From the Guidelines
Oxidative phosphorylation is the process by which cells generate adenosine triphosphate (ATP) via aerobic respiration, and it is crucial for meeting the energy demands of most cells in our bodies. This process occurs in the mitochondria, specifically on the inner mitochondrial membrane, and represents the final stage of cellular respiration 1. During oxidative phosphorylation, electrons from NADH and FADH2 are transferred through a series of protein complexes called the electron transport chain. As electrons move through this chain, they release energy that is used to pump protons (hydrogen ions) across the membrane, creating a concentration gradient. This gradient drives the enzyme ATP synthase, which harnesses this potential energy to synthesize ATP from ADP and inorganic phosphate. Some key points about oxidative phosphorylation include:
- It is the primary function of mitochondria, which are double-membrane bound, intracellular organelles present in all cells except erythrocytes 1
- Mitochondria also host several other metabolic pathways, including the tricarboxylic acid (TCA) cycle, urea cycle, β-fatty acid oxidation, and lipid and cholesterol synthesis 1
- Impairment of the respiratory chain involved in oxidative phosphorylation can lead to mitochondrial disorders 1 Oxidative phosphorylation is remarkably efficient, producing significantly more ATP than earlier metabolic processes like glycolysis. Oxygen serves as the final electron acceptor in this process, combining with electrons and protons to form water, which is why we need to breathe oxygen - it's essential for this energy-producing pathway.
From the Research
Definition of Oxidative Phosphorylation
- Oxidative phosphorylation is a process in which the mitochondrial electron transport chain generates cellular ATP through a series of electron transfer reactions 2.
- It is a crucial mechanism for producing energy in higher animals and plants, responsible for setting and maintaining metabolic homeostasis 3.
Mechanism of Oxidative Phosphorylation
- The process involves the transfer of reducing equivalents from the intramitochondrial [NAD+]/[NADH] pool to molecular oxygen, with irreversible reduction of oxygen to bound peroxide at cytochrome c oxidase determining the net flux 3.
- Cytochrome c oxidase is responsible for reduction of molecular oxygen to water using reducing equivalents donated by cytochrome c and for site 3 energy coupling in oxidative phosphorylation 4.
Regulation of Oxidative Phosphorylation
- The rate of oxidative phosphorylation is determined by demand for ATP, with feedback by the energy state ([ATP]/[ADP][Pi]) regulating the pathway 3.
- The regulatory center of mitochondrial oxidative phosphorylation is cytochrome c oxidase (COX), which is regulated through binding of various effectors to its "supernumerary" subunits, by reversible phosphorylation, and by expression of subunit isoforms 5.
- COX is also subject to feedback inhibition by ATP, the final product of OXPHOS, which maintains a low and healthy mitochondrial membrane potential and prevents the formation of ROS 5.