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The Citric Acid Cycle
The Citric Acid Cycle
Joe Maleszewski
March 25, 2003
Lecture Outline
• What is metabolism?
• Review of Glycolysis
• Assault on Pyruvate
• Overview of Kreb’s Cycle (TCA)
• Reactions of Kreb’s Cycle
• Regulation of Kreb’s Cycle
• Where are we going next?
Metabolism
• Metabolism is the sum of
all chemical reactions
within a cell (or whole
organism), including
energy-releasing
breakdown of molecules
and the synthesis of
complex molecules
• It is extraordinarily
COMPLEX
Metabolism
• The reactions of metabolism are
MANY
• In this class we will discuss
some of the major reactions:
– Glyco - Lysis (glycolysis)
– The Citric Acid Cycle
– The Electron Transport Chain
• It is important to become
familiar with some of the key
players in these reactions
– ATP
– NAD/NADH
– The various other intermediate
compounds (many are sugars)
Adenosine Triphosphate (ATP)
Reduction
Oxidation
Reduction
Oxidation
ATP X 2 ATP X 4
ADP X 4 NADH X 2
NAD X 2 ADP X 2
Review of Glycolysis
The Fate of Pyruvate
• In the ABSENCE of
oxygen - pyruvate gets
fermented to oxidize
NADH to NAD so that
glycolysis (ATP
production can
continue.
The Fate of Pyruvate
• In the PRESENCE of
oxygen - Pyruvate gets
turned into Acetyl
CoA and then added to
other molecules in
order to liberate CO2
(the Calvin Cycle -
backwards).
The Assault on Pyruvate
• Pyruvate moves easily
passed the porous
outer mitochondrial
membrane and is then
transported through
the inner membrane
where it encouters…
The Pyruvate Dehydrogenase
Multienzyme Complex
The Assault on Pyruvate
• The Pyruvate
Dehydrogenase
multienzyme complex
will “assimilate”
Pyruvate into Acetyl
CoA by “ripping off”
Pyruvate’s CO2 “head”
and attaching chemical
parts to it’s “neck.”
The Assault on Pyruvate
The Assault on Pyruvate
Acetyl CoA moves on to the
Kreb Cycle
(The Citric Acid Cycle)
Regulation of Kreb’s Cycle
• The regulation is mediated
via allosteric inhibition by
products on enzymes used
previously in the cycle.
• For example, an increase in
Citrate will cause a
decreased activity of
Citrate Synthase
• An increased NADH or
Acetyl CoA will decrease
Pyruvate Dehydrogenase
activity
Where have we been?
Kreb’s Cycle Summary
• Remember, we get 3-
NADH from TCA along
with the one we got from
the Pyruvate DH reaction
and then an FADH2 (a lot
like NADH, but less
reducing power) and an
ATP and this is just from
ONE Pyruvate molecule
(remember: 2 Pyruvates
per Glucose molecule)
Where are we going?