Flashcards in Mitochondrial Bioenergetics-Fixed Deck (51):
The TCA cycle is amphibolic. What does that mean?
Catabolism and anabolism
Where does the TCA cycle take place?
Inside the mitochondria
How does the TCA cycle work like a roundabout?
Facilitate traffic flow (precursors for biosynthesis)
What enters TCA?
Acetyl CoA is the activated form of _____
What are the chemical reaction types of the arows? Glucose-----> 2 Pyruvate ----> 2 Acetyl CoA
What enzyme brings Pyruvate into the mitochondria?
Mitochondrial Pyruvate Carrier
What enzyme decarboxylates Pyruvate into Acetyl CoA?
Pyruvate Decarboxylase Complex (PDC)
Is the Pyruvate Decarboxylase Complex (PDC) activated or inactivated in phosphorylated form?
PDC is inactive in phosphorylated form
In a phosphatase deficiency:Is PDC phosphorylated?Is it active or inactive?Glucose is converted to ______ instead of Acetyl CoaThe disease it results in is called ____ _____
Yes always phosphorylated
Lactic Acidosis (some lactate decarboxylates into ethanol)
In a high energy state, what inhibit the Pyruvate Dehydrogenase complex?
ATP, NADH, Acetyl CoA
In a low energy state, what activates the Pyruvate Dehydrogenase complex?
What is the rate limiting step in the TCA cycle? (the enzyme)
What are the three regulated TCA cycle steps? (the enzyme)
What are the energy products of 1 cycle of the TCA cycle (1 pyruvate)?
1 GTP1 FADH23 NADH(also 2 Co2)
What is the molecule order of the TCA cycle?
Oxaloacetate + Acetyl CoACitrateIsocitratea-ketoglutarateSuccinyl-CoASuccinateFumarateMalateOxaloacetate
When cellular ATP levels are low, TCA cycle activity is _____. When cellular ATP levels are high, TCA cycle is ______
What do Anaplerotic reactions do for the TCA cycle?What are the two major Anaplerotic reactions?
They provide intermediates to replenishDegradation of Amino AcidsCarboxylation of Pyruvate
What Amino acids enter the TCA cycle at Fumarate? (3)
Phenylalanine, Tyrosine, Aspartate
What Amino Acids enter the TCA cycle at alpha-keto glutarate? (5)
Glutamine, Proline, Histidine, Arginine are all converted to Glutamate then TCA
What amino acids enter the TCA cycle at Oxaloacetate? (2)
What amino acids enter the TCA cycle at Succinyl CoA and at what intermediate?
Threonine, Methionine, Isoleucine, Valine all enter through propionyl CoA
How is the TCA cycle linked to glucose synthesis?
Malate converts to oxaloacetate, then Phosphoenolpyruvate, then glucose.
How is the TCA cycle linked to Lipid synthesis?
Citrate to Acetyl CoA, then Fatty acids/isoprenoids
What two TCA cycle substrates are linked to AA synthesis and which AAs can they produce?
Oxaloacetate: Aspartate and Asparagine
a-Ketoglutarate: Glutamate, then Glutamine, proline, and arginine
Tca substrate Succinyl CoA can be used as a subsrate for what molecule?
Porphyrins ----> Heme
What is 2-Oxoglutaric aciduria?
TCA cycle disorder, metabolic acidosis, developmental decay/neurological problems in infants.
What is Fumarase deficiency?
TCA cycle disorder, severe neurological impairment/fatal outcome in first 2 years. Urine Fumarate released along with others. Encephalomyopathy.
What is Succinyl-CoA synthetase deficiency?
TCA cycle disorder, mutations on two of the three subunits making up the enzyme (SUCLA 2 AND SUCLA 1)
What is Mitochondrial depletion syndrome?
TCA cycle disorder, hypotonia, dystonia, muscular atrophy, sensory neural and hearing impairment.
Where does Ox-phos occur in mitochondria? What about TCA cycle and Beta Oxidation?
What is a reductant?
Same as a reducing agent, it is the thing helping the other get reduced.
What is the electron-only transfer?
Electrons transfered between two metal ions
What is the reducing equivalent transfer?
Transfer of a proton and an electron.
True false: A redox pair with a lower Eo will give up their electrons to a pair with a higher Eo?
Yes, because Eo (the standard redox potential) is a measure of the affinity of a redox pair of electrons.
How are ΔE and ΔG related?
They are inversely related. ΔG=-nFΔE. The higher the E, the more affinity it has for electrons.
Three key goals of Ox-Phos?
Transfer electrons from NADH/FADH2 to O2
Proton gradient across inner membrane
What two factors constitute a proton motive force by Complex V? What is the name of this hypothesis?
What is an inhibitor of Complex 5 ATP Synthase? (AKA an uncoupler cause it uncouples electron transfer/proton gradient from ATP synthesis)
What is the respiratory chain enzyme complex order pathway?
C1 and C2 ---> CoQ (Ubuiquinone) ---> C3 ---> Cytochrome C ---> C4 ---> O2
Which respiratory complex accepts NADH?
Which respiratory complex accepts FADH2?
Which respiratory complexes pump protons into intermembrane space? Which comlex uses them for energy?
1, 3, 4
5 (ATP Synthase)
What happens when electron transfer in respiration chain is inhibited?
Decrease in proton pumping, decrease in proton gradient, inhibition of ATP synthesis
What is Oxphos pathway sensitive to? (2)
O2, ATP/ADP ratio
If the proton gradient is disrupted and H+ seeps back into mitochondrial matrix, what occurs? (3)
TCA Cycle/electron transfer to O2 accelerated
ATP synthase inhibited
What are the two shuttle systems to get reduced NADH into mitochondrial membrane?
How does the malate-aspartate shuttle work? Where is it located?
Reduced NADH uses malate to shuttle in its electrons, malate converted to NADH, then the malate is converted to aspartate and returns to cytosol.
Liver, kidneys, heart
How does the Glycerophosphate shuttle work?
Where is it located?
Reduced NADH gives its electrons to Glycerol 3-P, which is used to generate FADH2 in inner mitochondrial matrix.
Muscle and brain
What are the primary causes of mitochondrial diseases?
What are some Metabolic features? Clinical features?
Defect in nuclear DNA encoding Mitochondrial proteins
Defect in Mitochondrial DNA
Metabolic features: Low energy, increased free radicals, lactic acidosis
Clinical features: muscle weakeness, cardiomyopathy, seizures.