Oxygen - the forgotten nutrient

Abstract

O₂ is essential for the maintenance and growth of aerobic animals, similar to the essentiality of what are classically considered nutrients. Nevertheless, O₂ 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 O₂ 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 O₂, mitochondrial respiration and oxidative phosphorylation cannot take place. At a molecular level, cells adapt to O₂ 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 O₂ should be fully included within the remit of nutritional science alongside the other essential macronutrients.

Keywords: HIF, hypoxia-inducible factor; Hypoxia; Hypoxia-inducible factor-1; Oxygen deficiency; Oxygen utilisation; pO2, O2 tension.

Fig. 1.

Schematic illustration of the key cellular responses to oxygen deficiency based on white adipocytes. The effect of low oxygen tension on gene expression, glucose uptake and utilisation, lipid metabolism and the production of selected adipokines is shown. PAI-1, plasminogen activator inhibitor-1; angptl4, angiopoietin-like protein-4; VEGF, vascular endothelial growth factor; MMP, matrix metalloproteinases; FA, fatty acid; HIF-1, hypoxia-inducible factor-1; TF, transcription factors (additional to HIF-1, hypoxia-inducible factor-1); GLUT1, facilitative glucose transporter 1; MCT1, monocarboxylate transporter-1.