Page last updated: 2024-10-24

regulation of hydrogen peroxide metabolic process

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving hydrogen peroxide. [PMID:14765119]

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that plays a dual role in biological systems. It can be both beneficial, acting as a signaling molecule involved in various cellular processes, and detrimental, causing oxidative stress and damage to cellular components. The regulation of H2O2 metabolism is crucial for maintaining cellular homeostasis and preventing oxidative damage. This regulation involves a complex interplay of enzymatic and non-enzymatic mechanisms.

Enzymatic regulation of H2O2 metabolism is primarily mediated by the following enzymes:

1. **Catalase:** This enzyme catalyzes the dismutation of H2O2 into water and oxygen. It is primarily located in peroxisomes, organelles responsible for the detoxification of H2O2. Catalase efficiently removes H2O2 at high concentrations, making it a crucial enzyme for H2O2 detoxification.

2. **Glutathione peroxidases (GPx):** GPx enzymes are a family of selenoproteins that catalyze the reduction of H2O2 to water using reduced glutathione (GSH) as a reducing agent. They are present in various cellular compartments and contribute to the removal of H2O2 at both high and low concentrations.

3. **Peroxiredoxins (Prx):** Prx enzymes are a family of thiol peroxidases that utilize reducing equivalents from thioredoxin (Trx) to reduce H2O2 to water. They are found in various cellular compartments and are important for controlling H2O2 signaling.

4. **Superoxide dismutases (SOD):** SOD enzymes catalyze the dismutation of superoxide radicals (O2-) into H2O2 and oxygen. While SODs do not directly remove H2O2, they play a role in regulating H2O2 levels by converting its precursor, superoxide.

5. **Other enzymes:** Other enzymes, such as NADPH oxidases (NOX) and cytochrome P450 monooxygenases, can contribute to H2O2 production during their normal metabolic activities.

Non-enzymatic regulation of H2O2 metabolism involves various mechanisms, including:

1. **Antioxidant molecules:** Molecules like glutathione (GSH), vitamin C (ascorbic acid), and vitamin E (α-tocopherol) can directly scavenge H2O2, reducing its concentration and oxidative potential.

2. **Protein thiol modifications:** H2O2 can react with cysteine residues in proteins, leading to the formation of sulfenic acid (SOH) modifications. These modifications can act as redox switches, regulating protein activity and cellular signaling pathways.

3. **Metal chelators:** Metals like iron and copper can catalyze the formation of H2O2 via the Fenton reaction. Metal chelators, such as transferrin and ferritin, bind to these metals and prevent their involvement in H2O2 production.

The regulation of H2O2 metabolism is a complex process involving multiple enzymatic and non-enzymatic mechanisms. It is essential for maintaining cellular homeostasis, preventing oxidative stress, and modulating signaling pathways involved in various cellular functions. Disruption of H2O2 homeostasis can contribute to the development of various diseases, including cancer, neurodegenerative disorders, and cardiovascular disease.'
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Proteins (1)

ProteinDefinitionTaxonomy
Ras-related C3 botulinum toxin substrate 1A Ras-related C3 botulinum toxin substrate 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P63000]Homo sapiens (human)

Compounds (16)

CompoundDefinitionClassesRoles
fasudilfasudil : 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
ketorolac5-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
perifosineammonium betaine;
phospholipid
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
ruboxistaurinruboxistaurin: 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
sotrastaurinsotrastaurin : 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-0973cobimetinib : 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
azd5438sulfonamide
nsc 23766NSC 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.
hydrochlorideantiviral agent;
apoptosis inducer;
EC 3.6.5.2 (small monomeric GTPase) inhibitor;
muscarinic antagonist
at13148
poziotinibHM781-36B: antitumor irreversible Pan-HER inhibitor for treatment of gastric canceracrylamides;
aromatic ether;
dichlorobenzene;
diether;
monofluorobenzenes;
N-acylpiperidine;
quinazolines;
secondary amino compound;
substituted aniline
antineoplastic agent;
apoptosis inducer;
epidermal growth factor receptor antagonist
bay 869766
gilteritinibgilteritinib : 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