Page last updated: 2024-10-24

regulation of oxidative phosphorylation

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the phosphorylation of ADP to ATP that accompanies the oxidation of a metabolite through the operation of the respiratory chain. Oxidation of compounds establishes a proton gradient across the membrane, providing the energy for ATP synthesis. [GOC:dph]

Oxidative phosphorylation (OXPHOS) is a fundamental metabolic process that generates adenosine triphosphate (ATP), the primary energy currency of cells. This intricate process involves a series of tightly regulated steps occurring in the mitochondria, often referred to as the "powerhouse of the cell."

The regulation of OXPHOS is a complex interplay of multiple factors, ensuring that ATP production meets cellular demands while preventing harmful side effects:

**1. Substrate Availability:** The availability of substrates for OXPHOS, namely NADH and FADH2 generated from glycolysis and the citric acid cycle, directly influences the rate of ATP production. Increased substrate levels stimulate electron transport and ATP synthesis, whereas limited substrates reduce OXPHOS activity.

**2. Electron Transport Chain (ETC) Activity:** The ETC, embedded in the mitochondrial inner membrane, is responsible for transferring electrons from NADH and FADH2 to molecular oxygen, generating a proton gradient across the membrane. This gradient drives ATP synthesis by ATP synthase. Various factors regulate ETC activity:

* **Redox State:** The redox state of ETC components, such as cytochrome c, influences electron flow. High levels of reduced components promote electron transfer and ATP production.
* **Oxygen Availability:** Oxygen is the final electron acceptor in the ETC. Limited oxygen availability slows down electron transport and ATP synthesis.
* **Inhibitors:** Certain molecules, such as cyanide and carbon monoxide, inhibit ETC activity by binding to specific ETC components, disrupting electron flow and ATP synthesis.

**3. ATP Synthase Activity:** ATP synthase, also located in the inner membrane, utilizes the proton gradient generated by the ETC to synthesize ATP. Factors influencing ATP synthase activity include:

* **Proton Gradient Strength:** A stronger proton gradient drives more ATP synthesis.
* **ATP/ADP Ratio:** High ATP levels inhibit ATP synthesis, while low ATP levels stimulate it.
* **Uncouplers:** Molecules like 2,4-dinitrophenol disrupt the coupling between proton transport and ATP synthesis, allowing for electron flow without ATP production.

**4. Cellular Signaling Pathways:** Complex cellular signaling pathways regulate OXPHOS in response to various stimuli, such as nutrient availability, growth factors, and stress.

* **AMP-activated protein kinase (AMPK):** AMPK is activated during energy depletion and stimulates OXPHOS by promoting glucose uptake and fatty acid oxidation, increasing substrate availability.
* **Insulin and Glucagon:** These hormones regulate glucose metabolism and indirectly influence OXPHOS by affecting substrate availability.
* **Calcium Signaling:** Calcium ions play a role in regulating mitochondrial function, including OXPHOS.

**5. Mitochondrial Biogenesis:** The number and activity of mitochondria, the sites of OXPHOS, can be dynamically adjusted to meet cellular energy demands. This process, known as mitochondrial biogenesis, is regulated by various transcription factors and signaling pathways.

**6. Reactive Oxygen Species (ROS) Production:** The ETC is a significant source of ROS, which can have both beneficial and harmful effects. The cell tightly regulates ROS production to maintain a balance between beneficial signaling and oxidative stress.

In summary, the regulation of OXPHOS involves a complex interplay of various factors, ensuring optimal ATP production while maintaining cellular homeostasis. This intricate process is essential for cell survival and function.'
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Proteins (1)

ProteinDefinitionTaxonomy
Serine hydroxymethyltransferase, mitochondrialA serine hydroxymethyltransferase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:P34897]Homo sapiens (human)

Compounds (9)

CompoundDefinitionClassesRoles
oxaprozinoxaprozin : A monocarboxylic acid that is a propionic acid derivative having a 4,5-diphenyl-1,3-oxazol-2-yl substituent at position 3. It is non-steroidal anti-inflammatory drug commonly used to relieve the pain and inflammatory responses associated with osteoarthritis and rheumatoid arthritis.

Oxaprozin: An oxazole-propionic acid derivative, cyclooxygenase inhibitor, and non-steroidal anti-inflammatory drug that is used in the treatment of pain and inflammation associated with of OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; and ARTHRITIS, JUVENILE.
1,3-oxazoles;
monocarboxylic acid
analgesic;
non-steroidal anti-inflammatory drug
papaverinepapaverine : A benzylisoquinoline alkaloid that is isoquinoline substituted by methoxy groups at positions 6 and 7 and a 3,4-dimethoxybenzyl group at position 1. It has been isolated from Papaver somniferum.

Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.
benzylisoquinoline alkaloid;
dimethoxybenzene;
isoquinolines
antispasmodic drug;
vasodilator agent
primaquineprimaquine : An N-substituted diamine that is pentane-1,4-diamine substituted by a 6-methoxyquinolin-8-yl group at the N(4) position. It is a drug used in the treatment of malaria and Pneumocystis pneumonia.

Primaquine: An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances. (From Martindale, The Extra Pharmacopeia, 30th ed, p404)
aminoquinoline;
aromatic ether;
N-substituted diamine
antimalarial
flupirtineflupirtine: RN given refers to parent cpd without isomeric designationaminopyridine
duloxetineduloxetine
N-[7-(2-furanyl)-5-oxo-7,8-dihydro-6H-quinazolin-2-yl]acetamidequinazolines
pyrviniumpyrvinium : A quinolinium ion that is 1-methylquinolinium substituted by dimethylamino group at position 6 and a (E)-2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)ethenyl at position 2. It is a anthelminthic drug active against pinworms. The salts of pyrvinium can also be used as anticancer agents.

pyrvinium: RN given refers to parent cpd; synonyms vanquin & vankin refer to pamoate[2:1]; structure in Merck Index, 9th ed, #7810
quinolinium ionanthelminthic drug;
antineoplastic agent
2-(2-furanylmethyl)-3-[[2-(3-pyridinyl)-3H-benzimidazol-5-yl]amino]-3H-isoindol-1-oneisoindoles
gw2974GW2974: quinazoline derivative, which is able to block the activation of both the EGFR and erbB2pyridopyrimidine