Download Citric Acid Cycle

Chapter 16
The Citric Acid Cycle: CAC
Kreb’s Cycle
Tricarboxylic Acid Cycle: TCA
The Citric Acid Cycle
Key topics: To Know
– Also called Tricarboxylic Acid Cycle (TCA) or
Krebs Cycle. Three names for the same thing.
– Cellular respiration and intermediates for
biosynthesis.
– Conversion of pyruvate to activated acetate
– Reactions of the citric acid cycle
– Anaplerotic reactions to regenerate the acceptor
– Regulation of the citric acid cycle
– Conversion of acetate to carbohydrate precursors
in the glyoxylate cycle
Discovered CAC in Pigeon Flight Muscle
Cellular Respiration
• Process in which cells consume O2 and produce CO2
• Provides more energy (ATP) from glucose than Glycolysis
• Also captures energy stored in lipids and amino acids
• Evolutionary origin: developed about 2.5 billion years ago
• Used by animals, plants, and many microorganisms
• Occurs in three major stages:
- acetyl CoA production (This chapter)
- acetyl CoA oxidation (This chapter)
- electron transfer and oxidative phosphorylation
(Chapter 19)
Overall Picture
Overall Picture
The area blocked off all
takes place in the
Mitochondrion. So, first
pyruvate has to get
transported from the
cytoplasm into the
mitochondrion.
In this Figure, only
Glycolysis is in the
Cytoplasm.
Acetyl-CoA production
occurs in the
mitochondria.
Acetyl-CoA enters the
CAC.
Pyr DH is a Complex Enzyme
Pyruvate Dehydrogenase
Model
TEM
Lipoic Acid is linked to a Lys (K)
Remember HSCoA ? from Chapter 1
It is down here
One Unit of Pyr DH
EOC Problem 6: Tests your knowledge of PyrDH.
EOC Problem 7: Thiamin deficiency and blood pyruvate.
Pyr DH is a Cool Enzyme
EOC Problem 5: NAD+ in oxidation and reduction
reactions (a through f should be easy).
Citrate Synthase
Convention to write
incoming Acetyl on
Top
EOC Problem 32, further on the
thermodynamics of Citrate
Synthase.
Aconitase, the Ferris Wheel
The Aconitase Iron Sulfur Complex
Aconitase has More than One Role
Mitochondrial aconitase: Citric Acid Cycle
Cytosolic aconitase: 2 roles:
1. citrate  isocitrate
2. iron response regulator
Aconitase binding iron/RNA
To become an iron
response regulator,
aconitase changes it
shape (due to lack of iron)
so it can bind RNA.
Isocitrate DH
ΔGo’ = -21 kJ/mole
Mn++ cofactor
EOC Problem 8 is all about IsocitDH.
αKG DH is Just Like Pyr DH
TPP,
lipoate
FAD
Succinyl CoA Synthetase : Substrate Level Phosphorylation
One GTP = One ATP
Nucleoside diphosphate kinase:
GTP + ADP  GDP + ATP
ΔGo’ = 0
Succinate DH = Old Yellow
Malonate was One of the First Competitive
Inhibitors Known
Fumarase: the addition of water in two parts
Don’t Confuse Malate and Maleate
Malate DH is Endothermic
CAC Energetics
Watch Where the Label Goes
EOC Problem 18: Labeled glucose carbons
and where they go in CAC.
Citrate is Prochiral
The Acetyl Portion does not get oxidized to CO2
Until the Second Round
And it gets randomized at Succinate
Energetics of Glycolysis and CAC in ATPs
EOC Problems 1 and 2: Balanced equations for Glycolysis
and CAC.
CAC in Anaerobic Not-Respiratory Organisms
It’s a 2 input
FORK
This is Why
OAA  D, N, I, K,
T, M
Anaplerotic Reactions
Regulation of CAC
EOC Problem 30 and 31 on
oxygen and NAD regulation
of CAC.
Pathway Proteins Form Functional Units but
It’s Concentration Dependent
Pathways are Protein Modules
Flagella
LPS
Outer Membrane
Peptidoglycan
Cytoplasmic
Membrane
ATPase
Glycolysis
RNA
In Animals CAC can not be used for
Gluconeogensis from Ac-SCoA
D, N, L, K,
M, T, I
Porphrins:
heme
(cytochromes,
hemoglobin),
chlorophyll
E, Q, P, R
In Bacteria and Plants, Not Vertebrates
Overall:
2 Ac-SCoA  Succinate
Succinate  OAA
NADH and FADH2
Oxaloacetate
CAC
Glyoxylate Cycle in Plants in a Membrane Body
Linkage to
Gluconeogenesis
in Plants
Regulation
Linkage
Things to Know and Do Before Class
1. Pyruvate DH…all three parts and cofactors.
2. Chemistry of each step in Citric Acid Cycle.
3. Overall CAC thermodynamics (which steps are at Eq and
which are drivers.
4. Prochiral nature of citrate.
5. Amphibolic nature of CAC and why fermenters need
almost all of CAC.
6. Importance of anaplerotic reactions and how they work.
7. Glyoxylate Cycle (mammals lack) but plants, some
invertebrates and bacteria have it. What does it do?
8. EOC Problems 1-9, 16, 18, 19, 30-32.