Flashcards in Lecture 10: Mitochondrial Bioenergetics Deck (65):
________ is the activated form of acetate
Where is he high energy bond in acetyl CoA located?
What is the deltaG of acetyl coA?
How does pyruvate enter the mitochondria?
Mitochondrial pyruvate carrier (MPC)
________ catalyzes the deccarboxylation of pyruvate once pyruvate enters the mitochondria
Pyruvate dehydrogenase complex (PDC)
In a phosphatase deficiency, PDC is always in the inactive form. Is this phosphorylated or dephosphorylated?
What are the symptoms of a phosphatase (affecting PDC) deficiency?
Glucose is converted to lactate rather than acetyl CoA, resulting in constant lactic actidosis
- The CNS is the most effected
In patients with a PDC deficiency, it is important to limit ____ in their diet to prevent further buildup of lactic acid
Alanine because Ala is converted to pyruvate via a transamination reaction hen pyruvate cant be processed so its converted to lactate causing further buildup
In a high energy charge, what inhibits PDH?
In a low energy charge, what stimulates PDH?
What 3 steps of TCA are regulated?
OAA -> Citrate (citrate synthase)
Isocitrate -> Alpha-ketoglutarate (Isocitrate dehydrogenase)
Alpha-ketoglutarate -> Succinyl CoA (alpha-ketoglutarate dehydrogenase)
What is the rate limiting step of TCA?
Isocitrate -> alpha-ketoglutarate (isocitrate dehydrogenase)
Where in TCA is there substrate level phosphorylation for a high energy bond?
Succinyl CoA -> Succinate (Succinate thiokinase)
- Creates GTP
How many moles of ATP is generated from 1 mole of glucose oxidized via TCA cycle?
20 -> 10moles of ATP/1 pyruvate X 2 pyruvate/1 mole of glucose = 20
What are the two major anaplerotic reactions that provide intermediates to replenish the TCA cycle?
1) Degradation of amino acids
2) Carboxylation of pyruvate (pyruvate -> OAA -> gluconeogenesis)
What amino acids can be converted into OAA?
Asn -> Asp -> OAA
What amino acids can be converted into fumarate?
Phe, Tyr, Asp
What amino acids can be converted into succinyl CoA?
Thr, Met, Ile, Val -> Propionyl CoA -> Succinyl CoA
What amino acids can be converted into alpha ketoglutarate?
Gln, Pro, His, Arg -> Glutamate -> Alpha-ketoglutarate
Alpha ketoglutarate can form what amino acids?
Alpha ketoglutarate -> Glutamate -> Gln, Pro, Arg
What is 2-Oxoglutaric aciduria?
A rare disorder with global developmental delay and sever3e neurological problems in infants
- Metabolic acidosis, severe microcephaly, mental retardation
What is Fumarase deficiency?
Characterized by severe neurological impairment. Fatal outcome within first 2 years of life.
- Encephalomyopathy, dystonia, increased urinary excretion of fumarate, succunate, alpha-ketoglutarate, and citrate (can find all in urinalysis
What is succinyl CoA synthetase (SCS) deficiency?
Associated with mutations two out of three subunits making up the enzyme -> SUCLA2 and SUCLG1
- These genes encode the beta subunit of the ADP-forming SCS and alpha-ketoglutarate subunit of SCS
What symptoms is mitochondrial depletion syndrome associated with?
Profound hypotonia, progressive dystonia, muscular atrophy, and severe sensory neural hearing impairment
Where does oxidative phosphorylation occur?
Inner mitochondrial membrane
Where does TCA and FA oxidation occur?
What is an electron only transfer?
Electrons are transferred between two metal ions
**The oxidant is always on the side of the reaction with the electrons**
What is a reducing-equivalent transfer?
Involves transfer of a proton and an electron
__________________ is a measure of the affinity of a redox pair of electrons and uses volt (V) as the unit
Standard redox potential
Does a redox pair with a lower standard redox potential have a higher or lower affinity for electrons?
Lower -> hence gives them u easily to a redox pair with a higher standard redox potential
What is the relationship between Gibbs free energy and standard redox potential?
They are inversely related
Electrons flow from the molecules with ______ standard redox potential to that with _______ standard redox potential
O2 from ETC complex 1 and 3 becomes a superoxide anion. What enzyme is used to convert a superoxide anion to hydrogen peroxide and what is its cofactor?
SOD; cofactor = Mn or Mg
Once a superoxide anion is converted to hydrogen peroxide, it can be made into either water or GSSG. What enzyme is used to convert it to water?
Once a superoxide anion is converted to hydrogen peroxide, it can be made into either water or GSSG. What enzyme is used to convert it to GSSG?
GSSG reductase or thioreoxin reductase can then convert that to GSH which is a hydroxyl radical
When there is an overproduction of RNS and ROS, what 3 things are damages induced on?
What are the 3 key goals of OxPhos?
1) To transfer electrons from NADH and FADH2 to O2
2) To establish a proton gradient across the inner mito membrane
3) To synthesize ATP
Electron transfer through the respiratory chain lead to the pumping of H+ from __________ to ________
Matrix -> inner mito space
What are the 2 factors that constitute a proton motive force (pmf) to drive ATP synthase?
1) pH gradient
2) Membrane potential
What is the necessary power needed by ATP synthase to form ATP?
What are the inhibitors of ATP synthase (complex 5)
What is the role of oligomycin
Inhibits ATP synthase by disrupting proton transport through the channel
CoQ (ubiquinone) is a lipophilic molecule that is not a prosthetic group for which complex?
What cofactors are in complex I of ETC?
FMN and Fe-S
What cofactors are in complex II of ETC?
What cofactors are in complex III of ETC?
What cofactors are in complex IV of ETC?
What inhibits complex I of ETC?
What inhibits complex 2 of ETC?
What inhibits complex III of ETC?
What inhibits complex IV of ETC?
How do uncoupling proteins work?
P-ADP uncoupled from the electron transfer, protons reenter he mito matrix from the intermembrane space, TCA cycle and electron transfer to O2 are accelerated, ATP synthase is inhibited and HEAT is generated
Explain the malate-aspartate shuttle
Used to shuttle NADH into the mitochondria
OAA + NADH -> Malate -> Malate into mito matrix -> release of NADH in matrix -> OAA formed -> alpha-ketoglutarate and aspartate -> alpha-ketoglutarate leaves mito and goes to cytosol where the cycle is repeated
Explain the glycerophosphate shuttle
Used to get NADH into the mitochondria
DHAP -> Glycerol-3-P -> Intermembrane space of mito -> DHAP with transfer of FADH2 and DHAP goes back to cytosol to repeat the process
Where does the malate-aspartate shuttle operate?
Heart, liver, kidney
Wha does the malate-aspartate shuttle generate?
NADH in mito matrix
Where does the glycerophosphate shuttle operate?
In skeletal muscle and the brain
What does the glycerophosphate shuttle generate?
FADHs in the inner mito membrane
- Joins ETC at CoQ
What was the first diagnosed mitochondrial disease?
What are the 2 primary causes of mitochondrial diseases?
Defect in nuclear DNA (nDNA) encoding the mito proteins
Defect in mitochondrial DNA (mDNA)
What are some secondary causes of mitochondrial diseases?
Ischemia, reperfusion, cardiovascular diseases, renal failure, alcohol, smoking, drugs, aging
What are the metabolic features of mitochondrial diseases?
Low energy production
Increased free radical production
What type of inhibitor does CO act as in the ETC?
Competitive (raises Km)
What type of inhibitor does CN and H2S act as in ETC?
Noncompetitive (decreases Vmax)