The TCA Cycle
or How to Oxidize Pyruvate to
Maximize
e the Yield of
Maximiz
ATP
Maximize
of ATP
Fates of Pyruvate
Pyruvate
Other
Other Sources
Acetyl-CoA
Sources of Acetyl
Acetyl-CoA
Fates of Acetyl-CoA
Pyruvate
Deh
drogenase
Pyruvate Dehydrogenase
Dehyydrogenase
Complex
of three enzymes
pyruvate dehydrogenase
dihydrolipoyl transacetylase
dihydrolipoyl dehydrogenase
Requires CoASH, FAD, NAD+, TPP,
lipoic acid
Pyruvate
TPP
CO2
Acyl-lipoate
Pyruvate
Dehydrogenase
Dihydrolipoyl
Transacetylase
Acyl-TPP
CoASH
Lip-S
S
FADH2
+
NAD
Lip-SH
Dihydrolipoyl
Dehydrogenase
SH
Acetyl-CoA
NADH + H
+
FAD
copyright 1996 M.W.King
Reactions
ns of the TCA
Cycle
ycle
Reactio
Reactions
TCA C
Acetyl-CoA
NADH
OAA
NAD+
citrate synthase
MDH
L-Malate
Citrate
fumarase
aconitase
Fumarate
FADH2
2-step rxn:
dehydration - hydration
succinate
dehydrogenase
FAD
H2O
Isocitrate
Succinate
GTP
CoASH
IDH
NAD+
succinate thiokinase
GDP + Pi
Succinyl-CoA
NADH
CO 2
NADH
α-Ketoglutarate
NAD+
copyright 1996 M.W.King
α-KGDH
CoASH
CO 2
Regulation
Regulation of PDH
PDH
– dephosphorylation
– insulin in adipocytes
– catecholamines in
cardiac muscle
– phosphorylation
– acetyl-CoA
– NADH
P
ADP
NADH,
ATP,
acetyl-CoA
PDH
copyright 1996 M.W.King
H2O
inactive
+ve
PDH
phosphatase
PDH kinase
-ve
+ve
active
pyruvate,
NAD +,
PDH
CoASH,
ATP
ADP,
Ca +2 pyruvate + CoASH + NAD+
+2
Mg , Ca +2
P
acetyl-CoA + NADH + CO2
Citrate synthase
synthase
primarily activated by substrate
availability
inhibited by citrate and succinyl-CoA
Isocitrate dehydrogenase
dehydrogenase
α-Ketoglutarate Dehydrogenase
2+
Succinate
ogenase
Succinate Dehydrogenase
Dehydr
Dehydrogenase
i
Anapleurosis
Anapleurosis
“Filling Up” the TCA
TCA Cycle