Flashcards in Mitochondrial Energetics Deck (18):
Where does the TCA cycle take place?
Inside the mitochondrial matrix
What are the energy equivalent substances created in TCA?
3 NADH, 1 FADH2 and 1 GTP
1 mol NADH = 2.5 mol ATP
1 mol FADH2 = 1.5 mol ATP
1 mol GTP = 1 mol ATP
What three nutrients can Acetyl CoA come from?
carbohydrates via glycolysis (pyruvate) >> decarboxylation into acetyl CoA
Lipids: fatty acids go through beta oxidation to form acetyl CoA
proteins: at extreme levels of starvation acetyl CoA can be produced by breaking down various amino acids
What does PDC (pyruvate dehydrogenase complex) do
PDC/PDH is the enzyme complex that catalyzes the decarboxylation of pyruvate inside the mitochondrial matrix into acetyl CoA. In doing so releasing NADH and CO2. There are three enzymes (E1, E2, E3) in the complex. Pyruvate dehydrogenase phosphatase (PDP) and pyruvate dehydrogenase kinase (PDK) are tightly bound to the PDC.
PDC and phosphatase deficiency
When PDC is phosphorylated it is INACTIVE. Therefore, if someone has a phosphatase deficiency the PDC will remain inactive and not convert pyruvate into acetyl CoA, rather pyruvate will be converted solely into lactic acid causing lactic acidosis (effects CNS).
How is PDC/PDH regulated?
PDP activates PDC via dephosphorylation
PDK (kinase) inactivates PDC via phosphorylation
PDC is activated with PDP is activated/PDK inhibited
PDC is inactivated when PDP is inhibited/PDK is activated.
OVERALL: PDC WILL ONLY CONVERT PYRUVATE INTO ACETYL COA WHEN PDC IS ACTIVE = PDP DEPHOSPHORYLATES PDC AND PDK IS INHIBITED. AFTER CREATION OF ACETYL COA, PDK PHOSPHORYLATES PDC UNTIL MORE PYRUVATE NEEDS TO BE DECARBOXYLATED.
PDH is positively effected in a low energy/hungry state by ADP and pyruvate
PDH is negatively regulated in a fed state by NADH, acetyl CoA and ATP
Regulatory steps of TCA
There are three IRREVERSIBLE steps of TCA:
1) first rxn combining acetyl-CoA with oxaloacetate to form citrate via CITRATE SYNTHASE
2) third rxn converting 6C isocitrate to 5C alpha-ketoglutarate via isocitrate dehydrogenase is the RATE LIMITING STEP and produces NADH, H+ and CO2
3) the forth rxn converting 5C alpha-ketoglutarate to 4C succinyl-CoA via a-ketoglutarate dehydrogenase and releasing NADH and CO2.
Oxaloacetate in other pathways
OXA can be converted to malate (another TCA intermediate) which can be transported from the mito matrix to the cytosol and converted back into OXA which can be further converted into PEP and then eventually into glucose. OXA can also be converted into amino acids (Asp and Asn)
Citrate in other pathways
citrate can move out of the mito membrane without help and can be converted into acetyl-CoA in the cytoplasm which will eventually be used in FA synthesis
Where does oxidative phosphorylation take place?
the inner mitochondrial membrane
pH of mito inter-membrane space
low pH bc of the high [H+] ions used to feed ATP Synthase
pH of mito matrix
high pH bc of the low [H+]
what is the pmf
Proton-motive force: the proton/pH gradient/membrane potential between the inner membrane and the mito matrix, used to drive ATP synthase for ATP synthesis
Complex V of ETC
ATP Synthase converts ADP + Pi to ATP.
oligomycin disrupts the proton transport through ATP Synthase (inhibitor)
DRAW ETC complexes and locations and products
I: takes in NADH from mito matrix and releases a H+ into intermembrane space. Send electrons from NADH to CoQ (ubiquinone)
II: Sends electrons from FADH2 to CoQ.
III: releases [H+] into inter-membrane space. sends intermediates cytochrome-c
IV: releases [H+] into inter-membrane space and uses O2 to make H2O (sent to mito matrix)
V: uses the [H+] gradient to phosphorylate ADP > ATP and
inhibition of ETC
when transfer of electrons is inhibited >> decrease in protons pumped into inter-membrane >> decrease in proton gradient/proton-motive force >> inhibition of ATP synthase.
Malonate inhibits complex II
antimycin inhibits complex III
cyanide/CO/H2S inhibit complex IV
oligomycin inhibits V
operates in heart, liver and kidneys to move malate into mito matrix where it can feed into complex I in the ETC