Abstract
O(2) is essential for the maintenance and growth of aerobic animals, similar to the essentiality of what are classically considered nutrients. Nevertheless, O(2) is not customarily regarded as a nutrient, this reflecting the route by which it enters the body - through the lungs or gills in vertebrates, rather than via the mouth and gastrointestinal tract. A relative deficiency of O(2) occurs at high altitudes and during deep-sea diving, to which distinct adaptations occur. Deficiency is also evident in lung diseases such as emphysema. Without O(2), mitochondrial respiration and oxidative phosphorylation cannot take place. At a molecular level, cells adapt to O(2) deficiency by switching from oxidative metabolism to anaerobic glycolysis and there are changes in the expression of a multiplicity of genes, driven by hypoxia-sensitive transcription factors, particularly hypoxia-inducible factor-1. It is argued that O(2) should be fully included within the remit of nutritional science alongside the other essential macronutrients.