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
