Acil carnitin m"n"mb$s m"mbran dalam mito)ondria m"lal$i #ros"stranslo)asi

%r$# ac!l b"ri)atan d"nan Co A di matri)s mito)ondria

Carnitin di trans&"r )"l$ar )" sitosol

Ac!l CoA )"m$didan did"(radasi m"lal$i < taa#

O)sidasi ol" 4AD

Hidrasi

O)sidasi ol" NAD

Tiolisis ol" COA

BADAN *ETON


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BADAN *ETON

As"til )oA asil o)sidasi b"ta mas$) si)l$s )r"bs HANA 8I*A ada)"s"imban(an antara d"(radasi *H dan l"ma)

Alasan 5

Mas$)n!a as"til )oA )" dalam si)l$s asam sitrat t"r(ant$n()"t"rs"diaan o)saloas"t

'ada )ondisi #$asa lama ata$ )"la#aran

*ons"ntrasi o)saloas"tat m"n$r$n As"til )oA a)an m"mb"nt$)

Asam as"toas"tat

D3 idro)sib$tirat


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HORMONHORMON

'AN*REAS

T" #ancr"as is com#os"d o& t;o ma-or t!#"s o& tiss$"s,6+9 t" acini, ;ic s"cr"t" di("sti?" -$ic"s into t" d$od"n$m6 9 i l f h i i li d l


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629 t" islets of Langerhans, ;ic s"cr"t" ins$lin and (l$ca(ont" blood.

T" $man #ancr"as as + to 2 million isl"ts o& Lan("rans, "a

/.3millim"t"r in diam"t"r and or(ani:"d aro$nd small ca#illari"s inc"llss"cr"t" t"ir ormon"s.

3ma-or t!#"s o& c"lls, alpha, beta, and delta c"lls, ;ic ar" dis

&rom on" anot"r b! t"ir mor#olo(ical and stainin( C.• T" b"ta c"lls, constit$tin( abo$t / #"r c"nt o& all t" c"lls

and s"cr"t" insulin and amylin• T" al#a c"lls, abo$t 27 #"r c"nt o& t" total, s"cr"t" gluca• t" d"lta c"lls, abo$t +/ #"rc"nt o& t" total, s"cr"t" somato• In addition, t" '' c"ll, is #r"s"nt in small n$mb"rs in t" isl"


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0ormon

Insulin

Ins$lin is a #rot"in consistin( o& 7+ amino acids contain"d ;itin t;o #"cains5 an A cain, ;it 2+ amino acids and a B cain, ;it 3/ amino ac i d b di l@d b id


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cains ar" conn"ct"d b! t;o dis$l@d" brid("s.an intracain dis$l@d" brid(" tat lin)s #ositions and ++ in t" A cainmol"c$lar ;"i(t o& $man ins$lin is 7/.

Mat$ration o& s"cr (ran$l" 5 loss o& clatrin Con?"rsion into ins$lin and C


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sort arm o& cromosom

%"n" "#r"ssion #rod$c

'r"#roins$lin is cl"a?"d b!microsomal "n:!m"

trans#ort"d to A## (ol(i 'ac)a(in( clatrin coat"d s"

(ran$l"s

Con?"rsion into ins$lin and C

esis Insulin

i i li


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resi insulin *ar"na str$)t$r isl"t #an)r"as !an( )a!a ?as)$lat$r, )ons"ntras

(l$)osa !an( tin((i b"r#"ran s"ba(ai s"nsor $nt$) mas$)n!a(l$)osa )" dalam s"l 6masi ada #"rd"batan m"n("nai #"ran%LUT29

%l$)osa di dalam s"l a)an m"n(alami s"ran()aian r"a)si(li)olisis asam sitrat m"mb"nt$) AT'


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a small #rot"in $man ins$lin as a mol"c$lar ;"i(t o& 7/.


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It is com#os"d o& t;o amino acid cains, conn"ctot"r b! dis$l@d" lin)a("s.W"n t" t;o amino aar" s#lit a#art, t" &$nctional acti?it! o& t" ins$li

mol"c$l" is lost.

Ins$lin is s!nt"si:"d in t" b"ta. CELL Tis initial #r"#roormon" as a mol"c$lar ;"i(++,7//, b$t it is t"n cl"a?"d in t" "ndo#lasmic

to &orm a proinsulin ;it a mol"c$lar ;"i(t o& ab

most o& tis is &$rt"r cl"a?"d in t" %ol(i a##arains$lin and #"#tid" &ra(m"nts b"&or" b"in( #ac)a

s"cr"tor ran$l"s


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T" ins$lin binds ;it t" al#a s$


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on t" o$tsid" o& t" c"ll,b$t b"cat" lin)a("s ;it t" b"ta s$b$nits

#ortions o& t" b"ta s$b$nits #rotrinto t" c"ll b"com" a$to#os#or

a$to#os#or!lation o& t" b"ta s$t" r"c"#tor acti?at"s a local tyroskinase, ;ic in t$rn ca$s"s#os#or!lation o& m$lti#l"

se #R"N1P2R#ER


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GL# ) is #r"s"nt in all $man tiss$"s. It a##"ars to m"diat" basal (l$cos"a ?"r! i( anit! &or (l$cos" and t"r"&or" is abl" to trans#ort (l$cos" at conc"ntrations as &o$nd in t" basal stat". 4or tis r"ason, it is an im#ortanbrain ?asc$lar s!st"m 6bloodbrain barri"r9 to "ns$r" ad"F$at" trans#ort o&

CNS

GL# ', ;ic is also &o$nd in all tiss$"s, is t" ma-or (l$cos" trans#ort"r os$r&ac". It also as a ?"r! i( anit! &or (l$cos" and is r"s#onsibl" &or trainto n"$ronal c"lls.

GL# / as a ?"r! lo; anit! &or (l$cos" and s""ms to act as a trans#ort"

(l$cos" l"?"ls ar" r"lati?"l! i(, s$c as #ost #randiall!. It is a ma-or trans"#atic, int"stinal, and r"nal t$b$lar c"lls, so tat diK$sion o& (l$cos" acrosincr"as"s as (l$cos" l"?"ls ris". T" lo; anit! o& %LUT 2 &or (l$cos" r"d$c(l$cos" d$rin( t" basal stat" or d$rin( &astin(. %LUT 2 is also "#r"ss"d oB c"lls in rod"nts, b$t it is not d"t"ct"d at si(ni@cant l"?"ls on $man B c"l

GL# $ is &o$nd in t;o ma-or ins$lin tar("t tiss$"s5 s)"l"tal m$scl" and ad

a##"ars to b" s"F$"st"r"d mainl! ;itin an intrac"ll$lar com#artm"nt o& t


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e end e3ects o insulin s

)

/

S"("ra

c"#at

8an()a #an-an('

- U#ta)" (l$)osa dl s"l mn()at- '"rm"abiltas m"mbran td ion

- '"r$baan a)ti?itas "n:im i

- '"nin()atan #rot"in 6transdan translasi

-M"tabolism"


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W"n t" F$antit! o& (l$cos" "nt"rin( t" li?"r


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W"n t" F$antit! o& (l$cos" "nt"rin( t" li?"rc"lls is mor" tan can b" stor"d as (l!co("n or canb" $s"d &or local "#atoc!t" m"tabolism, insulin

promotes the conersion of all this e!cess glucoseinto fatty acids.

Ins$lin also inhibits gluconeogenesis. It do"s tis


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Ins$lin also inhibits gluconeogenesis. It do"s tismainl! b! d"cr"asin( t" F$antiti"s and acti?iti"s o& t" li?"r "n:!m"s r"F$ir"d &or (l$con"o("n"sis.Ho;"?"r, #art o& t" "K"ct is ca$s"d b! an actiono& ins$lin tat d"cr"as"s t" r"l"as" o& amino acids

&rom m$scl" and ot"r "tra"#atic tiss$"s and int$rn t" a?ailabilit! o& t"s" n"c"ssar! #r"c$rsorsr"F$ir"d &or (l$con"o("n"sis.


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E&") *H

M"tabolis


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0ormonGlu%agon


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a lar(" #ol!#"#tid", mol"c$lar ;"i(t o& 3


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M")anism" (li)o("n"sis dan


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#"nin()atan ($la dara

acti?at"s adenylyl cyclase in t" "#aticc"ll m"mbran"o& cyclic adenosine monophosphate acti?at"s protein regulator protein acti?at"s protein kinase acti?at"s phosphorylase b kinase, Wic con?"rts phosphorylas phosphorylase a #romot"s t" d"(radation o& (l!co("(l$cos"+#os#at" t"n is d"#os#or!lat"d and t

r"l"as"d &rom t" li?"r c"lls


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%l$ca(on in ?"r! i( conc"ntrations also 6+9"nanc"s t" str"n(t o& t" "art 629 incr"as"sbloodo; in som" tiss$"s, "s#"ciall! t" )idn"!s 639"nanc"s bil" s"cr"tion and 6


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(l$)a(on '"nin()atan asam amino '"nin()atan )dar ($la dara

stomatostatin

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