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Pyruvate Oxidation Pyruvate dehydrogenase complex. Aerobic Fate of Pyruvate: Overview. Mitochondria: Site of Oxidations. Pyruvate Oxidation to Acetyl-CoA. Pyruvate Dehydrogenase Complex. Complex enzyme 60 polypeptides of 3 kinds In mitocondrion matrix Regulated Inhibited by NADH and GTP - PowerPoint PPT Presentation
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Pyruvate OxidationPyruvate dehydrogenase
complex
Aerobic Fate of Pyruvate: Overview
Proteins Glycogen Fats
Glucose
Pyruvate
Acetyl-CoANADH
Citric acid(Krebs) cycle
3 NADHFADH2
CO2
CO2
GTP
Mitochondria: Site of Oxidations
Pyruvate Oxidation to Acetyl-CoA
H3C C
O
CO
O
NAD+ NADHCoASH CO2
Lipoic acid, FAD,thiamine pyrophosphate
Pyruvate dehydrogenasecomplex
H3C CO
S CoA
Pyruvate Dehydrogenase Complex
Complex enzyme– 60 polypeptides of 3 kinds
In mitocondrion matrix Regulated
– Inhibited by NADH and GTP– Stimulated by insulin
Pyruvate Dehydrogenase Complex
Three enzymes and 5 coenzymes
Enzyme Coenzyme(s) MW SubunitsEnz1 TPP 96 kDa 24Enz2 Lipoat , e CoA 70 kDa 24Enz3 FA D, NAD+ 56 kDa 12
Total MW: 4.5 x 106!
Also present: regulatory protein kinase, phosphatase
Lipoic Acid: Acyl- and Redox Carrier
S SHN
O
NH
C O
Lipoicacid
Oxidized form
Lysine
SHSH
Reduced form Acylated form
HSS
CO
CH3
On enzyme 2
Thiamine Pyrophosphate (TPP)
N
NH3C
NH2
CH2 SC
N
H
CH2H3C CH2 O P
O
O
O
P
O
O
O
H+
SC
N
H3C R2
R1TPP anion
(stable)
Pyruvate Dehydrogenase Mechanism
SC
N
H3C R2
R1
H3C C
O
CO
O H+
SC
N
H3C R2
CH3C
OH
C
O
O
R1
Pyruvate Dehydrogenase Mechanism
SC
N
H3C R2
CH3C
OH
C
O
O
R1
CO2
SC
NR1
H3C
CH3C OH
R2
Pyruvate Dehydrogenase Mechanism
SC
NR1
H3C
CH3C OH
R2
ResonanceS
CN
CH3C
OH
R1
H3C R2
Pyruvate Dehydrogenase Mechanism
SC
N
CH3C
OH
R1
H3C R2
H+
SC
N
CH3C
OH
R1
H3C R2
H
Hydroxyethyl-TPP
Pyruvate Dehydrogenase Mechanism
E1 E2 E3
TPP
C
OH
H3C HS
SFAD
E1 E2 E3
TPP
C
O
H3CHS
SFAD
Pyruvate Dehydrogenase Mechanism
E1 E2 E3
TPP
C
O
H3CHS
SFAD
CoA SH
H3C C
O
S CoA
E1 E2 E3
TPP
HS
HSFAD
Acetyl-CoA
Pyruvate Dehydrogenase Mechanism
E1 E2 E3
TPP
HS
HSFAD
E1 E2 E3
TPP
S
SFADH2
Pyruvate Dehydrogenase Mechanism
E1 E2 E3
TPP
S
SFADH2
NAD+ NADH + H+
E1 E2 E3
TPP
S
SFAD
PDH: The Overall Reaction
Acetyl-CoA enter Krebs cycle NADH passes e– to O2
H3C C
O
C
O
O
CoASH NAD+ NADH CO2
H3C C
O
S CoAPyruvate dehydrogenase
complex
-Ketoglutarate Dehydrogenase Complex
∆Gº= –33.5 kJ/mol
H2C COO
CH2
C
O
COO
H2C COO
CH2
C
O
S
Compare with pyruvate DH
-KG
CoASH CO2
NAD+
CoA
NADH
-Succinyl CoA
-Ketoglutarate Dehydrogenase Complex
Cofactors: FAD, NAD+, lipoate, TPP, CoASH Mechanism PDH complex
