Chapter 16
The Citric Acid Cycle: CAC Krebs 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
Go = -21 kJ/mole Mn++ cofactor EOC Problem 8 is all about IsocitDH.
KG DH is Just Like Pyr DH
TPP, lipoate FAD
Succinyl CoA Synthetase : Substrate Level Phosphorylation
One GTP = One ATP
Nucleoside diphosphate kinase:
G o = 0
GTP + ADP GDP + ATP
Succinate DH = Old Yellow
Malonate was One of the First Competitive Inhibitors Known
Fumarase: the addition of water in two parts
Dont 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
Its 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 Its Concentration Dependent
Pathways are Protein Modules
Flagella LPS Outer Membrane Peptidoglycan
Cytoplasmic Membrane
Glycolysis
ATPase
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 DHall 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.
