GLIKOLISIS

Metabolism

Catabolic reactions:

Complex molecules  Simple molecules + Energy

Anabolic reactions: Biosynthetic reactions

Simple molecules + Energy (in cell)  Complex molecules

 Biosynthetic pathways

Anabolic and catabolic reactions need different energy.

Anabolic and catabolic reactions take place in different locations.

Catabolic reactions Mitochondria

Anabolic reactions Cytoplasm

 Glycolysis

Glucose is converted to two molecules of pyruvate.

An anaerobic reaction in cytoplasm.

10 Reactions
 Glycolysis

Enzymes:
PENDAHULUAN

• Glukosa merupakan komponen sentral dalam

metabolism baik di tanaman, hewan maupun
mikroorganisme
• Kaya energi potensial, sumber energi yang baik,
oksidasi sempurna menjadi CO2 dan H2O
memiliki perubahan energi bebas -2.840 kJ/mol
• Glukosa disimpan dalam bentuk polimer pati
atau glikogen
• Jika keperluan energi tinggi, glukosa dilepas dari
intraselluler dan digunakan untuk memproduksi
ATP baik secara aerobic maupun anaerobik
• Bakteri seperti E. coli menggunakan glukosa
untuk memperoleh asam amino, nukleotida,
coenzim, asam lemak dan intermediet metabolic
lain yang diperlukan untuk tumbuh
glucose memiliki 3
peranan
• Disimpan sebagai polisakarida
dan sukrosa
• Dioksidasi menjadi komponen 3
karbon (pyruvate) melalui
glikolisis untuk menyediakan ATP
dan metabolic intermediates;
• Atau dioksidasi melalui jalur
pentose phosphate
(phosphogluconate) untuk
menghasilkan ribose 5-phosphate
untuk sintesis asam nukleat dan
NADPH
PENGERTIAN GLIKOLISIS

• glycolysis (from the Greek glykys,

meaning “sweet,” and lysis, meaning
“splitting”),
• Proses pemecahan molekul glukosa
melalui serangkaian reaksi yang
dikatalisis enzim untuk menghasilkan 2
molekul 3 karbon piruvat
• Selama reaksi glikolisis, beberapa energi
bebas yang dihasilkan dari glukosa
disimpan dalam bentuk ATP dan NADH
GLIKOLISIS
• Jalur glikolisis menggambarkan proses oksidasi
glukosa menjadi piruvat dan menghasilkan ATP
dan NADH
• Disebut juga sebagai Embden-Meyerhof
Pathway
• Glikolisis adalah jalur universal yang ada pada
semua organisme dari yeast hingga mamalia
• Pada eukariot, glycolysis terjadi di cytosol
• Glycolysis merupakan proses anaerobik tidak
memerlukan oksigen
• Jika ada O2, pyruvate dioksidasi menjadi CO2
• Tanpa O2, pyruvate difermentasi menjadi lactate
or ethanol.
• Net Reaction : Glucose + 2 NAD+ + 2 Pi + 2 ADP
= 2 pyruvate + 2 ATP + 2 NADH + 2 H2O
Two phases of glycolysis
Reaction 1: phosphorylation

Hexokinase, like
many other
kinases, requires
Mg2
for its activity,

 Phosphorilasi pada C-6 menghasilkan glucose 6-phosphate, dengan ATP sebagai

phosphoryl donor
 Reaksi bersifat irreversible
 Dikatalisis oleh enzim hexokinase. Recall that kinases are enzymes that catalyze the
transfer of the terminal phosphoryl group from ATP to an acceptor nucleophile
 Akseptor hexokinase adalah hexose, normally D-glucose, meskipun hexokinase juga
dapat mengkatalisis phosphorilasi heksosa lain seperti D-fructose and D-mannose
Reaction 1: phosphorylation
 Hexokinase vs. glucokinase

Tissue-specific
isozymes.
 Reaction 2: isomerization

aldose ketose
The enzyme phosphohexose isomerase (phosphoglucose
isomerase) catalyzes the reversible isomerization
of glucose 6-phosphate, an aldose, to fructose
6-phosphate, a ketose
Reaction 2: isomerization
 Reaction 3: phosphorylation

 In the second of the two priming reactions of glycolysis,

phosphofructokinase-1 (PFK-1) catalyzes the transfer of a phosphoryl group
from ATP to fructose 6-phosphate to yield fructose 1,6-bisphosphate:
 Reaction 3: phosphorylation

Reaction 3: is another kinase reaction.

 Phosphorylasi pada gugus hidroksil C1 membentuk fructose-1,6-
bisphosphate.
 Enzyme: phosphofructokinase. This allosteric enzyme regulates the
pace of glycolysis.
 Reaction is coupled to the hydrolysis of an ATP to ADP and Pi.
 This is the second irreversible reaction of the glycolytic pathway
 Glycolysis

Overall, the first three steps of glycolysis:

1. 2 gugus phosphate ditambahkan .

2. Cincin glukosa C-6 diisomerisasi

menjadi cincin fruktosa C-5.

3. 2 ATP molecules digunakan untuk memodifikasi glucose

 Reaction 4: cleavage

The enzyme fructose 1,6-bisphosphate aldolase, often called

simply aldolase, catalyzes a reversible aldol condensation
Reaction 4: fructose-1,6-bisphosphate is split into 2 3-carbon
molecules, one aldehyde (aldose) and one ketone (ketosa): dihyroxyacetone
phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP).
Reaction 4: cleavage
Reaction 5: isomerization
Keeping Track of Carbons

G3P

glucose
Reaction 6: oxidation
Reaction 6: oxidation
Reaction 7: substrate level phosphorylation
Reaction 8: shift of phosphoryl group
Reaction 8: shift of phosphoryl group
Reaction 9: dehydration
Reaction 10: substrate level phosphorylation
 Summary

Energy
investment

Cleavage

Energy
Harvest

https://www.youtube.com/watch?v=EfGlznwfu9U
 Glycolysis

The 2 glyceraldehyde 3-phosphate units are converted into

2 pyruvate units in phase two of glycolysis.

Overall, the energy-generating phase forms 2 NADHs

and 4 ATPs.
 Glycolysis

2 ATPs are used in phase one of glycolysis, and 4 ATPs are made in phase
two of glycolysis.

The net result is the synthesis of 2 ATPs from glycolysis.

The 2 NADHs formed are made in the cytoplasm and must be

transported to the mitochondria to join the electron transport chain
and make ATP.

Overall of glycolysis
Glycolysis: Energy balance sheet

• Hexokinase: - 1 ATP
• Phosphofructokinase: -1 ATP
• GAPDH : +2 NADH
• Phsophoglycerate kinase: +2 ATP
• Pyruvate kinase: +2 ATP

• Total/ molecule of glucose: +2 ATP, +2

NADH
 Oxidative phase

•Rxns 1 and 3 produce NADPH

•Rxn 4 produces ribose-5-

phosphate

Glucose 6-P + 2 NADP+ + H2O 

Ribose 5-P + 2 NADPH + 2 H+ + CO2

From C1
 Feeder
Pathways

 All
carbohydrate
s enter
glycolysis

 In muscle,
glycerol often via
hexokinase
Glycerol 3-P
Fig 14-9
Fate of the products, pyruvate and NADH

Fig 14-
3
 Aerobic conditions

Pyruvate must diffuse across the outer and inner membrane of

mitochondria into the matrix.

The NADH formed needs O2 to return to NAD+, so without O2 no additional

pyruvate can be oxidized.
 Fermentation

Fermentation is the anaerobic conversion of glucose to ethanol and

CO2 by yeast and other microorganisms.
 1. Biosynthesis of Carbohydrates

In plants

chlorophyll
6CO
6H2 O + 6H2 O + energy C6 H12 O6 + 6H2O
2
(from Glucose
sun light)
(from sun)

Photosynthesis
 1. Biosynthesis of Carbohydrates

In animals

When both glucose and stored glycogen are depleted, glucose

can be synthesis by gluconeogenesis.
(in liver)

Intermediates of Glycolysis and Citric acid cycle are used to produce glucose.

Gluconeogenesis is not the exact reversal of glycolysis:

pyruvate to glucose does not occur by reversing the steps of glucose to pyruvate.
Fermentation in Animals
Fermentation in Yeast
Pyruvate decarboxylase reaction
Alcohol dehydrogenase reaction
Regulation of
glycolysis

Irreversible steps are

regulated:
Hexokinase/Glucokinase

Phosphofructokinase I

Pyruvate Kinase
Entry of other sugars into glycolysis
• Fructose is phosphorylated by fructokinase (liver) or
hexokinase (adipose) on the 1 or 6 positions resp.
• Fructose-6-phosphate is an intermediate of glycolysis.
• Fructose-1-phosphate is acted upon by an aldolase-like
enz that gives DHAP and glyceraldehyde.
• DHAP is a glycolysis intermediate and glyceraldehyde can
be phosphorylated to glyceraldehyde-3-P.
• Glycerol is phosphorylated to G-3-P which is then
converted to glyceraldehyde 3 phosphate.
• Galactose has a slightly complicated multi-step pathway
for conversion to glucose-1-phosphate.
• Gal--- gal-1-P ---UDP-gal 􀃆 UDP-glc 􀃆 glc-1-P.
• If this pathway is disrupted because of defect in one or
more enz involved in the conversion of gal to glc-1-P, then
galactose
• accumulates in the blood and the subject suffers from
galactosemia which is a genetic disorder, an inborn error
of metabolism.
 Glycogen
Breakdown
 Glycogen phoshorylase catalyzes the
simultaneous phosphorylation and cleavage of
an a-1,4 linked glucose from a non-reducing
end of glycogen.

 This reaction is called “phosphorolysis.”

Glycogen
Phosphorylase
 Glycogen
Breakdown
Fig 15-12
Step 1.
Glycogen
Phosphorylase

Pyridoxal phosphate

Glycogen
Phosphorylase
Berhenti pada
cabang  1-6, perlu
enzim amylo 1,6
amyloglukosidase
 Glycogen
Breakdown
Fig 15-12

Phospho-
glucomutase
 G6P fate
depends on
tissue.

 In muscle,
G6P
proceeds
through
glycolysis.

 In liver, G6P
is converted
to glucose.
Limit Dextrins
 Control of Hexokinase-01

Glucose + ATP  G6P + ADP

Feedback inhibition by
G6P.

Tissue-specific
isozymes.
hexokinase terhambat oleh akumulasi G-6-P, G-6-P tinggi tidak ada lagi permintaan
energi, maka hexokinase terhambat, dan mencegah pembentukan G-6-P
Actually, liver, the site of glycogen synthesis, has a homologous enzyme called
glucokinase. This has a high KM for glucose. This allows brain and muscle to utilize
glucose prior to its storage as glycogen
 Control of Phospofruktokinasi (PFK)-1

Many allosteric effectors; e.g., ATP.

H+,
 Control of pyruvate kinase

PEP + ADP  pyruvate + ATP

 di hati, pyruvate kinase

diaktivasi oleh Phosphoenol
pyruvate (PEP) tp dihambat
oleh ATP, AMP, sitrat dan
alanin
 Di otot, tidak diaktivasi oleh
PEP, namun dihambat oleh
phenilalanine
Karbohidrat selain glukosa
 Fruktose di phosphorilasi
pada C-1 dengan enzim
fructokinase menjadi
fructose 1 phosphate
 Fruktose 1 phosphate
dipecah menjadi
gliceraldehide dan
dihidroksiasetone
phosphate oleh fructose
1 phosphate aldose
 DHAP di konversi menjadi
gliseraldehid 3 phosphate
oleh enzim triose
phosphate isomerase
 Gliseraldehide
diphosporilasi oleh ATP
dan triosa kinase
menjadi gliseraldehid 3
phosphate
• galaktosa + ATP, oleh
enzim galactokinase
menjadi ADP dan
galaktosa 1 phosphate
• galaktose 1 phosphate
dikonversi ke epimer
karbon C4 menjadi
glukosa 1 phosphate
melalui serangkaian
reaksi dengan co enzim
uridine triphosphate
(UTP)