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When carbon is oxidized during the respiratory process of a terrestrial organism, it becomes the gas carbon dioxide – a waste material that is easy for a creature to remove from its body. The oxidation of silicon, however, yields a solid because, immediately upon formation, silicon dioxide organizes itself into a lattice in which each silicon atom is surrounded by four oxygens. Disposing of such a substance would pose a major respiratory challenge.

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Life-forms must also be able to collect, store, and utilize energy from their environment. In carbon-based biota, the basic energy storage compounds are carbohydrates in which the carbon atoms are linked by single bonds into a chain. A carbohydrate is oxidized to release energy (and the waste products water and carbon dioxide) in a series of controlled steps using enzymes. These enzymes are large, complex molecules (see proteins) which catalyze specific reactions because of their shape and "handedness." A feature of carbon chemistry is that many of its compounds can take right and left forms, and it is this handedness, or chirality, that gives enzymes their ability to recognize and regulate a huge variety of processes in the body. Silicon's failure to give rise to many compounds that display handedness makes it hard to see how it could serve as the basis for the many interconnected chains of reactions needed to support life.

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The absence of silicon-based biology, or even silicon-based prebiotic chemicals, is also suggested by astronomical evidence. Wherever astronomers have looked – in meteorites, in comets, in the atmospheres of the giant planets, in the interstellar medium, and in the outer layers of cool stars – they have found molecules of oxidized silicon (silicon dioxide and silicates) but no substances such as silanes or silicones which might be the precursors of a silicon biochemistry.