The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

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An Introduction to Mitochondria Fig. 2.3. Varieties of glycolysis 13
14 The Mitochondrial Free Radical Theory of Aging already in the matrix. This is mainly done by a group of enzymes and carriers collectively termed the malate/aspartate shuttle. There is also a backup pathway for transfer of electrons from cytosolic NADH to the mitochondrial ATP synthesis machinery. It is much simpler, involving no matrix-located components and only two enzymes. Its disadvantage is that it is less energy-efficient than the malate/aspartate shuttle. Muscles that work extremely hard for short durations (such as insect flight muscles) use it a great deal. 13 It is called the s,n-glycerophosphate shuttle. Also, since ATP (over and above that created by glycolysis) is needed throughout the cell and not only in mitochondria, it must be transported out of mitochondria after being made, and conversely its constituent parts, ADP and phosphate, must be imported. These processes are also done by specialised carrier proteins: ATP and ADP by one, and phosphate by another. The only other metabolites that need to cross the membrane are oxygen (which is consumed by the processes described in the rest of this section) and carbon dioxide (which is generated by those processes); they both cross it quite freely, like water, without an active carrier. 2.3.3. Mitochondrial Chemistry 2.3.3.1. Creation of Acetaldehyde, as Acetyl CoA: Oxidation The first degradative process that occurs inside mitochondria is the conversion of pyruvate and fatty acids to acetaldehyde. These are oxidation reactions, because they involve the removal of electrons from the major reagents. This process does not make ATP, and there is no hugely compelling reason why it should not have evolved to happen in the cytosol. Ostensibly that would have been simpler, because then only one molecule destined for destruction—acetaldehyde—would need to be imported into mitochondria, as against two different, larger ones (pyruvate and fatty acids). The likely reason is that, whereas pyruvate and fatty acids diffuse freely in the cytosol, acetaldehyde is always attached to a carrier molecule, coenzyme A (CoA), which is quite large (see Fig. 2.4) and is not transported through the mitochondrial membrane. Both fatty acid oxidation and pyruvate oxidation end by attaching a molecule of acetaldehyde to CoA, forming acetyl CoA. 14,15 The attachment involves the liberation of two hydrogen atoms, whose constituent protons and electrons go to the usual reservoirs. 2.3.3.2. More ATP, but on Borrowed Oxygen: Oxidation (Again) Acetaldehyde contains two carbon atoms, one oxygen and four hydrogens, and in mitochondria it is converted into two molecules of carbon dioxide. Clearly this needs a supply of three atoms of oxygen for each molecule of acetaldehyde. But this is not where the oxygen we breathe is used: that comes later. Instead, the oxygen is recruited by breaking down three molecules of water. The other imbalance between acetaldehyde and carbon dioxide is the hydrogens. The conversion of one molecule of acetaldehyde and three of water to two of carbon dioxide releases ten of them. Two of these have already been accounted for by the attachment of acetaldehyde to CoA; the other eight are released now. All ten go to the reservoirs—ten protons into the aqueous medium, and ten electrons into five two-electron carriers, which is this case are four NADH and one FADH2. The breakdown of acetaldehyde is done by a complex series of reactions (see Fig. 2.5) that was worked out in the 1930s. The key breakthrough, identification of the cyclic nature of this series, was achieved in 1937 by Hans Krebs, 16,17 which is why it is often called the Krebs cycle. Krebs preferred to call it the tricarboxylic acid (TCA) cycle, so I will stick to that term.
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Page 3 and 4: ISBN: 1-57059-564-X MOLECULAR BIOLO
Page 5 and 6: 7. The Status of Gerontological The
Page 7 and 8: 17. Conclusion: The Role of the Ger
Page 9 and 10: I cannot overstate my profound grat
Page 11 and 12: CHAPTER 1 Introduction 1.1. What Is
Page 13 and 14: Introduction Some may feel that all
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Page 27 and 28: 18 Fig. 2.7. The respiratory chain.
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History of the Mitochondrial Free R
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CHAPTER 7 The Status of Gerontologi
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The Status of Gerontological Theory
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The Status of Gerontological Theory
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CHAPTER 8 The Search for How Mutant
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The Search for How Mutant mtDNA is
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CHAPTER 9 The Search for How So Few
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The Search for How So Few Anaerobic
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CHAPTER 10 Frequently-Asked Questio
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Frequently-Asked Questions The effe
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Frequently-Asked Questions Table 10
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Frequently-Asked Questions through
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Frequently-Asked Questions has been
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Frequently-Asked Questions SOS, sin
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Frequently-Asked Questions for almo
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Frequently-Asked Questions Fig. 10.
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Frequently-Asked Questions Fig. 10.
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Frequently-Asked Questions of elect
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Frequently-Asked Questions Referenc
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Frequently-Asked Questions 45. Clay
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CHAPTER 11 A Challenge from Textboo
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A Challenge from Textbook Bioenerge
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160 The Mitochondrial Free Radical
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CHAPTER 14 Ablation of Anaerobic Ce
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Ablation of Anaerobic Cells: Techni
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CHAPTER 15 Transgenic Copies of mtD
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Transgenic Copies of mtDNA: Techniq
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CHAPTER 16 Prospective Impact on th
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Prospective Impact on the Healthy H
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Prospective Impact on the Healthy H
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Index Symbols “~”, 19 A Acetald
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Index Copper 35, 107 see also trans
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Index Heart comparison to man-made
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Index genetic code 23, 115-118, 177
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Index Perhydroxyl radical 41, 122,
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Index protonation see protonation (
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MOLECULAR BIOLOGY INTELLIGENCE UNIT
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