Lecture 6 - Oxidative phosphorylation and Mitochondrial Function Flashcards
What are the two glycolytic enzymes that perform substrate level phosphorylation?
1) Phosphoglycerate kinase
2) Pyruvate kinase
Cause & symptoms of pellagra
Cause: Niacin (B3) deficiency
Symptoms: Dermatitis, dementia, diarrhea (3Ds for B3)
What does NADH accept when reduced?
2e- and H+
a hydride
What does FADH2 accept when reduced?
2 e- and H+
List the complexes of the electron transport system.
1) NADH Dehydrogenase
2) Succinate-Q reductase
3) Cytochrome bc1 complex (complex III)
4) Cytochrome c oxidase (complex IV)
Mobile carriers:
CoQ (carries 2e-, 2H+), Cytochrome C (1e-)
Protein molecules that contain heme with an iron atom
Cytochromes (1e- carriers that are fixed)
Proteins that contain Fe and S in a cluster
Fe-S, 2Fe-2S, 4Fe-4s (1e- carriers that are fixed)
Copper containing cytochrome
Cytochrome C oxidase (1e- carriers that are fixed)
How many Protons must pass through ATP synthase to produce an ATP?
4
How many protons are pumped into the inter membrane space by each ETC complex.
1) Complex I (NADH DH) - 4
2) Complex II (Succinate DH) - 0
3) Complex III (Cytochrome b-c1 complex) - 4
4) Complex IV (Cytochrome c oxidase) - 2
What agents inhibit complex I?
Rotenone and amytal
What agents inhibit complex III?
Antimycin A
What agents inhibit complex IV?
CN-, N3-, CO
What is the primary indicator of prolonged defects in oxidative phosphorylation?
Lactate accumulation
What is the significant of dinitrophenol?
It is an uncoupler of electron transport. It is lipophilic and can pass back and fourth between the matrix and inter membrane space, shuttling protons down their gradient and back into the matrix. This is bad!
UCP1
Uncoupling protein one (thermogenin) is a channel that inserts in the inner membrane of the mitochondria and allows protons to flow back down their gradient into the matrix.
LOHN (symptoms and cause)
Symptoms: Bilateral subacute optic neuropathy (blindness) effects men but not women. Cause: Mt DNA mutation in complex I - 95% of cases)
MELAS (symtoms and cause)
Symptoms: Mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes. Cause: mt DNA mutation in tRNA Leu - 80%)
Leigh syndrome (symptoms and cause)
Symptoms: Developmental delay, ataxia, blindness, seizures, lactic acidosis Cause: mt DNA and nuclear genes required for electron transport or PDH complex.
MERRF (symptoms and cause)
Symptoms: Myoclonic epilepsy with ragged red fibers (myopathy, ataxia, blindness). Cause: mt tRNA Lys
