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P691 Only those with specific transporters can pass All pathways related to fuel oxidation except glycolysis N side.

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Presentation on theme: "P691 Only those with specific transporters can pass All pathways related to fuel oxidation except glycolysis N side."— Presentation transcript:

1 p691 Only those with specific transporters can pass All pathways related to fuel oxidation except glycolysis N side

2 Oxidative phosphorylation Converting the energy from electrons (from NADH and FADH 2 ) to ATP Electron transfer occurs in oxidative phosphorylation: 1. Direct transfer to reduce cation, Fe 3+  Fe Transfer as hydrogen atom 3. Transfer as hydride ion (:H - )

3 1. NAD + 2. FAD 3. Ubiquinone 4. Cytochromes 5. Iron-sulfur proteins Five electron carrying molecules

4 Ubiquinone (coenzyme Q; Q) Ubiquinone Plastoquinone (plant chloroplast) Menaquinone (bacteria) p693

5 p694 cytochromes

6 Iron-sulfur proteins p695 Iron-sulfur proteins

7 Method for determining the sequence of electron carriers p696

8

9 p705 Oxidative phosphorylation

10 p698 Complex I NADH +H + +Q --> NAD++QH 2 4 protons pump out NADH +H + FMN Fe 2+ SCoQ NAD + FMNH 2 Fe 3+ SCoQH 2

11 p697 Complex I & II Succinate FAD Fe 2+ S CoQ Fumarate FADH 2 Fe 3+ S CoQH 2

12 p700 Complex III QH 2 +2Cytc 1 oxidized +2H N + --> Q+2Cytc 1 reduced +4H p + CoQH 2 cyt b ox Fe 2+ S cyt c 1 ox cytc red CoQ cytb red Fe 3+ S cytc 1 red cytc ox

13 p702 Complex IV 4Cytc reduced +8H N + +O 2 --> 4Cytc oxidized + 4H p + +2H 2 O cyt c red cyt a ox cyt a 3 red O 2 cyt c ox cyt a red cyt a 3 ox 2 H 2 O

14 p703

15

16 p706 QH 2 oxidase (resistant to cyanide)

17 p675

18 p698

19 Chemical uncouplers 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. p707

20 Ionophores Valinomycin (an ionophore) allows inorganic ions to pass easily through membranes. This will uncouple electron transfer from oxidative phosphorylation. p406

21 p711 Mitochondrial ATP synthase complex

22 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.

23 p715 Malate-aspartate shuttle

24 p715 Glycerol 3-phosphate shuttle

25 p687 Oxidative phosphorylation in brown fat tissue is uncoupled with ATP synthesis

26 p718 Regulation

27

28 p720 Mitochondrial genome

29 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.

30 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.

31 Myoclonic epilepsy and ragged- red 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.

32 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.

33 Many respriatory proteins are encoded by mitochondria

34 p35 Mitochondrion is probably evolved from endosymbiotic bacteria

35 Bacteria do have respiratory chain enzymes For example, E. coli has NAD-linked electron transfer from substrate to O 2, coupled to the phosphorylation of cytosolic ADP.

36 Mitochondria, apoptosis, and oxidative stress Mitochondria is not only involved in ATP synthesis. It is also involved in cellular damage and death.

37 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.

38 Mitochondria can produce superoxide free radical

39 Mitochondria and oxidative stress Antimycin A inhibits complex III by occupying the Q N site, which may increase the likelihood of superoxide radical formation and cellular damage.

40 The role of mitochondria in oxidative stress PPP


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