regulation of respiratory burst
Definition
Target type: biologicalprocess
Any process that modulates the rate frequency or extent of a phase of elevated metabolic activity, during which oxygen consumption increases; this leads to the production, by an NADH dependent system, of hydrogen peroxide (H2O2), superoxide anions and hydroxyl radicals. [GOC:dph, GOC:tb]
The respiratory burst, a rapid increase in oxygen consumption and the production of reactive oxygen species (ROS) by phagocytic cells, is a crucial component of the innate immune response. This process is tightly regulated to ensure effective pathogen elimination while minimizing damage to host tissues. The key players in this regulatory dance are:
1. **Signal Recognition and Activation:** Phagocytes, such as neutrophils and macrophages, recognize pathogens through pattern recognition receptors (PRRs) on their surface. These receptors bind to pathogen-associated molecular patterns (PAMPs), triggering a cascade of signaling events.
2. **Activation of NADPH Oxidase:** The primary enzyme responsible for ROS production is NADPH oxidase. Upon activation, this enzyme assembles in the plasma membrane, forming a complex that catalyzes the transfer of electrons from NADPH to molecular oxygen, generating superoxide anion (O2-).
3. **Regulation of NADPH Oxidase Activity:** The assembly and activation of NADPH oxidase are tightly controlled. Several key proteins play regulatory roles, including:
* **p47phox and p67phox:** These cytosolic proteins translocate to the membrane upon activation and bind to the membrane-bound subunits (gp91phox and p22phox), facilitating the assembly of the NADPH oxidase complex.
* **Rac2:** This small GTPase acts as a molecular switch, promoting the translocation of cytosolic components to the membrane and activating NADPH oxidase.
* **Protein Kinases:** Various kinases, including protein kinase C (PKC), MAP kinases, and PI3 kinase, phosphorylate key components of the NADPH oxidase complex, further enhancing its activity.
4. **ROS Generation and Antioxidant Defense:** The superoxide anion (O2-) generated by NADPH oxidase is highly reactive and can directly damage pathogens. However, it is also converted into other ROS, including hydrogen peroxide (H2O2), hydroxyl radical (OH-), and hypochlorous acid (HOCl), via enzymatic reactions catalyzed by superoxide dismutase (SOD), myeloperoxidase (MPO), and catalase. These ROS contribute to pathogen killing and inflammation.
5. **Termination of Respiratory Burst:** The respiratory burst is a transient process. Once the threat is eliminated, the signal transduction pathways are deactivated, and the NADPH oxidase complex disassembles. Antioxidant enzymes, such as SOD, catalase, and glutathione peroxidase, neutralize excess ROS, minimizing damage to host cells.
The regulation of the respiratory burst is a complex process involving multiple signaling pathways and enzymatic activities. The fine-tuning of these mechanisms ensures that the production of ROS is sufficient to eliminate pathogens while protecting host cells from oxidative stress. This intricate dance of activation and inactivation is essential for maintaining immune homeostasis.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Ras-related C3 botulinum toxin substrate 1 | A Ras-related C3 botulinum toxin substrate 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P63000] | Homo sapiens (human) |
Compounds (16)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| fasudil | fasudil : An isoquinoline substituted by a (1,4-diazepan-1-yl)sulfonyl group at position 5. It is a Rho-kinase inhibitor and its hydrochloride hydrate form is approved for the treatment of cerebral vasospasm and cerebral ischemia. fasudil: intracellular calcium antagonist; structure in first source | isoquinolines; N-sulfonyldiazepane | antihypertensive agent; calcium channel blocker; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; geroprotector; neuroprotective agent; nootropic agent; vasodilator agent |
| ketorolac | 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid : A member of the class of pyrrolizines that is 2,3-dihydro-1H-pyrrolizine which is substituted at positions 1 and 5 by carboxy and benzoyl groups, respectively. ketorolac : A racemate comprising equimolar amounts of (R)-(+)- and (S)-(-)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid. While only the (S)-(-) enantiomer is a COX1 and COX2 inhibitor, the (R)-(+) enantiomer exhibits potent analgesic activity. A non-steroidal anti-inflammatory drug, ketorolac is mainly used (generally as the tromethamine salt) for its potent analgesic properties in the short-term management of post-operative pain, and in eye drops to relieve the ocular itching associated with seasonal allergic conjunctivitis. It was withdrawn from the market in many countries in 1993 following association with haemorrhage and renal failure. Ketorolac: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed) | amino acid; aromatic ketone; monocarboxylic acid; pyrrolizines; racemate | analgesic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; non-steroidal anti-inflammatory drug |
| sanguinarine chloride | |||
| chelerythrine chloride | |||
| perifosine | ammonium betaine; phospholipid | EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor | |
| ruboxistaurin | ruboxistaurin: inhibits protein kinase C beta; structure in first source | ||
| s 1033 | (trifluoromethyl)benzenes; imidazoles; pyridines; pyrimidines; secondary amino compound; secondary carboxamide | anticoronaviral agent; antineoplastic agent; tyrosine kinase inhibitor | |
| sotrastaurin | sotrastaurin : A member of the class of maleimides that is maleimide which is substituted at position 3 by an indol-3-yl group and at position 4 by a quinazolin-4-yl group, which in turn is substituted at position 2 by a 4-methylpiperazin-1-yl group. It is a potent and selective inhibitor of protein kinase C and has been investigated as an immunosuppresant in renal transplant patients. sotrastaurin: a potent protein kinase C-selective inhibitor; structure in first source | indoles; maleimides; N-alkylpiperazine; N-arylpiperazine; quinazolines | anticoronaviral agent; EC 2.7.11.13 (protein kinase C) inhibitor; immunosuppressive agent |
| gdc-0973 | cobimetinib : A member of the class of N-acylazetidines obtained by selective formal condensation of the carboxy group of 3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoic acid with the secondary amino group from the azetidine ring of 3-[(2S)-piperidin-2-yl]azetidin-3-ol. An inhibitor of mitogen-activated protein kinase that is used (as its fumarate salt) in combination with vemurafenib for the treatment of patients with unresectable or metastatic melanoma. cobimetinib: has antineoplastic activity; structure in first source | aromatic amine; difluorobenzene; N-acylazetidine; organoiodine compound; piperidines; secondary amino compound; tertiary alcohol | antineoplastic agent; EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor |
| azd5438 | sulfonamide | ||
| nsc 23766 | NSC 23766 trihydrochloride : A hydrochloride resulting from the formal reaction of NSC 23766 with 3 mol eq. of hydrogen chloride. An inhibitor of the signalling G-protein known as RAC1 (Ras-related C3 botulinum toxin substrate 1). Rac1 inhibitor : Any inhibitor of Rac1. | hydrochloride | antiviral agent; apoptosis inducer; EC 3.6.5.2 (small monomeric GTPase) inhibitor; muscarinic antagonist |
| at13148 | |||
| poziotinib | HM781-36B: antitumor irreversible Pan-HER inhibitor for treatment of gastric cancer | acrylamides; aromatic ether; dichlorobenzene; diether; monofluorobenzenes; N-acylpiperidine; quinazolines; secondary amino compound; substituted aniline | antineoplastic agent; apoptosis inducer; epidermal growth factor receptor antagonist |
| bay 869766 | |||
| gilteritinib | gilteritinib : A member of the class of pyrazines that is pyrazine-2-carboxamide which is substituted by {3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}nitrilo, (oxan-4-yl)nitrilo and ethyl groups at positions 3,5 and 6, respectively. It is a potent inhibitor of FLT3 and AXL tyrosine kinase receptors (IC50 = 0.29 nM and 0.73 nM, respectively). Approved by the FDA for the treatment of acute myeloid leukemia in patients who have a FLT3 gene mutation. gilteritinib: an FLT3/AXL protein tyrosine kinase inhibitor | aromatic amine; monomethoxybenzene; N-methylpiperazine; oxanes; piperidines; primary carboxamide; pyrazines; secondary amino compound | antineoplastic agent; apoptosis inducer; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor |
| glpg0634 |