TCA/Krebs/Citric Acid Cycle Stage 1 Flashcards
Cellular Respiration
Process in which cellular energy is generated through the oxidation of nutrient molecules with O2 as the ultimate electron acceptor.
What is the 3 stage process of cellular respiration
- Carbons (can be pyruvate or fatty acids) from metabolic fuels are incorporated into acetyl-CoA (2-carbon molecules)
- The citric acid cycle oxidizes acetyl-CoA to produce CO2, reduced electron carriers (NADH, FADH2), and a small amount of ATP.
- The reduced electron carriers (NADH, FADH2) are reoxidized, providing energy for the synthesis of additional ATP.
Pyruvate oxidation and the citric acid cycle occur in
the matrix of the mitochondria
The oxidative phosphorylation is performed by enzymes located on
the inner membrane of the mitochondria.
T or F: 90% of the energy produced by a cell comes from the citric acid cycle and oxidative phosphorylation
True
T or F: Membrane strucutree of mitochondria is not folded and increases surface area
False, it is folded to increase surface area
Acetyl-CoA originates from 3 pathways:
- Carbohydrates: pyruvate from glycolysis is transformed into acetyl-CoA by pyruvate dehydrogenase
- Lipids: β-oxidation of fatty acids produces acetyl-CoA (Lecture 9 (Fatty acid catabolism)
- Proteins: amino acid catabolism produces either pyruvate which can be converted to acetyl-CoA or acetyl-CoA directly (Lecture 14 (Amino acids deamination)
Where does acetyl-CoA attach onto Coenzyme A
The acetyl-CoA attaches to the thiol group because it is highly exergonic through a hydrolysis reaction
To generate acetyl CoA, pyruvate needs
to enter the mitochondrial matrix via MPC
Pyruvate once in the mitochondrial matrix is converted to
acetyl-CoA by pyruvate dehydrogenase (PDH)
2 characteristics of converting pyruvate to Acetyl-CoA
- Oxidative decarboxylation
- Irreversible
Where is the electron stored on NAD+
The blue part
Reduction of NAD+ to NADH
3 characteristics of the pyruvate dehydrogenase complex
- Multienzyme complex
- 3 enzymes and 5 cofactors
- This complex organization allows the channeling (Product enters one part and exists out of the channel through another part) of substrates.
What are the 3 enzymes and their matching cofactors of the pyruvate dehydrogenase complex
5 steps to acetyl-CoA formation
Function of the lipoyl domain
Carries the substrate and is where the reaction occurs (LD in image)
Step 1 of Acetyl-CoA formation
-Carbon-1 (C1) of pyruvate is released Forming CO2
-A bond is formed between C-2 and TPP
Step 2 of Acetyl-CoA formation
- The hydroxyethyl group is transferred to the lipoic acid portion of the lipoyl domain (LD).
- Lipoic acid is covalently attached to a lysine on the LD of E2
- Two electrons are also transferred during this reaction.
Step 3 of Acetyl-CoA formation
- Transesterification resulting in the production of an acetyl-CoA.
- Reduction of the LD.
Step 4 Acetyl-CoA formation
- LD is reoxidized.
- Electrons are transferred to an E3 Cys-Cys disulphide bond.
Step 5a Acetyl CoA Formation
- 5a: E3 catalyzes oxidation of the cysteines by the transfer of electrons to FAD to generate FADH2.
- Flavin nucleotides (FAD and FMN) are tightly bound to flavoproteins (i.e. E3) so They act as cofactors
EXAM QUESTION: Flavin nucleotides (FAD and FMN) are tightly bound to flavoproteins (enzyme) so they cannot diffuse (storage happens locally) so always. Stays with the enzyme
T or F: Flavin nucleotides (FAD and FMN) are tightly bound to flavoproteins (enzyme) so they cannot diffuse (storage happens locally) so always. Stays with the enzyme
True
T or F: Flavin nucleotides (FAD and FMN) are tightly bound to flavoproteins (enzyme) so they cannot diffuse (storage happens locally) so always. Stays with the enzyme
True
Step 5b Acetyl-CoA Formation
- 5b: E3 catalyzes the reduction of NAD+ to form NADH + H+ by transferring the electrons stored on FADH2 to NAD+.
- NADH isn’t bound to E3
- Can diffuse to reoxidation centers.
- Now the cycle is back where it started and can restart
Why do we need all these steps and transfer of electrons in the formation of Acetyl-CoA
They do all these steps based on transfer potential of electrons (rather than just jumping directly to the substrate it needs)
2 types of covalent modification of E1 to control pyruvate dehyrogenase complex
- Inhibited by PDH kinase phosphorylation
- Activated by PDH phosphatase dephosphorylation
What are the effects of ADP, ATP, NADH, and Acetyl-CoA on pyruvate dehydrogenase complex
- When ATP, NADH and acetyl-CoA are in abundance, they activate PDH kinase, which phosphorylates PDH and inactivates it.
- PDH kinase is inhibited by pyruvate and ADP which dephosphorylates PDH and activates it
What are the effects of Ca2+ and Mg2+ on pyruvate dehydrogenase complex
- When Ca2+ et Mg2+ are in abundance, they activate PDH phosphatase, which dephosphorylates PDH and activates it.
- Ca2+ is a critical signaling molecule for muscle contraction and in response to epinephrine.
- When you have high concentration of mg2+ = means we have less ATP because Mg2+ binds to ATP
In adipose tissue (also in the liver) PDH phosphatases is regulated by
insulin, thereby activating PDH:
- Insulin is released in response to high blood glucose levels.
- It stimulates glycolysis (pyruvate), glycogenesis (glycogen) and lipogenesis (fatty acids). = after a meal
- Acetyl-CoA is the precursor of fatty acid synthesis, PDH activation will allow the synthesis of fatty acids from glucose in adipocytes and hepatocytes.
