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43 Cards in this Set
- Front
- Back
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Why does NADH yield more ATP than FADH2?
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Because NADH is oxidized by complex I and protons are generated whereas FADH2 enters the pathway further down at complex II and generates 4 less protons
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What effect does rotenone have on ox phos?
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Inhibits complex I and blocks e* transfer and also effects p-ways that require NAD(TCA cycle) because NADH is no longer being reduced
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Other inhibitors of ox phos include?
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MACO
Malonate II, Anitmycin A III, Cynaide IV, Oligomycin V or atp synthase Carbon monoxide also inhibts complex 4 |
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What other way can ox phos be inhibited?
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By uncoupling proteins or agents. 2,4-DNP and thermogenin
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How do brown and white adipose tissue?
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Brown tissue is more prevalent in infants and is loaded with mitochondria which is repsonible for generating heat "non-shivering" type. White has considerably less mitochondria
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What role do ROS play in the body?
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There is a delicate balance between their action in cell defense, antioxidants, enzymes and as free radicals.
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Is oxidative phosphorylation a major site of ROS production?
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Yes
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What are sources of free radicals?
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Coenzyme Q
Peroxisome NADPH oxidase Myeloperoxidase Ionizeing Radiation |
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What are free radicals?
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Superoxide
OH* OONO* NO* |
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Which free radical can act as neurotransmitter in normal state?
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Nitric Oxide
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What problems can be associated with ROS overproduction?
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Protein, Membrane, DNA, Mt Damage, Lipid peroxidation, Cell swelling, INflux Ca, Na, H2O cell swells
Know lipid and DNA damage..... can result in base pair change and possible mutation |
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Nitric oxide normal functions as NT, Hormone, Muscle contraction, signal transduction molecule but can be deleterious if overproduced. what pway results in NO produciton?
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Arginine -> Citrulline
NO is byproduct of rxn NO synthase is involved |
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ROS are us in normal defense of what and pway used to produce?
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Oxygen is used by NADPH oxidase to reduce it to NADP resulting in O*
Neutrophils use this byproduct to neutralize bacteria by with produciton of ONO |
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If a patient is deficient in NADPH oxidase possible consequences?
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Chronic Granulomous Disease CGD
NADPH Oxidase Deficiency |
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Name antioxidant enzymes?
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Super Oxide Dismutase, Catalase, Glutathione reductase, Glutathione Peroxidase, Viatmin E
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what occcurs during MI on molecular level?
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Loss of ox-phos, ^lactic acid, dec. ATP, dec. adenine nucleotide (Purine degrad. pway), ^calcium
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How does reperfusion injury result?
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Upon return of Oxygen the ox phos pway is overloaded and large increase of ROS produced.
Inhib. of ox-phos allows ubiquinone to form ubisemiubiauinone Mt perm. transition pore (MPTP) opens serving as uncoupler AND also allows cyt C to leak out of the mitochondria (APOPTOSIS) |
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How does mt DNA differ from nuclear DNA?
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Lacks histones, repair system, and has 10x mutation rate.
Maternal Inheritance |
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Mt myopathies include what clinical manifestations?
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Drooping eyelids, muscel weakness, GI upset, Liver failure, cardiomyopathy, and nervous system involvement (seizure, tremor, dementia).
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What happens when the ETC is decreased?
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Pyruvate and FA accumulate, Lactate acidosis, accum. TG, ATP syn decreased (muscle weakness, exercise tolerance, formation of ragged red fibers, due to increased mt proliferation
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What complex is affected in Leber's heriditary optic neuropathy (LHON)?
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COMPLEX I (point mutatn)
Pt presents with loss of vision (optic nerve death) Muscle biopsy normal NO ragged red fibers |
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What syndrome is inherited via a mutation in ATPase, severe clinical presentation at 1-2 yrs, with dev. delay, hypotonia, ataxia, spasticity, and respiratory defects?
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MILS- Maternally inherited leigh's syndrome
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What condition presents with MERRF? Onset in early childhood or adult. Muscles have RRF and are COX deficient. Most frequent mutations occurs in the lysine tRNA gene?
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MERRF= Myoclonus Epilepsy with Ragged Red Fibers
Myoclonus siezures cerebellar ataxia, myopathy |
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Mt myopathies include what clinical manifestations?
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Drooping eyelids, muscel weakness, GI upset, Liver failure, cardiomyopathy, and nervous system involvement (seizure, tremor, dementia).
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What happens when the ETC is decreased?
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Pyruvate and FA accumulate, Lactate acidosis, accum. TG, ATP syn decreased (muscle weakness, exercise tolerance, formation of ragged red fibers, due to increased mt proliferation
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What complex is affected in Leber's heriditary optic neuropathy (LHON)?
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COMPLEX I (point mutatn)
Pt presents with loss of vision (optic nerve death) Muscle biopsy normal NO ragged red fibers |
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What syndrome is inherited via a mutation in ATPase, severe clinical presentation at 1-2 yrs, with dev. delay, hypotonia, ataxia, spasticity, and respiratory defects?
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MILS- Maternally inherited leigh's syndrome
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What condition presents with MERRF? Onset in early childhood or adult. Muscles have RRF and are COX deficient. Most frequent mutations occurs in the lysine tRNA gene?
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MERRF= Myoclonus Epilepsy with Ragged Red Fibers
Myoclonus siezures cerebellar ataxia, myopathy |
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What symptoms are linked with Parkinsons disease?
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Bradykinesia, rigidity, tremor, degeneration of dopaminergic neurons. Primary substantia nigra ars compacta (SNc)
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What chemical when administered to people would result in Parkinson's like symptoms?
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MPTP
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What results can oxidative stress have on SNc?
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Dopamine oxidation H2O2 and ROS
Reason SNC most severe damage Cell death results from increased dopamine turnover, deficiency of glutathione, increased in reactive Fe, and greater production of ROS due to complex I defeciency |
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What does the free radical insuate about Parkinson's disease cuasuality?
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30-40% reduction in complx I actvity
PD results in defect in mt genome PD pt show selecitve decrease in glutathione (result of lewy bodies) |
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What is usually found in PD pt to suggest oxidative damage?
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Lipid peroxidation found in SNc but not cerebellum, protein arbonyls increased, 8-hydroxy-2-d-guanosine found within PD pt (DNA adduct), decreased glutathione activity, SNc dopaminergic neurons are rich in glutmate R, increase in intracell Ca activates NO sythase to from NO
NO plus superoxide forms peroxynitrite ONOO & OH NO damages ETC and no GSH to prevent SNc MPTP toxicity is lowwered in NOS KO mice |
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What complex does rotenone effect?
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complex I mimics Parkinson's disease so used in induction of models
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What is function of Complex I?
Composition? |
Is NADH-CoQ Reductase
It uses FMN flavin mononucleotide, then series of Iron-Sulfur rings to transport electrons to CoQ (ubiquinone). |
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What is function of Complex II? Composition?
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Succinate Dehydrogenase or Succinate-CoQ reductase. Only E that is in TCA and ETC.
FAD and FE-S groups |
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What is function of Complex III? Composition?
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CoQH-cyt c reductase or Ubiquinol-cyt c
Heme, Fe-S |
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Function of cyt C?
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Soluble transmembrane protein in the inner membrane of mt. Transfers proteins from complex III cyt c reductase to complex IV cyt c oxidase
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Funciton of IV?
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Cytochrome C oxidase. Recieves e* from cyt c and transfers them to Oxygen to make water.
Heme |
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ATP synthase structure?
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Consists of two regions:
Fo-pore in the membrane in which protons flow back into matrix F1-headpiece and is found in matrix, 3 alpha, 3 beta su, 1 gamma subunit in center There is a stalk that attaches to a non-moving portion of Fo that prevents F1 a and B su from moving. The gamma su rotates with Fo. There are three nucleotide binding sites |
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What enzyme of ETC does oligomycin inhibit?
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ATP Synthase- the Fo portion transmembrane
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Inhibitors of ox phos?
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R-MACC
rotenone malonate antimycin a cyanide and CO |
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What mechanism causes most damage in reperfusion injury?
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Mt permeability transition pore (MPTP) opens to serve as an uncoupler to ox-phos and allows CYTOCHROME C to leak out of the mt causing APOPTOSIS
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