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Evolution of Oxygen Levels in Earth’s Atmosphere. Carboniferous. Jurassic. Volume % Oxygen. Cenozoic era. Permian. Cambrian. Precambrian . Ordovician. Devonian. Silurian. Triassic. Millions of Years before Present. Evolution of Oxygen Levels in Earth’s Atmosphere. Carboniferous.
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Evolution of Oxygen Levels in Earth’s Atmosphere Carboniferous Jurassic Volume % Oxygen Cenozoic era Permian Cambrian Precambrian Ordovician Devonian Silurian Triassic Millions of Years before Present
Evolution of Oxygen Levels in Earth’s Atmosphere Carboniferous Jurassic Volume % Oxygen Cenozoic era Permian Cambrian Precambrian Ordovician Devonian Silurian Triassic Millions of Years before Present
Why is oxygen important? Glycolysis Glucose + 2 NAD+ + 2 Pi + 2 ADP → 2 pyruvate+ 2 NADH + 2 ATP + 2 H+ + 2 H2O + heat Oxidativephosphorylation
Mitochondria and oxygen Electron transport chain Q cytochrome c reductase (complex III) produces a radical intermediate and can be leaky releasing electrons in the cell
The leaky system produces Reactive Oxygen Species that include:superoxide, hydrogen peroxidehydroxyl radicals Evolution has coopted some as important signaling molecules: • Hydrogen peroxide • Nitric oxide • Hydrogen sulfide • Carbon monoxide
Valency flexibility • Sulfur • Phosphorus • Selenium • Nitrogen
Atomic Number:16 Atomic Radius: 104 pm Atomic Weight:32.06 Electron Configuration: [Ne]3s23p4 Oxidation States: 6, 4, 2, -2 # cysteines in genome Biological complexity 200,000 cysteines in human proteome
Nitrogen Atomic Number:17Covalent Radius: 71 pm Atomic Weight:14.01 Electron Configuration:[He] 2s22p3 2, 5Oxidation States: 5, 4, 3, 2, 1, −1, −2, −3 Nitric Oxide
Atomic Number:34 Atomic Radius: 120 pm Atomic Weight:78.97 Electron Configuration:[Ar] 3d10 4s24p4 2, 8, 18, 6 Oxidation States: 6, 4, 2, 1, -2
Atomic Number:15 Atomic Radius: 107 pm Atomic Weight:30.97 Electron Configuration:[Ne] 3s23p3 2, 8, 5 Oxidation States: 5, 4, 3, 2, 1, −1, −2, −3 0.7 kg of phosphorus Human genome has ~500 protein kinase genes (2% of genome]. ~30% of all proteins may be modified by kinases, regulating many signal transduction pathways.
Cycles provide regulatory control Post-translational alterations in signaling proteins can add a layer of regulatory control. Two examples of which are: • Kinase and phosphatases • Glutathione S-transferases and glutaredoxins • These pathways can control cell growth/division and as such make logical targets for pharmaceutical interventions
Some examples of drug targets • Sulfur - protein folding machinery • Phosphorus - protein kinases • Nitrogen – nitric oxide vasodilators • Selenium – chemoprevention in cancer