DEP
DEPARTMENT OF BIARTMENT OF BIOCHEMIOCHEMISTRYYSTRYY
MEDICAL FACULTI OF
MEDICAL FACULTI OF
HASANUDDIN UNIVERSITY
HASANUDDIN UNIVERSITY
1,2
1,2 Marhaen Marhaen HardjoHardjo
1
1Head of Biochemistry Department, Medical Faculty of Hasanuddin Head of Biochemistry Department, Medical Faculty of Hasanuddin UniversityUniversity
2
2Director of Stem Cell Center Hasanuddin Director of Stem Cell Center Hasanuddin University HospitalUniversity Hospital INTERRELASI
INTERRELASI METABOLISME DANMETABOLISME DAN
PENGATURANNYA
KERANGKA SLIDE
KERANGKA SLIDE
•
• PENGERTIAN INTERELASI METABOLISMEPENGERTIAN INTERELASI METABOLISME
•
• PROSES YANG TERJADI DALAM INTERELASI METABOLISMEPROSES YANG TERJADI DALAM INTERELASI METABOLISME
•
• HASIL INTERELASI METABOLISMEHASIL INTERELASI METABOLISME
•
PENDAHULUAN
PENDAHULUAN
kegiatan organisme memerlukan
kegiatan organisme memerlukan
perubahan energi dan reaksi kimia
perubahan energi dan reaksi kimia..
Metabolisme
Metabolisme
ANABOLISME
ANABOLISME
Glukosa Glikoge
As.le!ak " Glise#ol T#iglise#i$a
As. A!io P#o%ei
KATABOLISME
Glikoge Glukosa
T#iglise#i$a glise#ol " As.le!ak
Reaksi Anabolisme dan Katabolisme
berlangsung secara cepat Ter!adi karena adan"a katalisator "aitu en#im $molekul protein%& ber'ungsi secara cepat karena adan"a ( ko en#im "aitu beberapa )itamin B
*omple+ dan ko'aktor "aitu beberapa mineral serta adan"a media air
The main
source o'
energ"
carboh"d rates ,rotein -atsInterelasi
Metabolisme
adalah
proses metabolisme karbohidrat&
lemak& protein "ang pada mulan"a
berproses masing.masing tetapi
pada
akhirn"a
akan
saling
berinteraksi pada suatu siklus "ang
dinamakan siklus kreb
,engertian interelasi metabolisme
• ,ROSES /AN 0ASIL /ARI INTERELASI METABOLISME TER1TAMA ENER2I ,OTENSIAL A/ALA0 ,ROSES
TER3A/IN4A METABOLISME ENER2I 4AN2 BERS1MBER /ARI MOLEK1L KARBO0I/RAT& LEMAK& /AN ,ROTEIN&
TER3A/I /I/ALAM MITOKON/RIA /AN AKAN MEN20ASILKAN SE31MLA0 ENER2I
O1T,1T50ASIL AK0IR
INTERELASI METABOLISME
,enguraian 6 gram glukosa $karbohidrat% men!adi *O7& 07O
Energi 8 Kkal
,enguraian 6 gram aslemak $lemak% men!adi *O7& 07O
Energi 9 Kkal
,enguraian 6 gram asamino $protein% men!adi *O7& 07O dan N0: Energi 8 Kkal
Karbohidrat Lemak ,rotein
6 -ase khusus masing.masing $oksidati'% 7 -ase bersama $siklus krebs%
-ungsi Energi dari penguraian AT,
UNTUK SEL
M;bntuk molekul baru
Mngganti struktur sel "g rusak
Mengeluarkan dan memasukkan #at.#at dari dan kedalam sel
Membentuk molekul cadangan energi
1NT1K ,ER2ERAKAN OTOT
Aakti' maupun istirahat
/iperintah otak maupun tidak ada perintah dari otak
1NT1K KE,ERL1AN SEL
,roses pencernaan& pen"erapan& dan mengangkut #at gi#i
SE*ARA KESEL1R10AN ENER2I $KALORI% 42 /I0ASILKAN /ARI ,EN21RAIAN AT, AKAN /I21NAKAN 1NT1K (
&. AKTI'ITAS SAAT TUBUH ISTIRAHAT BASAL (BASAL ENERGY E)PENDITURE *BEE+
,. AKTI'ITAS 'ISIK (A'+
. PENGARUH TERMIS DARI MAKANAN (THERMI E''ET O' 'OOD* TE'+
Seluruh energi "ang digunakan tubuh adalah ,en!umlahan dari BEE < A- < TE- = Energi $kalori % total
&
Akti'itas saat tubuh istirahat basal $Basal Energ" E+penditure 5BEE%
• ,roses metabolisme dlm
sel
• /en"ut !antung
• 2rakan peristaltik usus • Tonus otot& etc
/
Rumus /u Bois
• BEE Pria = 66 + (13! " BB k#$ + (%"TB &m$ ' (6 " U) T*$
• BEE ,t = 6%% +(-6 " BB k#$ + (1 " TB &m$ '(.! " U) T*$
*ara cepat5 cara lain (
• BEE ,ria = :> kkal + kg BB • BEE ?anita = 7@ kkal + kg BB
Faktor0aktor a# mem2e#aru*i ilai BEE
• 1mur • 3K
• Suhu tubuh dan lingkungan
, Akti'itas 'isik $A-%
• Ak%i0i%as saga% #iga $a #iga 1 2 3 42 5 BEE
• Ak%i0i%as se$ag 42-645 BEE
• Ak%i0i%as 7e#a% 645 BEE
RUMUS Meg8i%ug Nilai A' Jeis A' 9 Ju!la8 BEE
Thermic E''ect o' -ood $TE-%
Nilai TE' 7iasa $ise7u% :uga $ega S;e<i0ik Dia!ik A<%io1 SDA. Nilai TE' u%uk ;#o%ei a$ala8 %e#%iggi 2 5= lalu ka#7o8i$#a%= ke!u$ia le!ak. SDA
7eke#:a !ulai $a#i TE' %e#%iggi ke!u$ia ?ag %e#e$a8. Ka#ea !eu !akaa !e#u;aka ga7uga ;#o%ei= ka#7o8i$#a% $a le!ak= !aka ilai TE'
• ONTOH PERHITUNGAN ENERGI UNTUK PA RAHMAT YANG BERUMUR 2 TAHUN= BB12 KG DAN TB1&2 M= AKTI'ITAS SEHARI-HARINYA DIKATEGORIKAN SEDANG (425+. BEE (ARA DU BOIS+ BEE PRIA 1 @ (&.6 ) BB KG + @ ( 4 ) TB M + 3 ( =C ) U.THN + 1 &42 KKAL
• AKTI'ITAS 'ISIK SEDANG ( 42 5 + 1 42 5 ) &42 KKAL 1 6,4 KKAL
• TE' 1 &2 5 ) (BEE @ A' + 1 &2 5 ) (&42@6,4+ 1 ,&6.4
• MAKA TOTAL KESELURUHAN PENGGUNAAN ENERGI ( TOTAL ENERGI E)PENDITURE 1 TEE + ADALAH PENJUMLAHAN DARI / 1 BEE @ A' @ TE' TEE 1 &42 @ 6,4 @ ,&6.4 1 ,,.4
Metabolic
Liver- #1 metabolic player
•Processes most incoming nutrients
•Maintains constant concentrations of nutrients
in blood (e.g., via gluconeogenesis), smoothing out fluctuations due to the Starve-Feed Cycle
•Synthesizes and secretes plasma proteins
•Processes toxins and wastes (e.g., through urea
cycle)
•Responds quickly to dietary conditions because of
Liver- #1 metabolic player
•Primarily depends
on b-oxidation of fatty acids for its own energy needs.
Liver
•Amino acids go directly
to the liver through the portal vein after
absorption.
•Uses them to make
proteins, for
gluconeogenesis, for
biosynthesis of nitrogen-containing molecules, or for fuel.
Adipose Tissue- maintainer #2
•Stores triglycerides and releases FA’s
and glycerol as signaled by glucagon/ epinephrine
Albumin transport in blood
muscle heart liver
•Turnover is 50-60 g/day.
triglyceridescAMP-activatedfatty acids + glycerol
•Two distinct
types: white
adipose tissue and brown adipose
tissue.
•Brown fat has
high levels of thermogenin, which are metabolically activated by cold exposure. Huffington Post
Less than two weeks after finishing the 2010 Boston Marathon in 4:10, disaster struck for Paul J in the
Pitts!urgh Marathon He ran the first half in 2:04 and the second half in 2:40 "e#ere leg cra$%s set in at around $ile 20, and he ended u% on the ground screa$ing in %ain &he da' was cool, and he took in lots of electrol'tes
Case Study: Paul J. cramps up
Less than two weeks afterfinishing the 2010 Boston Marathon in 4:10, disaster struck for Paul J in the
Pitts!urgh Marathon He ran the first half in 2:04 and the second half in 2:40 "e#ere leg cra$%s set in at around $ile 20, and he ended u% on the ground screa$ing in %ain &he da' was cool, and he took in lots of electrol'tes
(hat %ro!a!l' went wrong for Paul)
a* Lactic acid+
!* His fat stores ran out
c* His !lood sugar dro%%ed
d* arnitine deficienc'+
-Phos%hagen s'ste$*
Match the %hoto to the energ' s'ste$+
a* 1. lactate/ 2. %hos%hagen/ . aero!ic !* 1. %hos%hagen/ 2. aero!ic/ . lactate c* 1. aero!ic/ 2. lactate/ . %hos%hagen d* 1. aero!ic/ 2. %hos%hagen/ . lactate
• ATP exhausted rapidly (1 or 2 sec); replenished by:
Anaerobic Conditions- bursts
of
heavy activity
•phosphocreatine lasts ~10 seconds
•next 1 to 2 minutes
glycogen -> G-6P -> pyruvate -> lactate
Anaerobic Conditions- bursts
•Cooperation
between muscle and liver (Cori cycle) to regenerate glucose from lactate.
•Heart also burns
lactate.
• WITH LOW INTENSITY WORK, LACTATE IS CLEARED FROM THE BLOODSTREAM AS FAST AS IT IS MADE.
• AS WORK INCREASES, THERE IS A POINT WHEN LACTATE IS
PRODUCED TOO FAST FOR THE BODY TO CLEAR IT.
work
ercise cannot !e sustained for $ore than a $inute or two after lactate threshold !ecause of P351 inhi!ition
1. glycogen -> G-6P -> pyruvate -> CO2 + H2O
2. fatty acids -> acetyl-CoA -> CO2 + H2O
•Limited by diffusion of FA’s from blood, carnitine
Aerobic Conditions- rest,
slow
runs, light activity
•Limited by entry of pyruvate into mitochondria
and/or O2 supply
•1- 2 hour supply, moderately fast
Cross Country Collapse
$il', the 62 ranked fe$ale highschool cross countr' runner in the state, is co$%eting in the (estern
Maine cha$%ionshi% "he goes into the woods 7ust !efore the $ile $ark !ut
doesn8t co$e out
"he had !een struggling the entire season, feeling weak and tired, and
had dro%%ed out of three races %rior to this $eet (hat t'%e of testing would 'ou do on $il')
Cross Country Collapse
$il', the 62 ranked fe$ale highschool cross countr' runner in the state, is co$%eting in the (estern
Maine cha$%ionshi% "he goes into the woods 7ust !efore the $ile $ark !ut
doesn8t co$e out
"he had !een struggling the entire season, feeling weak and tired, and
had dro%%ed out of three races %rior to this $eet (hat t'%e of tests would 'ou do on $il') 9 &est for a gl'cogen storage disease B &est for cardio$'o%ath' &est for dia!ete &est for ane$ia &est for
Aerobic training eects
;ncreased number of mitochondria
;ncreased hemoglobin and
hematocrit -%ercentage of red cells in !lood/ nor$all' <54=>*
?esult is increased @2 u%take and use !' tissues: VO 2 max : nor$all' A $L @2CkgC $in
JJOOAAN N BBEENNOOIIT T BBJJOORRN N DDAAEEHHLLIIEE LLAANNE E AARRMMSSTTRROONNGG 66 MMLL**KKGG**MMIIN N 2 2 MMLL**KKGG**MMIIN N CC MMLL**KKGG**MMIINN
!O
!O
""MA# O$ ELITE
MA# O$ ELITE
AEROBI% AT&LETES
AEROBI% AT&LETES
!O
!O
""MA# O$ ELITE ANIMAL
MA# O$ ELITE ANIMAL
AT&LETES
AT&LETES
PRONGHORN ANTELOPE PRONGHORN ANTELOPE 22 22 ML*KG*MINML*KG*MIN&2K- UNDER &2 MINUTESF &2K- UNDER &2 MINUTESF
uring uring endurance endurance eercise, eercise, thethe res%irator' Duotient -@
res%irator' Duotient -@22 ehaledC@ ehaledC@22 consu$ed* falls, indicating increased use consu$ed* falls, indicating increased use of fatt' acids
of fatt' acids
?E .10 for car!oh'drates?E .10 for car!oh'drates
?E. 0F0 for fats -$ore?E. 0F0 for fats -$ore
highl' reduced* highl' reduced*
%hanges in 'etabolis'
%hanges in 'etabolis'
o(er ti'e
o(er ti'e
uring endurance eercise, the res%irator' Duotient -@2 ehaledC@2 consu$ed* falls, indicating increased use of fatt' acids
;ncreased Gacet'l o9 fro$ b oidation slows !ridging reaction
ffect is decreased funneling of sugar into &9
%hanges in 'etabolis'
o(er ti'e
uring endurance eercise, the res%irator' Duotient -@2 ehaledC@2 consu$ed* falls, indicating increased use of fatt' acids
%hanges in 'etabolis'
o(er ti'e
Case Study: Paul W. is confused
Paul ( turned the corner forthe last 200 'ards of the 1==0 Boston Marathon He was well ahead of $e, ha#ing %assed $e in (ellesle' ;n the last few $inutes of the race, howe#er, he !eca$e confused 9s he %assed !' I&he Pru, he
started walking in circles He ended u% finishing 1 $inutes !ehind $e (hat went wrong for Paul ()
Case Study: Paul W. is confused
Paul ( turned the corner forthe last 200 'ards of the 1==0 Boston Marathon He was well ahead of $e, ha#ing %assed $e in (ellesle' ;n the last few $inutes of the race, howe#er, he !eca$e confused 9s he %assed !' I&he Pru, he
started walking in circles He ended u% finishing 1 $inutes !ehind $e (hat went wrong for Paul ()
(hat %ro!a!l' went wrong for Paul)
a* Lactic acid+
!* His fat stores ran out
c* His !lood sugar dro%%ed
d* arnitine deficienc'+
Brain
•Dependent on blood glucose at ~4.5 mM to
maintain ion gradients.
•Uses 20% of the total O
2 consumed by a resting
human (only 2% of the body mass)
•After several days of low glucose, switches to
use of ketone bodies, which are degraded via TCA. Conserves body’s proteins.
Heart
ardiac $uscle is aero!ic onl' with
circulating fats the %referred fuel
Lack of @2 leads to
tissue death -$'ocardial infarction*
HIH O' THE 'OLLOING PATHAYS IS INHIBITED BY THE ATION O' INSULIN
A.
GLYOLYSIS
B.
KREBS YLE.
GLUONEOGENESISD.
GLYOGEN SYNTHESISE.
'ATTY AID SYNTHESIS1. Insulin (high blood sugar)
•Insulin deficiency or resistance can lead to
The insulin receptor is a receptor tyrosine kinase (RTK).
Insulin binding triggers auto-phosphorylation at Tyr.
Epinephrine receptors act through G proteins.
3. Glucagon (low
blood sugar)
Glucagon receptor also acts through G proteins.
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The figures were found (May 2007) at http://www.wellesley.edu/Chemistry/chem227/sugars/oligo/glycogen.jpg Glycogen reu&i# e oreu&i# e
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•
2L1*ONEO2ENESIS $-ROM OALOA*ETATE OR 2L4*EROL%•
METABOLISM O- 2L4*O2EN•
,ENTOSE *4*LE•
S4NT0ESIS O- -ATT4 A*I/S•
S4NT0ESIS O- NONESSENTIAL AMINO A*I/S•
TRANSAMINATION REA*TIONS•
S4NT0ESIS O- 1REA $A ,ART 9NL8 N T:E LE4C$•
,4R1DATE /E04/RO2ENASE *OM,LE $,/0%•
INITIATION O- 2L1*ONEO2ENESIS•
b.OI/ATION O- -ATT4 A*I/S•
S4NT0ESIS O- KETONE BO/IES $ 9NL8 N T:E LE4C$•
OI/ATION /EAMINATION O- 2L1TAMATE•
TRANSAMINATION REA*TIONS•
;T47TE ;8;LE•
4ESP47T948 ;:7N $INNER MITO*0ON/RIAL MEMBRANE%•
7E49B; P:9SP:948L7T9N $INNER MITO*0 MEMBRANE%S599T: E4
•
S4NT0ESIS O- TRIA*4L2L4*EROLS AN/ ,0OS,0OLI,I/S•
ELON2ATION AN/ /ESAT1RATION O- -ATT4 A*I/S•
S4NT0ESIS O- STEROI/S•
BIOTRANS-ORMATION O- ENOBIOTI*S•
2L1*OSE.F.,0OS,0ATASE 49U<: E4 ,ROTEOS4NT0ESIS•
,OSTTRANSLATIONAL MO/I-I*ATION O-,ROTEINS•
,ROTEIN SORTIN2•
E,ORT O- ,ROTEINS $-ORMATION O-DESI*1LES%4B9S95ES
•
,ROTEOS4NT0ESISNU;LEUS
O-L8S9S95ES
•
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•
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1SE O- 04/RO2EN ,EROI/EST74EFEE ;8;LE
•
RELATIONS0I,S O- T0E METABOLI* ,AT0?A4S1N/ER DARIO1S *ON/ITIONS
•
*OO,ERATION O- DARIO1S TISS1ES•
SEE ALSO0TT,(55???7E1RNL5-225O?5*OO5BIO* 05GEN2LIS0
1$ ?ell0e state
>$ Earl
0asti# state
3$ Fasti# state
.$ Earl re0e state
;:7N<ES 9F LE4 <L8;9<EN
;9NTENT
?ELLFE ST7TE F7STN< ST7TE hormones insulin glucagon&
adrenaline& cortisol response o' the bod" gl"cemia lipogenesis proteos"nthesis gl"cemia lipol"sis ketogenesis proteol"sis
?ELLFE ST7TE F7STN< ST7TE hormones insulin glucagon&
adrenaline& cortisol response o' the bod" gl"cemia lipogenesis proteos"nthesis gl"cemia lipol"sis ketogenesis proteol"sis source o'
glucose 'rom 'ood
'rom stores $gl"cogen% gluconeogenesis 'ate o' glucose gl"col"sis
?ELLFE ST7TE F7STN< ST7TE source o'
'att" acids 'rom 'ood TA2 'rom storage TA2 'ate o' 'att" acids b.o+idation s"nthesis o' TA2 b.o+idation ketogenesis
?ELLFE ST7TE F7STN< ST7TE source o'
'att" acids 'rom 'ood TA2 'rom storage TA2 'ate o' 'att" acids b.o+idation s"nthesis o' TA2 b.o+idation ketogenesis source o'
amino acids 'rom 'ood
'rom muscle proteins 'ate o' amino acids proteos"nthesis o+idation lipogenesis gluconeogenesis
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S4NT0ESIS O- N1*LEOTI/ES $ N1*LEI*A*I/S%
•
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S8NT:ESS 9F ;T4ULLNE $1SE/ IN 1REA *4*LE%( INTAKE O- ,ROTEINS IN A /IET $-E/ STATE% OR
/E2RA/ATION O- BO/4 ,ROTEINS $STARDATION%
•
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•
KI/NE4S ( *ITR1LLINE AR2 BLOO/ LIDER
•
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•
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:
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•
TRANS,ORT O- *OENH4MES•
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59LE;ULES@
•
IN/1*TION B4 S1BSTRATE OR RE,RESSION B4 ,RO/1*T$ON T0E LEDEL O- TRANS*RI,TION%
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•
•
*ODALENT MO/I-I*ATION O- T0E*ODALENT MO/I-I*ATION O- T0E ENH4MES ENH4MES INTER*ONDERSION(INTER*ONDERSION( ,0OS,0OR4LATION5/E,0OS,0OR4LATION% ,0OS,0OR4LATION5/E,0OS,0OR4LATION% *LEADA2E O- AN *LEADA2E O- AN ,RE*1RSORE $,ROENH4ME&,RE*1RSORE $,ROENH4ME& H4MO2EN%
H4MO2EN%
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MO/1LATION O- A*TIDIT4 B4MO/1LATION O- A*TIDIT4 B4 MO/1LATORS $LI2AN/S%(MO/1LATORS $LI2AN/S%(
-EE/ BA*K IN0IBITION-EE/ BA*K IN0IBITION
3) ;:7N<E 9F 7;TT8 9F 7N
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EASTN< EN85E
P:9SP:948L7T9N /
P:9SP:948L7T9N /
EP:9SP:948L7T9N
EP:9SP:948L7T9N
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SOME ENH4MES ARE A*TIDE IN ASOME ENH4MES ARE A*TIDE IN A,0OS,0OR4LATE
,0OS,0OR4LATE/ -ORM& / -ORM& SOME ARESOME ARE
INA*TIDE
INA*TIDE
•
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,0OS,0OR4LATION(,0OS,0OR4LATION(
,ROTEIN KINASES,ROTEIN KINASES
57;49E4<; P:9SP:7TE57;49E4<; P:9SP:7TE AS A /ONOR O- AS A /ONOR O-T0E ,0OS,0ATE
T0E ,0OS,0ATE (7TPC$(7TPC$
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/E,0OS,0OR4LATION/E,0OS,0OR4LATION
The figure is found at:
The figure is found at: http://stallion.abachttp://stallion.abac.peachnet.ed.peachnet.edu/sm/kmccru/sm/kmccrae/BIOL2050/Ch1ae/BIOL2050/Ch1-13/JpegArt1-13-13/JpegArt1-13/05jpeg/05_jpeg_/05jpeg/05_jpeg_HTML/index.htmHTML/index.htm
4eGersible &oGalet 4eGersible &oGalet moi0i&atio moi0i&atio(( 7$ 7$ • • phosphor"lation b"phosphor"lation b" a
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