Block 2 OXPHOS Flashcards
What is anaerobic respiration?
The first phase of OXPHOS, in which ox of fuels transfers e- to NAD+ and FAD
What is oxidative phosphorylation?
Energy from NADH and FADH2 and red of O2 to H2O –> high energy P bonds of ATP
What is chemiosmotic hypothesis?
Proton gradient across IMM established by ETC provides energy for ATP synthesis
What are the pHs of the mitochondrial cytosol and matrix? What accounts for this difference?
Cyt: 6.88; Mat: 7.78
Due to the proton gradient established by the ETC
What is complex 1 of the ETC, and what does it do?
NADH DH, converts NADH + H+ to NAD+, pumps out 4 H+, and transfers e- to CoQ
What is complex 2 of the ETC, and what does it do?
Succinate DH, converts succinate to fumarate, transfers e- to CoQ
What is complex 3 of the ETC, and what does it do?
Cytochrome b-c1, pumps out 4 H+, accepts e- from CoQ and transfers e- to cytochrome C
What is complex 4 of the ETC, and what does it do?
Cytochrome oxidase, converts 2H+ + ½ O2 to H2O, accepts e- from cytC, pumps out 2 H+
What is complex 5 of the ETC, and what does it do?
ATP synthase, uses 4H+ flowing into the matrix to convert ADP + Pi to ATP
Altered functioning of which ETC complex may contribute to PD, SZ, and diabetes?
Complex 1, NADH DH
Altered functioning of which ETC complex is commonly seen in paraganglioma cancer? What is special about this complex?
Complex 2, succinate DH
This is the only ETC complex encoded only by nuclear DNA
Altered functioning of which ETC complex may contribute to AD and maybe hypoxic cancer cells?
Complex 4, cytochrome oxidase
Which ETC complex may be found on the surface of some cancer cells?
Complex 5, ATP synthase
Which ETC complex uses prosthetic groups Fe-S and heme b & c, and is inactivated by antimycin, demerol, and Fe deficiency?
Complex 3, cytochrome b-c1 complex
Which ETC complex uses prosthetic groups FAD and Fe-S and is inactivated by malonate?
Complex 2, succinate DH
Which ETC complex uses prosthetic group heme c and is inactivated by Fe deficiency?
Cytochrome C
Which ETC complex uses prosthetic groups FMN and Fe-S and is inactivated by rotenone and riboflavin deficiency?
Complex 1, NADH DH
Which ETC complex uses prosthetic groups heme a and Cu, and is inactivated by cyanide, CO, ischemia, Fe/Cu deficiency?
Complex 4, cytochrome oxidase
Which ETC complex uses prosthetic group CoQ and is inactivated by generation of free radicals and doxorubicin?
Coenzyme Q/ubiquinone
What is an Fe-S center?
Prosthetic groups with 2,3,4,8 Fe atoms and cysteine sulfur atoms, which hold groups in place within protein and provide sulfur ligands
Why might patients with iron deficiency anemia experience fatigue?
The Fe-S centers and Fe-containing cytochromes in ETC are also Fe-deficient, leading to lack of e- transport for ATP production
How does doxorubicin work?
Binds cardiolipin, inhibits succ ox, inhibits ATP synthase, forms free radicals
What is Reye’s syndrome?
Following URI, chicken pox, use of aspirin impairs energy metabolism, resulting in inability to incorporate ammonia into urea –> hepatic coma
How much energy liberated during complete oxidation of glucose is recaptured by glycolysis and OXPHOS?
30%
What are chemical uncouplers? What is an example?
Proton ionophores that carry H+ across membranes, allowing PMF to collapse; salicylate (degradation product of aspirin)
What is thermogenin?
A natural uncoupler that promotes generation of heat, stimulated by norepi
How does thyroid hormone affect OXPHOS?
Unclear; effectively uncouples OXPHOS, and decreases efficiency of energy derivation from fuel, results in increase in heat production
What is creatine kinase?
Forms creatine phosphate, which stores P for quick transfer to ADP when ATP needed for muscle contraction
What are the components of the mitochondrial permeability transition pore (mPTP)?
ANT (IMM) regulated by cyclophilin D binds VDAC (OMM), which binds Bcl2 and Bax
How does the glycerol-phosphate shuttle work?
DHAP + NADH –> glycerol-3-P + NAD+ by cytosolic G3P DH. Mito G3P DH makes FADH2, transfers to QH2 and regenerates DHAP
How does the malate-aspartate shuttle work?
Malate carries H from NADH into matrix, converts to OAA with loss of H, OAA –> a-kg by glutamate –> aspartate (and reverse in cytoplasm)
Where are the glycerol-phosphate and malate-aspartate shuttles located?
G-P: skeletal muscle, brain
M-A: liver, kidney, heart
How many ATP molecules can be synthesized from a pair of electrons using each of the shuttles?
G-P shuttle: 1.5 ATP because of e- transfer to FADH2
M-A shuttle: 2.5 ATP
What is the main mechanism underlying mitochondrial dysfunction disorders?
Accumulation of ROS and mtDNA damage
What is a cybrid? What is it useful in testing for?
Immortal cell de-mito’ed + denucleated patient fibroblast. If mito function normal, nuclear problem. If mito fxn abnormal, mito problem.
