GLUKONEOGENESIS

DEFENISI
• Lintasan reaksi untuk mengubah :
Senyawa-senyawa non karbohidrat menjadi glukosa
atau glikogen.

• Substrat utama glukoneogenesis :

. Asam-asam amino glukogenik (masuk di piruvat)
. Laktat ( konversi ke piruvat)
. Gliserol (masuk di gliserol 3 fosfat).
. Propionat pada hewan ruminansia (masuk di
suksinil Ko-A)

•
Glukosa merupakan sumber tenaga
utama untuk otak, jaringan syaraf, testes,
eritrosit dan medula ginjal.
 • Kebutuhan glukosa setiap hari : 160 grams.
• Setelah penyerapan zat makanan kadar glukosa
darah manusia dan mamalia lain 4,5 – 5,5 mmol/L
dan akan naik setelah konsumsi KH 6.5 -7.2 .
• Selama puasa kadar glukosa darah turun menjadi
3.3.- 3.9 mmol/L.
• Lebih kurang, 20 grams glukosa terdapat pada cairan dan
hampir 190 grams disimpan sebagai glikogen.

• Jaringan utama tempat reaksi glukoneogenesis:

. Hati
. Ginjal
Reaksi Glukoneogenesis meliputi:
• Glikolisis
• Siklus Asam sitrat
• Beberapa reaksi khusus
REAKSI GLIKOLISIS
SIKLUS KREB
JALUR SINTESIS GLUKOSA DARI PREKURSOR UTAMA GLUKONEOGENESIS
YANG MERUPAKAN KEBALIKAN REAKSI GLIKOLISIS
SIKLUS CORI (CORI CYCLE)/SIKLUS ASAM LAKTAT
TUGAS V.

1. Cari asam asam amino yang tergolong asam amino glukogenik yaitu asam
amino yang dapat di ubah menjadi glukosa.

2. Ceritakan dengan gambar bagaimanakah reaksi by pass pada reaksi

glukoneogenisi untuk merubah

- Piruvat menjadi phosphoenol piruvat

- Fruktosa 1,6 bipospat menjadi fruktosa 6 pospat
- Glukosa 6 pospat menjadi glukosa 1 pospat
 KONTROL UTAMA PENGATURAN
GLIKOLISIS DAN GLUKONEOGENESIS
 Masuknya Noncarbohydrat Precursors

Piruvat Glukosa HK Note places of entry

of noncarbohydrate
precursors.
7 lintasan reaksi
glukoneogenesis merupakan PFK

kebalikan reaksi glikolisis

3 tahap reaksi pada glykolisis

merupakan reaksi irreversible
(satu arah) Oleh sebab itu tidak
dapat digunakan pada reaksi
glukoneogenesis

Dan Oleh sebab itu pula

dibutuhkan 3 step reaksi by pass PK
untuk menggantikan
reaksi tsb.
 First Bypass Reaction: Convervsion of Pyruvate to
Phosphoenolpyruvate

Requires participation of both mitochondrial and cytosolic enzymes.

Step 1: Pyruvate is transported from the cytosol into mitochondria via

the mitochondrial pyruvate transporter OR pyruvate may be generated
within mitochondria via deamination of alanine.

Step 2: Pyruvate is converted to OAA by the biotin-requiring enzyme

pyruvate carboxylase as follows:

Pyruvate + HCO3- + ATP oxaloacetate + ADP + Pi + H+

Pyruvate carboxylase is a regulatory enzyme. Acetyl CoA is a

positive effector.
 Malate/α-KG
transporter

Mitochondria are the

Mitochondrial
source of reducing Malate dehydrog.
equivalents that will
be needed later.

Pyruvate
transporter

Produced in muscle
Or RBCs
Step 3: Oxaloacetate is reduced to malate by mitochondrial malate
dehydrogenase at the expense of mitochondrial NADH.

Oxaloacetate + NADH + H+ L-malate + NAD+

Step 4: Malate exits the mitochondrion via the malate/α-

ketoglutarate
carrier.

Step 5: In the cytosol, malate is reoxidized to oxaloacetate via

cytosolic malate dehydrogenase with the production of cytosolic
NADH.

L-malate + NAD+ oxaloacetate + NADH + H+

Step 6: Oxaloacetate is then converted to phosphoenolpyruvate (PEP)
by phosphoenolpyruvate carboxykinase in the reaction:

Oxaloacetate + GTP phosphoenolpyruvate + CO 2 + GDP

The overall equation for this set of bypass reactions is:

Pyruvate + ATP + GTP + HCO3-

phosphoenolpyruvate + ADP + GDP + Pi + H+ + CO2

Thus the synthesis of one molecule of PEP requires an investment

of 1 ATP and 1 GTP.

Note: when either pyruvate or the ATP/ADP ratio is high, the reaction
is pushed toward the right (i.e., in the direction of biosynthesis).
When lactate is the gluconeogenic precursor (e.g. after vigorous
exercise) an abbreviated pyruvate to PEP bypass is utilized.

Important Point: Conversion of lactate to pyruvate (via LDH) in the

cytosol yields NADH which is essential for gluconeogenesis to
proceed (i.e., NADH is needed at the glyceraldehyde 3-phosphate
dehydrogenase step). Thus, the export of malate from mitochondria
is no longer necessary as a source of NADH. In the abbreviated
pathway:

Step 1: Pyruvate is transported into mitochondria on the pyruvate

transporter.

Step 2: Within mitochondria pyruvate is converted to OAA (via

pyruvate carboxylase).

Step 3: Intramitochondrial oxaloacetate is converted to PEP (via a

mitochondrial form of PEP carboxykinase).

Step 4: PEP is transported out of mitochondria and continues up the

gluconeogenic pathway.
 Malate/α-KG
transporter

Mitochondria are the

source of reducing Mitochondrial
Malate dehydrog.
equivalents that will
be needed later.

Pyruvate
transporter

Produced in muscle
or RBCs
 Glucose

Glucose 6-phosphate
Fructose 6-phosphate

Fructose 1,6-bisphosphate

PEP

Pyruvate
 Second Bypass Reaction: Conversion of Fructose
1,6-
bisphosphate to Fructose 6-phosphate

The second glycolytic reaction (i.e., the phosphorylation of fructose

6-phosphate by PFK1) is irreversible.

Hence, for gluconeogenesis fructose 6-phosphate must be generated

from fructose 1,6-bisphosphate by a different enzyme:
fructose 1,6-bisphosphatase.

This reaction is also irreversible.

Fructose 1,6-bisphosphate + H2O fructose 6-phosphate + Pi

ΔG˚’ = -3.9 kcal/mol

PROSES GLIKOLISIS DAN GLUKONEOGENESIS
 Alanin
Treonin Piruvat
Glisin
Serin CO2 Arginin
Sistein Histidin
Asetil-KoA 2H Glutamin
Prolin
Asetoasetil-KoA
Oksaloasetat Sitrat

Fenil Alanin Isositrat Glutamat

Malat Citric acid
Tirosin cycle
CO2
Leusin Fumarat
Lisin α- Ketoglutarat
2H 2H
Triptofan CO2 Isoleusin
2H Metionin
Suksinate
Suksinil KoA Valin
Aspartat
Asparagin 2H GTP
NADH
ADP + Pi
2e -

NADH
dehidrogenase
2e- 1 ATP

Ubikuinon
2e- ADP +Pi
Transport
Elektrom Sitokrom b
Fosforilasi 2e-
oksidatif Sitokrom c1 1 ATP
2e_
Sitokrom c
2e- ADP + Pi
Sitokrom
Osidasi a a3
2e- 1 ATP
2H+ + ½02 H2O
 Glucose

Glucose 6-phosphate
Fructose 6-phosphate

Fructose 1,6-bisphosphate

PEP

Pyruvate