Metabolisme

PowerPoint Lectures for

Roya Suffah
Biology, Zain.,
Seventh EditionM.Si.
Neil Campbell and Jane Reece

Lectures by Chris Romero

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 Jalur-jalur Metabolisme

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 Metabolisme
Definisi
Keseluruhan reaksi kimia yang terjadi di dalam tubuh
organisme, terjadi karena adanya interaksi antar molekul

Penyusunan Senyawa Kimia dalam Jalur Metabolisme

✔ Dimulai dengan molekul spesifik sebagai substrat, metabolit

antara, dan diakhiri dengan produk akhir
✔ Masing-masing proses dikatalisasi dengan bantuan enzim
Enzyme Enzyme Enzyme
1 2 3
A B C D
Reaction Reaction Reaction
Starting 1 2 3 Produc
molecul t
e
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 Jenis-jenis metabolisme

Metabolisme

Katabolisme Anabolisme

Perombakan molekul Pembentukan molekul

organik kompleks organik kompleks dari
menjadi molekul molekul anorganik
anorganik sederhana sederhana
Menggunakan energi
Melepaskan energi

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Energi
– Dapat menyebabkan perubahan
– Dalam berbagai bentuk, beberapa dapat digunakan untuk melakukan kerj
– dapat diubah dari suatu bentuk menjadi bentuk yang lain

Beberapa Jenis Energi :

• Energi Kinetik
Energi yang berasosiasi dengan gerak
• Energi Potensial
Tersimpan pada lokasi tertentu, pada material tertentu
• Energi kimia
tersimpan pada struktur molekul tertentu

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 Hukum Transformasi Energi
Termodinamika : studi transformasi energi
• Hukum Termodinamika I
– Energi tidak dapat diciptakan atau
dimusnahkan
– Energi dapat dipindahkan atau diubah
bentuknya

• Hukum Termodinamika II
– Perubahan spontan tidak memerlukan energi,
dapat meningkatkan nilai entropi (ketidakberaturan)

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 Energi pada Reaksi-reaksi metabolisme : ATP
• ATP berperan sebagai energi penghubung untuk reaksi
eksergonik dan reaksi endergonik
• Energi penghubung (ATP) : Merupakan cara agar sel dapat
mengatur aliran energi
• ATP (adenosine triphosphate) Menyedikan energi untuk
fungsi sel
Adenine NH2

N C
C N
O O O HC
CH
C
-O N
O O O CH2 N
O
O- O- O-
H H
Phosphate groups H H Ribose
Figure 8.8 OH OH

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Cara ATP menyediakan Energi?

Drive the regeneration of ATP from ADP

and phosphate

ATP synthesis from ATP hydrolysis to

ADP + P i requires energy ADP + P i yields energy

ATP

Energy from catabolism Energy for cellular work

(exergonic, energy yielding (endergonic, energy-
processes) consuming processes)
ADP + P i
Figure 8.12

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 Cara ATP menyediakan Energi?
• Energi dilepaskan dari ATP
– Saat ikatan fosfat terlepas

P P P

Adenosine triphosphate (ATP)

H2O

P i
+ P P Energy

Figure 8.9 Inorganic phosphate Adenosine diphosphate (ADP)

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Konvergen
Divergen

Lingkar
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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
 Persamaan Reaksi Respirasi Seluler

• Selama respirasi seluler, glukosa dioksidasi

dan oksigen direduksi

becomes oxidized

C6H12O6 + 6O2 6CO2 + 6H2O + Energy

becomes reduced

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 Tahapan Respirasi Seluler

– Glikolisis
– Siklus Asam Sitrat (siklus Krebs)
– Fosforilasi Oksidatif

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 • Glikolisis
– Proses pemecahan glukosa menjadi 2 molekul
asam sitrat
• Siklus Asam Sitrat
– Tahap utama pemecahan glukosa

• Fosforilasi Oksidatif
– Berjalan berdasarkan rantai transfer elektron
– Menghasilkan banyak ATP

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 Electrons Electrons carried
carried via NADH and
via NADH FADH2

Oxidative
Citric phosphorylation:
Glycolsis
acid electron
Glucose Pyruvate cycle transport and
chemiosmosis

Cytosol
Mitochondrion

ATP ATP ATP

Substrate-level Oxidative
Substrate-level
phosphorylation phosphorylation
phosphorylation
Figure 9.6

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 Glikolisis
• Terdiri dari 2 fase:
Glycolysis
– Fase investasi
Citric Oxidative
acid phosphorylation
cycle

energi
ATP ATP ATP

– Fase Energy investment

phase

menghasilkan Glucose

energi 2 ATP + 2 P 2 ATP used

Energy payoff phase

4 ADP + 4 P 4 ATP formed

2 NAD+ + 4 e- + 4 + 2 H+
H+ 2 NADH

2 Pyruvate + 2 H2O

4 ATP formed – Glucose 2 Pyruvate + 2 H2O

2 ATP used
2 ATP + 2 H+

2 NAD+ + 4 e– + 4 H + 2 NADH
Figure 9.8

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 Glikolisis

Tahap 1 :
Investasi Energi (ATP). Terjadi
phosphorilasi glukosa. Ion negatif
melimpah didalam sel, glukosa jadi
kurang stabil.

Stage 2 : Pemisahan 1 molekul

dengan 6-Karbon menjadi 2
molekul dengan masing-masing
3 karbon

Stage 3 : Tahap Menghasilkan Energi

(ATP). Oksidasi terhadap frgamen
3-karbon menghasilkan ATP

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Triose phosphate isomerase

All the DHAP is converted to glyceraldehyde ΔG°’ = 1.8 kcal mol-1

3-phosphate. Although, the reaction is
reversible it is shifted to the right since
glyceraldehyde 3-phosphate is a substrate for
the next reactions of glycolysis. Thus, both
3-carbon fragments are subsequently oxidized.

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The fate of glyceraldehyde 3-phosphate

Glyceraldehyde 3-phosphate DH

Stage 3: The energy yielding phase.

ΔG°’ = 1.5 kcal mol-1

An aldehyde is oxidized to
carboxylic acid and inorganic
phosphate is transferred to form 1,3-BPG has a high
phosphoryl-transfer potential.
acyl-phosphate. NAD+ is reduced
It is a mixed anhydride.
to NADH.

Notice, under anaerobic conditions NAD+ must be re-supplied.

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 In the liver,
when fructose
enters glycolysis
the PFK
reaction is
bypassed.

Fructose metabolism in
the liver

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Galactose is converted
to glucose-6P via a
four step reaction
involving UDP-glucose

Hexokinase

Fructokinase

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 In Summary

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 CH2OH
H H H Citric
Glycolysis Oxidative
HO H acid
phosphorylation
HO OH
H OH cycle
Glucose
ATP 1
Hexokinase
ADP
CH2OH P
H H O H
OH H
HO
H OH
Glucose-6-phosphate
2
Phosphoglucoisomerase
CH2O P
O CH2OH
H HO
H HO
HO H
Fructose-6-phosphate
ATP 3
Phosphofructokinase
ADP
P O CH2 O CH2 O P
HO
H OH
HO H
Fructose-
1, 6-bisphosphate 4
Aldolase

5 H
P O CH2 Isomerase C O
C O
CHOH
CH2OH
CH2 O P
Dihydroxyacetone Glyceraldehyde-
Figure 9.9 A phosphate 3-phosphate

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 6
2 NAD+
Triose phosphate dehydrogenase
2 NADH 2 Pi
+ 2 H+
2
P O C
O
CHOH
CH2 O P
1, 3-Bisphosphoglycerate
2 ADP 7
Phosphoglycerokinase
2 ATP

2 O–
C
CHOH
CH2 O P
3-Phosphoglycerate
8
Phosphoglyceromutase
2 O–
C O
H C O P
CH2OH
2-Phosphoglycerate
9
2 H2O Enolase
–
2 O
C O
C O P
CH2
Phosphoenolpyruvate
2 ADP 10
Pyruvate kinase
2 ATP

2 O–
C O
C O
Figure 9.8 B CH3
Pyruvate
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 Piruvat menjadi Asetil CoA (Dekarboksilasioksidatif)
Sebelum Siklus Asam Sitrat, piruvat harus diubah menjadi
asetil coA

What Happenned? MITOCHONDRION

CYTOSOL

✔ Dekarbosilasi NAD
NAD+ + H+
(penghilangan gugus –
H
O Co
COO, dilepas dalam S
A
2
bentuk CO2), C O
✔ Fragmen sisa yang terdiri C O
dari 2 karbon dioksidasi, C O
hasilnya : ion Asetat CH3
✔
1 3
Pengikatan Co-Enzim A
CH3 Acetyle
(molekul turunan vitamin CoA
Coenzyme
B yang mengandung Pyruvate CO2
A
atom S) oleh ion Asetat,
Hasilnya : AsetilCoA Transport protein

Figure
9.10

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 Siklus Asam Sitrat (Siklus Krebs)

Pyruvate Glycolysis Citric Oxidative

acid
(from glycolysis, cycle phosphorylation

2 molecules per glucose)

ATP ATP ATP

CO2

CoA
1 kali terjadi
NADH Dekarboksilasi
+ 3 H+ Acetyle CoA
CoA

CoA

Citric 2 kali terjadi

acid 2 CO2 Dekarboksilasi
cycle
FADH2 3 NAD+

FAD 3 NADH
+ 3 H+
ADP + Pi Oksidasi
ATP
Figure 9.11
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 1
CoA lepas, gugus Asetat kemudian
Glycolysis Citric acid Oxidative
cycle
phosphorylation berikatan dengan oksaloasetat
menghasilan ion sitrat

S CoA
C O
2
8 Oksidasi Dehidrogenasi Ion sitrat berubah menjadi
Ion malat dioksidasi CH3 isomernya : ion isositrat
menghasilkan kembali ion Acetyl CoA dengan melepaskan dan
oksaloasetat CoA SH menangkap kembali H2O

NADH O C COO–
+ H+ CH2 1 COO– H2O
Hidrasi 7 COO – CH2 COO–
NAD+ 3 Dehidrogenasi
Hidrasi pada ion fumarat 8 HO C COO –
CH2
Oxaloacetate 2
mrnghasikan ion malat CH2 HC COO– isositrat
COO–
COO –
HO CH mengalami
HO CH Malate
COO– dekarboksilasi,
CH2 Citrate
Isocitrate fragmen sisanya
COO– Figure 9.12 kemudaian
Citric CO2 dioksidasi. Hasil :
acid 3 α-Ketoglutarate
7 cycle NAD+
H2O
Dehidrogenasi
COO– NADH
COO–
6 Oksidasi CH
Fumarate CH2
+ H+
Ion suksinat dioksidasi, 2 HC CoA SH
CH2
atom H dilepaskan dan COO –
Succinyl
ditransfer ke molekul FAD CoA C O
6 4 –
membentuk FADH2. sisa COO– CoA SH COO – COO α-Ketoglutarate
fragmen : ion fumarat CH2 5 CH2
FADH2 CO2
CH2 CH2 NAD+
FAD
COO– C O 4 Dehidrogenasi
Succinate Pi S CoA NADH
GTP GDP + H+ Hasil dekarboksilasi oksidatif 2
5 kemudian berikatan dengan
CoA digantikan oleh gugus fosfat. Yang tak lama CoA menjadi Suksinil CoA
ADP
kemudian ditransfer pada molekul GDP membentuk
GTP kemudian ke ADP sehingga dihasilkan ATP. ATP
Sisa fragmen : ion suksinat
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 Fosforilasi Oksidatif
Chemiosmosis dan rantai transfer elektron
Inner
Mitochondrial
Oxidative
phosphorylation.
membrane
Glycolysis Citric acid
cycle electron transport
and chemiosmosis

ATP ATP ATP

H+
+
H

H+
H+
Cyt c
Protein complex
Intermembrane of electron
space carners
Q IV
I III
ATP
Inner II synthase
mitochondrial H2O
FADH2
membrane FAD+ 2 H+ + 1/2 O2
NADH+ NAD+ ADP + Pi ATP
(Carrying electrons
from, food) H+
Mitochondrial
Electron transport chain Chemiosmosis
matrix
Electron transport and pumping of protons (H+), ATP synthesis powered by the flow
which create an H+ gradient across the membrane Of H+ back across the membrane

Figure 9.15 Oxidative phosphorylation

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 Ringkasan
Electron shuttles MITOCHONDRION
CYTOSOL 2 NADH
span membrane
or
2 FADH2

2 NADH 2 NADH 6 NADH 2 FADH2

Glycolysis Oxidative
2 Citric phosphorylation:
2 Acetyl acid electron transport
Glucose Pyruvate CoA cycle and
chemiosmosis

+ 2 ATP + 2 ATP + about 32 or 34 ATP

by substrate-level by substrate-level by oxidative phosphorylation, depending
phosphorylation phosphorylation on which shuttle transports electrons
from NADH in cytosol

About
Maximum per glucose: 36 or 38 ATP

Figure 9.16

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 Proses Input Output
Glikolisis Glukosa 2 As. Piruvat
(sitoplasma) 2 NADH
2 ATP
Dekarboksilasi Oksidatif 2 as. piruvat 2 asetil Co-A
(matriks mitokondria) 2 CO2
2 NADH
Siklus Krebs 2 asetil Co-A 4 CO2
(matriks mitokondria) 6 NADH
2 FADH2
2 ATP
Fosforilasi Oksidatif 10 NADH 34 ATP
(membran dalam 2 FADH2 6 H 2O
mitokondria)

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 Respirasi Anaerob (tanpa menggunakan oksigen)
2
2 ADP + 2 P1 ATP O–
C O
Glucose Glycolysis C O C6H12O6 (Glukosa) ⮀ 2
CH3
2 Pyruvate
C2H6O (Etanol) + 2 CO2 + 2
2 NAD+ 2 NADH 2 CO2 ATP
H H
H C OH C O
CH3 CH3
2 Ethanol 2 Acetaldehyde
(a) Alcohol fermentation

2
2 ADP + 2 P1 ATP

Glucose Glycolysis O–
C O
C6H12O6 (Glukosa) ⮀ 2
2 NAD+ 2 NADH
C O C3H6O3 (As. Laktat) + 2 ATP
O CH3
C O
H C OH
CH3
2 Lactate
(b) Lactic acid fermentation
Figure 9.17
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 Glukoneogenesis

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 Glukoneogenesis
• Glukoneogenesis : proses sintesis glukosa dari
prekursor nonkarbohidrat

Why
•?
Cadangan glukosa menyusut ketika kelaparan atau
puasa seharian
• Otak bergantung pada glukosa (120g/d) sebagai sumber
energi, sehingga glukosa perlu disintesis dari molekul
selain karbohidrat.

PYRUVATE → GLUCOSE

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 Gluconeogenesis: Pyruvate → Glucose

Enzim yang ditulis dengan warna

merah adalah yang bertindak dalam
glukoneogenesis. Enzim-enzim
tersebut menghasilkan energi bebas
yang sangat negatif untuk rekasi
glikolisis yang irreversibel.

Enzim yang ditulis dengan warna biru

adalah yang terlibat dalam kedua
jalur.

Molekul Glukogenik :
Molekul senyawa yang dapat diubah
menjadi piruvat

Eg :
Alanin, laktat dan gliserol

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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
 Glycolysis and
gluconeogenesis are
reciprocally regulated
Insulin stimulates Glucagon stimulates

A high [AMP] indicates

that the energy charge
is low and signals the
need for ATP.

High [ATP] and [citrate]

indicate the energy
charge is high and
intermediates are
abundant.

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 The Cori Cycle

Lactate from active muscle is converted to glucose in liver.

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 Lactate and alanine are glucogenic

• In muscle alanine is produced from pyruvate by

transamination.
pyruvate + glutamate ⮀ alanine + α-ketoglutarate

• In the liver alanine is converted back to

pyruvate.
• In active muscle lactate builds up, passes
through the blood and is converted to pyruvate
in the liver.
• Thus, part of the metabolic burden of active
muscle is shifted to the liver.

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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings