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Oksidasi Asam Piruvat dan PDH

1. Pyruvate enters the mitochondria and is converted to acetyl-CoA through a 3 step oxidation process catalyzed by the pyruvate dehydrogenase complex. 2. The pyruvate dehydrogenase complex is a multi-enzyme complex that requires five co-factors and contains three enzymes that work together to irreversibly convert pyruvate to acetyl-CoA. 3. The conversion of pyruvate to acetyl-CoA produces carbon dioxide and reduces NAD+ to NADH, and is regulated through feedback inhibition and phosphorylation/dephosphorylation of the enzymes in the complex.

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238 views14 pages

Oksidasi Asam Piruvat dan PDH

1. Pyruvate enters the mitochondria and is converted to acetyl-CoA through a 3 step oxidation process catalyzed by the pyruvate dehydrogenase complex. 2. The pyruvate dehydrogenase complex is a multi-enzyme complex that requires five co-factors and contains three enzymes that work together to irreversibly convert pyruvate to acetyl-CoA. 3. The conversion of pyruvate to acetyl-CoA produces carbon dioxide and reduces NAD+ to NADH, and is regulated through feedback inhibition and phosphorylation/dephosphorylation of the enzymes in the complex.

Uploaded by

adelia salsabila
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OKSIDASI ASAM PIRUVAT

Prof. Dr. Suhartati, dr., MS.


Oksidasi Piruvat terjadi di matriks mitokondrial

Sitosol
irreversible
mitochodria.

COO - NAD+ NADH + H + O


C O + HSCoA H3C C ~SCoA + CO2
Pyruvate
CH3 dehydrogenase
complex
pyruvate Acetyl CoA
SIKLUS OKSIDASI PIRUVAT

• Pyruvate enters mitochondri


– 3 step oxidation process
– releases 1 CO2 (count the carbons!)
– reduces 2 NAD  2 NADH (moves e-)
– produces acetyl CoA

• Acetyl CoA enters Krebs cycle


Enzim PDH Kompleks

• Multi-enzim kompleks
– 3 enzim
– 5 Ko-enzim
Enzim PDH Kompleks
Piruvat Dehidrogenase Kompleks
membutuhkan 5 ko-faktor :
• TPP
• Lipoamida
• KoA,
• FAD HSCoA
• NAD+,

piruvat dehidrogenase NAD+


dihidrolipoil dehidrogenase

dihidrolipoil transasetilase
Summary PDH
PDH is a multienzyme complex that needs five co-factors
(CoA, NAD+, TPP, Lipoamide, FAD )
The structure of
pyruvate dehydrogenase complex
CO2

NADH
+H+

NAD+
CoASH
Regulasi PDH
Irreversible
Ratio ATP/AMP important

allosteric inhibitors: allosteric activators:


ATP, acetyl CoA, AMP, CoA,
NADH, FA NAD+,Ca2+

Pyruvate dehydrogenase
(active form)

Pi ATP

pyruvate dehydrogenase pyruvate dehydrogenase


phosphatase kinase
H2O ADP

pyruvate dehydrogenase P acetyl CoA, ADP,


Ca2+,insulin (inactive form) NADH NAD+
Regulasi PDH
OTOT
• Istirahat
(tidak dibutuhkan)
– Status energi tinggi
– NADH & Asetik KoA tinggi
• Inaktivasi PDH
– Hi ATP & NADH & AcCoA
• PDH dihambat
• Latihan (dibutuhkan)
– NADH, ATP, Asetil KoA rendah
Regulasi PDH
Liver

• Makan (dibutuhkan untuk


sintesis FA)
– Insulin aktivatkan PDH

• Lapar (tidak dibutuhkan)


– No insulin
• PDH inaktiv
Acetyl CoA
CoASH
Pyruvate feedback inhibits E2

E1 feedback inhibits E3
E2
E3
NADH
CO2

NAD+

GAMBAR Allosteric feedback inhibition of E2 by acetyl CoA and E3 by


NADH
Figure Regulation of NAD+
CoASH
E1 by covalent ACTIVE ENZYME
Pyruvate
modification through E3
E2
phosphorylation
E1 NADH

CO2 Acetyl CoA

OH
activate PDH kinase
Pi ATP
PDH PDH Kinase
Phosphatase
+ inhibit PDH kinase
ADP
CoASH NAD+
Pyruvate
Ca++ E1
E3
Insulin E2
OPO4 INACTIVE ENZYME
Conversion of pyruvate to acetyl-CoA
• Oxidative decarboxylation
– Series of 5 reactions
– Irreversible
– Mechanism is highly complicated
• Catalyzed by complex of enzymes and cofactors
– Pyruvate dehydrogenase complex
– Multi-enzyme structure located
in mitochondrial matrix
– Contains multiple copies of three
non-covalently associated enzymes
and five coenzymes
– E1 and E3 surround core of 24-60 E2 chains
(# chains depends on type of cell)
• Overall reaction:
CH3C(O)CO2- + NAD+ + CoASH → CH3C(O)-SCoA + NADH + CO2

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