Mitochondrial Bioenergetics (TCA And OxPhos) Flashcards
The TCA cycle is ___________, meaning it involves both catabolic and anabolic processes
Amphibolic
In order for the TCA and oxphos to occur, pyruvate must get into the mitochondria. How does it do this?
Mitochondrial pyruvate carrier (MPC)
What enzyme is responsible for the decarboxylation of pyruvate?
PDH (pyruvate dehydrogenase) complex
PDH is a holoenzyme composed for 3 separate enzymes, what are they?
E1 = pyruvate decarboxylase E2 = dihydrolipoyl transacetylase E3 = dihydrolipoyl dehydrogenase
Do the following act as activators or inhibitors of PDH:
Ca++
Mg++
CoA
NAD
Activators
Do the following act as activators or inhibitors of PDH:
NADH
Arsenite
Inhibitors
The overall reaction of the PDH complex is:
Pyruvate + NAD+ + ________ ——> Acetyl CoA + _______ + NADH + _______
CoA
CO2; H+
What is the purpose of pyruvate dehydrogenase phosphatase?
Activates PDH (so active form is DEphosphorylated!)
[note that PDH kinase deactivates PDH by adding a phosphate]
What would be the clinical result of patients who are PDH phosphatase deficient?
PDH would be constitutively phosphorylated, and thus inactive, meaning that glucose becomes lactate instead of acetyl CoA
The ultimate result is lactic acidosis which primarily affects the CNS
What are the 3 most regulated steps of TCA?
Acetyl CoA –> Citrate (citrate synthase)
Isocitrate –> alpha-ketoglutarate (isocitrate dehydrogenase)
Alpha-ketoglutarate –> succinyl CoA (alpha-ketoglutarate dehydrogenase)
____________ reactions act to replenish intermediates for the TCA cycle
Anaplerotic
What are the 2 major anaplerotic reactions?
Degradation of amino acids
Carboxylation of pyruvate
What classic disorder of the TCA cycle consists of global developmental delay, severe neurological problems, metabolic acidosis, severe microcephaly, and mental retardation?
2-oxoglutaric aciduria
What classic disorder of the TCA cycle consists of neurological impairment, encephalomyopathy, dystonia, increased urinary excretion of fumarate, succinate, alpha-ketoglutarate, and citrate?
Fumarase deficiency
What recently discovered disorder of the TCA cycle is associated with mutations of 2/3 subunits making up the enzyme - including SUCLA2 and SUCLG1
Succinyl CoA Synthetase Deficiency
What recently discovered disorder of the TCA cycle consists of profound hypotonia, progressive dystonia, muscular atrophy, and severe sensorineural hearing impairment?
Mitochondrial Depletion Syndrome
What is the site of most of the TCA cycle and fatty acid oxidation?
Matrix of mitochondria
All TCA enzymes are located in the mitochondrial matrix except which one?
Succinate dehydrogenase
What is the baseline pH in the mitochondrial matrix?
High (low H+ concentration)
Mitochondria continually undergo the processes of __________ and _________ to affect processes like Mt DNA stability, respiratory capacity, apoptosis, response to cellular stress, and mitophagy
Fusion
Fission
What are the 2 types of redox reactions?
The electron-only transfer (electrons are transferred between 2 metal ions - note that the oxidant is always on the side of the reaction with the electrons)
The reducing-equivalent transfer (transfer of a proton and an electron)
What does E0’ stand for?
It is the standard redox potential - which is a measure of the affinity of a redox pair of electrons. A lower E0’ = a lower affinity
Oxidative phosphorylation involves the creation of a proton gradient by pumping protons across the mitochondrial membrane, thus ____________ the pH in the intermembrane space
Decreasing (adding H+ makes it more acidic)
How does E0’ (standard redox potential) relate to dG0’?
They are inversely related
What is the chemiosmotic hypothesis?
ATP synthesis in respiring cells comes from the electrochemical gradient across the inner mitochondrial membrane by using the energy of NADH and FADH2 formed from the breaking down of energy rich molecules
What enzyme catalyzes the synthesis of ATP, and what drug is capable of inhibiting it?
ATP synthase
Can be inhibited by Oligomycin, which disrupts proton transport through the channel so the gradient cannot be created (may result in lactate accumulating in blood and urine)
What 2 factors is Oxphos most sensitive to in terms of overall regulation?
Presence of molecular oxygen
ATP/ADP ratio
What is “uncoupling” in OxPhos, and in what situations is it useful?
Electron transfer becomes uncoupled from the proton gradient, so protons re-enter the mitochondrial matrix from the intermembrane space and, instead of ATP, heat is generated
Useful for hibernating animals and newborn babies
Which of the following most accurately describes mitochondrial transport systems?
A. Symporters
B. Uniporters
C. Antiporters
D. Diporters
C. Antiporters
Antiporters are necessary in the mitochondrial membrane because reduced ______ cannot cross without them
NADH
What are the 2 shuttle systems associated with mitochondrial transport systems?
Malate-aspartate shuttle
Glycerophosphate shuttle
The malate aspartate shuttle operates in the ________, liver, and _________.
It generates NADH in the ___________, and NADH enters the ETC at complex ____
Heart; kidneys
Mt. matrix; 1
The glycerophosphate shuttle operates in the ________ and muscle.
It generates _________ in the inner mt. membrane, which then joins the ETC at ________
Brain
FADH2; CoQ
What was the first diagnosed mitochondrial disease?
Luft’s disease
What are the 2 primary causes of mitochondrial disease?
Defect in nuclear DNA encoding mitochondrial proteins
Defect in mitochondrial DNA
What are some secondary causes of mitochondrial disease?
Ischemia Reperfusion Cardiovascular disease Renal failure Drugs and aging Alcohol Smoking
