aerobic metabolism. summary of anaerobic glycolysis glucose + 2 adp + 2 p i 2 lactate + 2 atp + 2 h...
TRANSCRIPT
Aerobic Metabolism
Summary of Anaerobic Glycolysis
Glucose + 2 ADP + 2 Pi
2 Lactate + 2 ATP + 2 H2O + 2 H+
Energetics of Fermentation
Glucose ——> 2 Lactate
Glucose + 6 O2 ——> 6 CO2 + 6 H2O
∆Go’ = -200 kJ/mol
∆Go’ = -2866 kJ/mol
Most of the energy of glucose is still available following glycolysis!
Carbon Atom Oxidation
CH2 —> CH2OH —> C=O —> COOH —> CO2
Glucose Lactate
Figure 17-1
Oxidative Fuel Metabolism
Oxidation-Reduction Reactions:
Electron Transfer
Substrate —> NAD+ or FAD —> Electron Carriers —> O2
Electron Transport
Oxidative Phosphorylation
Figure 17-2
Citric Acid Cycle
Electron TransportOxidative Phosphorylation
ATP
H2O
ADP + Pi
Electron Transport[Proton Pumping]
Oxidative Phosphorylation
2 H+ + 1/ 2 O2Acceptor·H2
(NADH or FADH2)
Acceptor(NAD+ or FAD)
Substrate(oxidized)
Substrate·H2
(reduced)
Oxidized e– carrier
Reduced e– carrier
Etc.2 e–
Electron TransportOxidative Phosphorylation
Summary of Citric Acid Cycle
Acetyl-CoA + 3 NAD+ + FAD + GDP + Pi
2 CO2 + 3 NADH + 3H+ + FADH2 + GTP + CoA-SH
Pyruvate Dehydrogenase:
Synthesis of Acetyl-CoA
Acetyl-CoA
Thioester
Sources of Acetyl-CoA
• Carbohydrates (sugars via glycolysis)
• Fats (fatty acids)
• Proteins (amino acids)
Pyruvate Dehydrogenase(Formation of Acetyl-SCoA)
CH3 C COOH
O
CH3 C S
O
CoACoenzymeA SH
Acetyl–SCoAPyruvate
+ CO2
NADH + H+
+
NAD+
Oxidative Decarboxylation
Pyruvate Dehydrogenase(Multienzyme Complex)
• E1: Pyruvate Dehydrogenase or Pyruvate Decarboxylase
• E2: Dihydrolipoyl Transacetylase
• E3: Dihydrolipoyl Dehydrogenase
Multienzyme Complexes
• Enhanced reaction rates
• Channeling of reaction intermediates
• Coordinate regulation
Figure 17-3a
Electron Micrograph of E. coli Pyruvate Dehydrogenase
Organization of E. coli Pyruvate Dehydrogenase Complex
Pyruvate Dehydrogenase(Mammalian Enzyme)
• E1, E2, and E3
• E3 binding protein
• Kinase (regulation)
• Phosphatase (regulation)
Table 17-1
Coenzymes and Prosthetic Groups of Pyruvate
Dehydrogenase
Thiamin Pyrophosphate
N
N
CH3
CH2 NS
CH3
CH2 CH2 O P O P O –
O O
O – O –NH2
Thiamin Pyrophosphate
N
N
CH3
CH2 NS
CH3
CH2 CH2 O P O P O –
O O
O – O –NH2
Lipoic Acid
HOOC (CH2)4
S S
Figure 17-7
Reduction of Lipoamide
E2
E2
Coenzyme A
HS CH2 CH2 NH C
O
CH2 CH2 NH C
O
CH
OH
C
CH3
CH3
CH2 OADP( 3'P)
Pantothenic Acid (vitamin B5)
NAD+
N
OCH2
OH OH
O
OCH2
OH OH
AOP
O
O–
P
O
O–
O
CNH2
O
Nucleotide
Nucleotide
Figure 14-12
Flavin Adenine Dinucleotide (FAD)
Reduction of FAD
N
N
N
NH
H3C
H3C O
O
CH2
CHOH
CHOH
CHOH
CH2OADP
N
N
N
NH
H3C
H3C O
O
CH2
CHOH
CHOH
CHOH
CH2OADP
H
H
2 H·
FADH2FAD
Pyruvate Dehydrogenase(Formation of Acetyl-SCoA)
CH3 C COOH
O
CH3 C S
O
CoACoenzymeA SH
Acetyl–SCoAPyruvate
+ CO2
NADH + H+
+
NAD+
Oxidative Decarboxylation
Overall Reaction ofPyruvate Dehydrogenase
Reaction order of Pyruvate Dehydrogenase
Mechanism of Pyruvate Dehydrogenase
(Decarboxylation of Pyruvate)
Same mechanism as Pyruvate Decarboxylase
CH3C OH
E1–TPP
+ E1–TPP
CH3C COOH
O
C
O O–
CO2
CH3C OH
E1–TPP
Pyruvate
Page 572
Mechanism of Decarboxylation of Pyruvate
Remainderof Reaction
Reaction order of Pyruvate Dehydrogenase
Mechanism of Pyruvate Dehydrogenase
(Hydroxyethyl Group Transfer)
CH3C OH
E1–TPPE2
S S
E2
S SH
C OH3C
+ E1–TPP+
H+
Forms of Lipoamide
Page 574
Mechanism of Hydroxyethyl Group Transfer
Reaction order of Pyruvate Dehydrogenase
Mechanism of Pyruvate Dehydrogenase
(Transesterification)
E2
SH SH
E2
S SHH3C C
O
SCoAC O
H3C
+CoA–SH+
Page 574
Mechanism of Transesterification
Reaction order of Pyruvate Dehydrogenase
Mechanism of Pyruvate Dehydrogenase
(Reoxidation of Dihydrolipoamide)
E2
SH SH
E2
S S
E3–FADH2+E3–FAD+
Mechanism of Pyruvate Dehydrogenase
(Oxidation of E3–FADH2)
E3–FADH2 + NAD+ ——> E3–FAD + NADH + H+
Page 574
Mechanism of Reoxidation of Dihydrolipoamide
Page 574
Mechanism of Oxidation of E3–FADH2
Short Lived
Page 575
A Swinging Arm Transfers Intermediates
E2
Organization of E. coli Pyruvate Dehydrogenase Complex
Pyruvate Dehydrogenase(Formation of Acetyl-SCoA)
CH3 C COOH
O
CH3 C S
O
CoACoenzymeA SH
Acetyl–SCoAPyruvate
+ CO2
NADH + H+
+
NAD+
Oxidative Decarboxylation
Regulation of Pyruvate Dehydrogenase
• Product Inhibition (competitive)– NADH– Acetyl-SCoA
• Phosphorylation/Dephosphorylation– PDH Kinase: inactivation– PDH Phosphatase: activation
Regulation of PDH Kinase(Inactivates PDH by phosphorylation)
• Activators of PDH Kinase– NADH– Acetyl-SCoA
• Inhibitors of PDH Kinase– Pyruvate– ADP– Ca2+ (high Mg2+)– K+
Regulation of PDH Phosphatase
(Activates PDH by Dephosphorylation)
• Activators of PDH Pase– Insulin– Mg2+
– Ca2+