Professional Documents
Culture Documents
28 CitrateCycle 2008 (Reparado)
28 CitrateCycle 2008 (Reparado)
• The citrate cycle is a "metabolic engine" in which all eight of the cycle
intermediates are continually replenished to maintain a smooth-running
energy conversion process. The fuel for this metabolic engine is acetyl-
CoA, the exhaust is two molecules of CO2, and the energy output is
redox energy used in the electron transport system for ATP synthesis.
In addition, 1 GTP is
produced by
substrate level
phosphorylation
which is converted to
ATP by nucleotide
kinase.
All of the enzymes in the
citrate cycle, electron
transport chain and
oxidative
phosphorylation reside in
the mitochondrial matrix
where pyruvate is
converted to acetyl-CoA
by the enzyme pyruvate
dehydrogenase.
The "currency exchange" for
redox energy and ATP
synthesis in the mitochondria
electron transport chain is ~2.5
ATP/ NADH. Oxidation of 2
FADH2 molecules by the
electron transport chain results
in only ~3 molecules of ATP
(~1.5 ATP/FADH2) because of
differences in where these two
coenzymes enter the electron
transport chain.
Citrate synthase – catalyzes the first reaction in the pathway and can
be inhibited by citrate, succinyl-CoA, NADH and ATP; inhibition by
ATP is reversed by ADP.
Pathway Questions
What are the key regulated enzymes in citrate cycle?
Purified
citrate is a
food
additive
The complete oxidation of glucose to CO2 and H2O
is summarized by the reaction:
This coupled redox reaction directly links the citrate cycle to the electron
transport system through the redox conjugate pair FAD/FADH2 which is
covalently linked to the enzyme succinate dehydrogenase, an inner
mitochondrial membrane protein.
Oxidation of succinate results in the transfer of 2 e- to the FAD moiety, which in
turn, passes the two electrons to the electron carrier coenzyme Q in complex II
of the electron transport system.
Reaction 6: Oxidation of succinate by succinate
dehydrogenase to form fumarate
Fumarate and malate are citrate cycle intermediates that enter and
exit the cycle from several different interconnected pathways.
Reaction 8: Oxidation of malate by malate
dehydrogenase to form oxaloacetate
Oxidation of the hydroxyl group of malate to form oxaloacetate in a
coupled redox reaction involving NAD+/NADH. The change in standard
free energy for this reaction is unfavorable
(ΔGº' = +29.7 kJ/mol), but the actual G for this reaction is favorable.
In order for this unfavorable Gº’ to allow for a favorable G, the metabolite
concentrations need to be far from equilibrium.
Based on what you know about the citrate cycle, what do you think
explains the favorable G in terms of [metabolite] in this case?
Bioenergetics of the citrate cycle
??
~2.5 ATP/NADH
~1.5 ATP/FADH2
• Citrate synthase
• Isocitrate
dehydrogenase
• α-ketoglutarate
dehydrogenase
Pyruvate
dehydrogenase is
activated by CoA-SH to
stimulate acetyl-CoA
production.
Pyruvate carboxylase
in turn, is stimulated by
acetyl-CoA to maintain
OAA for citrate
synthesis. If
carbohydrate is limiting,
(low pyruvate), then
acetyl-CoA is converted
to ketone bodies
(ketogenesis) or citrate
is shuttled to the cytosol.