The Citric Acid Cycle: CACKreb’s Cycle

Tricarboxylic Acid Cycle: TCA

Chapter 16

The Citric Acid Cycle

– 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

Key topics: To Know

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 CycleCytosolic aconitase: 2 roles: 1. citrate isocitrate 2. iron response regulator

To become an iron response regulator, aconitase changes it shape (due to lack of iron) so it can bind RNA.

Aconitase binding iron/RNA

Isocitrate DH

Mn++ cofactor

ΔGo’ = -21 kJ/mole

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

Glycolysis

ATPase

RNA

In Animals CAC can not be used for Gluconeogensis from Ac-SCoA

E, Q, P, R

D, N, L, K, M, T, I

Porphrins: heme (cytochromes, hemoglobin), chlorophyll

In Bacteria and Plants, Not Vertebrates

Overall:

2 Ac-SCoA Succinate

Succinate OAA

Oxaloacetate CAC

NADH and FADH2

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.