Catabolism of Pyruvate Flashcards
why is it important to re-generate NAD+
- Theres only limited amounts of NAD+ present in the cell - Glycolysis reduces this into NADH + H - This needs to be re-oxidised to let glycolysis continue - Re-oxidation of NAD+ is achieved by the oxidative metabolism of Pyruvate
What is the importance of the TCA cylce
- The TCA cycle is stage 2 of glycosis
- Is it carried out in the matrix of the mitochondria
- Catabolism of pyruvate into Acytl CoA
- Generates NADH and FADH by accepting electrones
- Spinning of the TCA cycle generates electrones which are store in the form of NADH and FADH
- Therefore generates potential energy stored in the NADH and FADH which is released in the final stage and converted to the production of ATP
What is the Role of NADH
Delivers electrones to the respiratory chain
Where does the TCA cycle take place
in the Matrix of the mitochondria
What is the significance of the mitochondria in the TCA cycle
- Inner membrane: Contain
- proteins for the electrone transport chain
- ATP synthase
- Transport proteins
- Matrix contains enzyms for TCA cycle
How does Pyruvate enter the Mitochondrial matrix
- Mitochondria has 2 membranes an inner membrane and an outer membrane
- There is a PH Gradient present from the cystol to the Inner mitochondrial space - meaning the same is Acidic and postively charged with lots of H+
- This proton gradient Drives ADP and ATP exchange between inner membrane and the cystol
- Proton gradient also drives movement of Pi via a H+/Pi symport
- Proton Gradient Drives Pyruvate entery (negative molecule) via a H+/Pyruvate symport (positive charge drives entery of the negative charge by attracting it) via Facillitated diffusion
Pyruvate entry
Pyruvate (from cytosol) has to cross 2 membranes, mitochondrial space and then mitochondrial matrix – pH gradient is present from cytosol to inner membrane space (space is very acidic therefore lot of H+, positive charge), pyruvate has negative charge so movement of pyruvate across both membranes is linked to pH gradient
How is pyruvate metabolised into Acytl- CoA
- process is carried out by enzyme - Pyruvate Dehydrogenase
- Pyruvate (3C) oxidised into Acetly-CoA (2C) - CO2 produced
- NAD+ is reduced to NADH
- Irreversibel! Reaction - Acetyl CoA cannot turn back into pyruvate
- Acetyle CoA is needed for the TCA Cycle
How is the production of Acetyl CoA Regulated
- Pyruvate dehydrogenase comples is made up of 3 enzymes
- PCL is allosterically regulated by Kinases - phosphoryates them
- Phosphorylation controles the rate at which Acetyl CoA is produced
What are the 3 enzymes that regulate rate of Acetyl CoA production
- Pyruvate dehydrogenase
- Dihydrolipoyl transacetlyase
- Dihydrolipoyl dehydrogenase
What is the Mechanism of the TCA cycle
- 8 reations in total
- Acetyle-CoA - 2 carbon molecules enters the TCA cycle
- Oxaloacetate 4C joins with the acetyle CoA to produce a 6c molecules Citrate
- This 6C molecule is Decarboxylated twice -
- 1 Co2 produced
- four oxidation reations take place (carbons lost)
- Yields 3 NAHD + H+ and 1 FADH2
- one GTP is formed
- The 4C molecule is re-created and cycle goes on
all enzymes of the TCA cycle are located in mitochondiral matrix apart from which one?
Succinate dehydrogenase
- Located in Inner membrane of mitochondria
Whats the reaction of Succinate dehydrogenase
Succinate + FAD —> Fumarate + FADH2
What are the main features of the TCA cycle
- All products of the CTA cylce can give rise to Acetyl coA
- These can be oxidised completly to Co2 via the TCA cycle
- All ezmyes are found in matrix exception - Succinate dehydrogenase (inner membrane)
- Each TCA cycle takes one Acetyl CoA to produce 2 CO2
- Each turn = 3 NADH2 + 1 FADH2
- one Substrate level phosphorylation = 1 GTP production
How is the TCA cycle controlled
- Inhibition = High ATP, Acetyl CoA and NADH
- Stimulation = ADP, NAD+
- Enzyme inhibition = Succinyl-CoA, Acetyl CoA means plenty of precursor molecules for biosynthetic reactions = regulates flux through pathway
What is pyruvate Dehydrogenase complex Deficiency?
- Sex linked disease = Carried on the X chromosome
- Male carriers = Lethal still born
- Female Carries = Survivable Adolescent onset with variable symptoms severity
What does brain pathology look like with PDCD
- Brain lesions
- Defective symmetry left and right hemispheres
- large cyst formation
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