Transcript Ubiquinone
Oxidative phosphorylation NADH transport Oxidative phosphorylation p691 Only those with specific transporters can pass N side All pathways related to fuel oxidation except glycolysis Oxidative phosphorylation • Converting the energy from electrons (from NADH and FADH2) to ATP Five electron carrying molecules 1. NAD+ 2. FAD 3. Ubiquinone 4. Cytochromes 5. Iron-sulfur proteins Ubiquinone (coenzyme Q; Q; Q10) Ubiquinone Plastoquinone (plant chloroplast) Menaquinone (bacteria) p693 cytochromes p694 Iron-sulfur proteins p695 Method for determining the sequence of electron carriers A B C D E F A B C D E F A B C D E F p696 p698 Chemical uncouplers p707 • Chemicals like DNP and FCCP are weak acid with hydrophobic properties that permit them to diffuse readily across mitochondrial membranes. After entering the matrix in the protonated form, they can release a proton, thus disspating the proton gradient. p406 Ionophores • Valinomycin (an ionophore) allows inorganic ions to pass easily through membranes. This will uncouple electron transfer from oxidative phosphorylation. p696 Complex I p698 Complex I & II p697 Complex III p700 Complex IV p702 NADH Mitochondrial intermembrane space FADH2 Cyt c Mitochondrial inner membrane Qe I NAD+ Mitochondrial matrix III eII FAD e NADH H+ H+ H+ H+ e e FADH2 IV O H+ H2O H+ H+ H+ H+ H+ H+ H+ p703 p675 Mitochondrial ATP synthase complex p711 Oxidative phosphorylation in brown fat tissue is uncoupled with ATP synthesis p687 Regulation p718 NADH transport • NADH produced by glycolysis must be transported into mitochondria to produce ATP. • However, NADH cannot enter mitochondria directly. Instead it is transported by the form of malate or glycerol 3-phosphate. Malate-aspartate shuttle NADH NAD+ p715 Malate OAA NADH dehydrogenase Malate NAD+ malate dehydrogenase OAA Glutamate Aspartate Aspartate a-KG aminotransferase Aspartate aminotransferase Glycerol 3-phosphate shuttle p715 NADH Glycolysis Cytosolic glycerol 3Glycerol 3phosphate NAD+ phosphate dehydrogenase DHAP FADH2 DHAP FAD Q III DHAP Glc G6P F6P F1,6BP NADH G3P 1,3BPG 3-PGA 2-PGA PEP NADH Malateaspartate shuttle NADH Pyruvate Glycerol 3phosphate shuttle FADH2 Mitochondrial genome p720 Mitochondrion is probably evolved from endosymbiotic bacteria p35 Mitochondrial encephalomyopathies • Mutations in mitochondrial genes cause mitochondrial encephalomyopathies that affecting primarily the brain and skeletal muscle. Because infants inherit their mitochondria from their mothers, so mitochondrial encephalomyopathies are maternal-linked. Leber’s hereditary optic neuropathy (LHON) • LHON is the result of defective mitochondrial genes that are involved in electron transfer. • Vision loss usually occurs between the ages of 15 and 35. Myoclonic epilepsy and raggedred fiber disease (MERRF) • Mutation in the mitochondrial gene that encodes a tRNA specific for lysine (lysyl-tRNA) results in MERRF. • Synthesis of several proteins require this tRNA is interrupted. p720 MERRF • MERRF patients often have abnormally shaped mitochondria containing paracrystalline structures. • This lysyl-tRNA mutation is also one of the causes of adult-onset (type II) diabetes. Many respriatory proteins are encoded by mitochondria Bacteria do have respiratory chain enzymes • For example, E. coli has NAD-linked electron transfer from substrate to O2, coupled to the phosphorylation of cytosolic ADP. Mitochondria, apoptosis, and oxidative stress Mitochondria is not only involved in ATP synthesis. It is also involved in cellular damage and death. The role of mitochondria in apoptosis • When cell receives a signal for apoptosis, one consequence is the permeability of the outer mitochondrial membrane will increase, allowing cytochrome c release. • The release of cytochrome c will activate caspase 9, which will initiate the protein degradation process. Mitochondria can produce superoxide free radical