Mitochondrial synthesis of ATP: Kreb's cycle and oxidative phosphorylation. Flashcards
(34 cards)
What is the concentration of ATP in most cells?
6mM
How much ATP does the average human body contain?
75g
What is the average turnover of ATP per day?
75kg
What proportion of the energy in food is converted to ATP and what proportion of that is converted to useful work?
50% and 50%
Where is most of the body’s ATP synthesised?
Mitochondria
What occurs in the mitochondrial matrix space?
Contains wide range of enzymes. Krebs cycle, fatty acid oxidation, urea cycle (in liver). High concentrations of substrates cofactors and ions. Contains mitobhondrial DNA, RNA and ribosomes.
What is present in the mitochondrial intermembrane space?
Has metabolite and ion concentrations similar to cytosol. Contains cytochrome c.
What is the link reaction?
Pyruvate -> acetyl CoA
Pyruvate transported across the inner membrane from cytosol to matrix and reaction catalysed by pyruvate dehydrogenase.
Which vitamin is essential for the function of pyruvate dehydrogenase?
Thaimine (vit B1)
What conditions are caused by lack of thiamine?
Beriberi - neuro/cardio symptoms
Wernicke-Korsakoff syndrome - in alcohol abuse.
Why is pyruvate dehydrogenase a key decision point in metabolism?
Acetyl CoA cannot be converted back to glucose in humans. Conversion of pyruvate to acetyl CoA commits the C atoms of glucose to energy production or lipid synthesis.
What inhibits pyruvate dehydrogenase?
High energy levels
What are the two stages of the Kreb’s cycle?
- Synthesis of 6-C compound (citrate) which then looses 2C as 2xCO2 to become a 4-C compound (succinyl CoA).
- Oxidation of 4-C compound to regenerate oxaloacetate and initiate another round of the cycle.
What are the main outputs of the Kreb’s cycle?
Reduced coenzymes NADH and FADH2 as electron carriers.
CO2 - waste product.
1 GTP (=1 ATP)
What are the control points in the citric acid cycle?
Pyruvate -> acetyl CoA - inhibited by ATP, acetyl CoA and NADH
Acetyl CoA -> citrate - inhibited by ATP, NADH, succinyl CoA and citrate
Isocitrate -> alpha-ketoglutarate - inhibited by ATP, NADH. Stimulated by ADP and NAD+
Alpha-ketoglutarate -> succinyl-CoA - inhibited by ATP, NADH, and succinyl-CoA.
What are key enzymes in the Kreb’s cycle?
Citrate synthase, isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase.
Why do patients with type I diabetes synthesise ketone bodies?
Cannot use glucose effectively in the absence of insulin.
Gylcolysis inhibited and pyruvate low.
Gluconeogenesis is not inhibited - oxaloacetate and malate removed to form glucose.
In the absence of insulin fatty acids are used to supply acetyl CoA. Acetyl CoA levels high.
Lack of oxaloacetate prevents acetyl CoA from entering Kreb’s cycle so ketones synthesised instead.
What is the last ATP synthesis step?
Oxidative phosphorylation.
What are the two tightly coupled processed that make up oxidative phosphorylation?
Electron transport and ATP synthesis.
What is electron transport?
The energy (reduction potential) of the electrons in NADH/FADH2 is used to create a proton gradient across the inner mitochondrial membrane - OXIDATION.
How does ATP sysnthesis occur after oxidative phosphorylation?
Energy from the proton gradient is used to phosphorylate ADP to synthesise ATP - PHOSPHORYLATION.
What are the membrane-bound components of the electron transport chain?
Complexes I-IV
How does the electron transport chain work?
Electrons are transferred from one electron carrier to another.
Complex I - NADH -> NAD+
Complex II - FADH2 -FAD
Yields 2 electrons, both pass through complex 3, ubiquinone and cytochrome c
At complex IV they are donated to oxygen reducing it to water.
Energy is released from each step.
Which step in the electron transport chain is blocked by cyanide?
O2 + 2H -> H2O at complex IV
