L16 Krebs Cycle

Introduction to the Krebs Cycle
- Focus on finishing previous discussions and moving into oxidative phosphorylation.
- Overview of glucose oxidation to ATP production and electron transfer to oxygen.

The cycle begins with the combination of oxaloacetate and acetyl CoA, forming citrate.
Inputs:
- 2 carbon atoms from acetyl CoA.
- 1 CoA is released during the process.
Outputs:
- Carbons (as CO2) removed along the way.
- 8 electrons per cycle that must be transferred to oxidative phosphorylation for ATP production.

Key focus areas on changing oxidation states within the Krebs cycle:
- Bottom left carbon going from CH2 to COO in citrate oxidation.
- Top left undergoing a change from CH2 to a carbonyl carbon in a later step.
First half of the cycle involves significant oxidation of carbons and decarboxylation events leading to electron harvest.

First Step: Arrangement of hydroxyl groups leads to internal redox changes.
- Shift of hydroxyl from a middle carbon to the bottom left carbon begins oxidation.
Oxidation of bottom left carbon occurs first, involving a transition from alcohol to carbonyl state.
Decarboxylation Events:
- Carbons are lost in the form of CO2, leading to electron release (3 electrons total for bottom left carbon).
- Formation of enolate intermediate stabilized through adjacent carbonyl groups.

Importance of reduction potentials in determining energetics within the Krebs cycle.
Some steps exhibit near-zero Delta E in biological contexts, indicating reversibility and lack of energy capture.
Delta E values inform the driving force and potential energy storage throughout the pathway.

Citrate Synthase: Main enzyme facilitating the formation of citrate from oxaloacetate and acetyl CoA.
Isocitrate Dehydrogenase: Enzyme that takes isocitrate through oxidation and decarboxylation.
Naming patterns in enzymology (dehydrogenase indicating redox reactions).

Main pathway for electrons transferred from NADH to molecular oxygen via a series of complexes (Complexes I, III, and IV).
Each complex catalyzes redox reactions, moving electrons through a chain until they reach oxygen.
- Complex I: oxidizes NADH to Q (coenzyme Q).
- Complex II: succinate dehydrogenase spots electrons from FADH2 into Q (not a part of the NADH route).
- Complex III: transfers from QH2 to cytochrome c.
- Complex IV: final reduction of electrons to oxygen.

Protons (H+) are pumped across the inner mitochondrial membrane during electron transfer, creating a proton gradient essential for ATP synthesis.
Energy from the redox reactions is harnessed to establish this gradient, which can later be used in ATP synthase for ATP production.

Mitochondria are unique organelles featuring their own DNA and ribosomes; believed to be endosymbiotic bacteria.
Site of Krebs cycle and electron transport linked to cellular respiration.
Matrix: Innermost compartment and site of Krebs cycle.
Intermembrane Space: Holds higher proton concentration, creating a potential difference.

Each turn of the cycle extracts electrons, producing NADH and GTP, with carbon atoms released as CO2. Each half of glucose from glycolysis holds 12 electrons, which are systematically reduced and transferred throughout both the Krebs cycle and the electron transport chain to ultimately generate ATP.