Page last updated: 2024-10-24

platelet activating factor metabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways involving platelet activating factor, 1-O-alkyl-2-acetyl-sn-glycerol 3-phosphocholine, where alkyl = hexadecyl or octadecyl. Platelet activating factor is an inflammatory mediator released from a variety of cells in response to various stimuli. [ISBN:0198547684]

Platelet-activating factor (PAF) is a potent phospholipid mediator involved in a wide range of biological processes, including inflammation, allergy, and thrombosis. Its metabolic process is complex and involves several key enzymes and pathways.

1. **Synthesis:** PAF is synthesized from membrane phospholipids, primarily phosphatidylcholine, by the action of phospholipase A2 (PLA2) and acetyltransferase enzymes. PLA2 hydrolyzes phosphatidylcholine to lysophosphatidylcholine, which is then acetylated by acetyltransferase to produce PAF.

2. **Activation:** PAF exerts its effects by binding to a specific G protein-coupled receptor (PAF receptor) present on various cell types, including platelets, neutrophils, endothelial cells, and smooth muscle cells.

3. **Signal Transduction:** Upon binding to its receptor, PAF activates downstream signaling pathways, including the phospholipase C (PLC) pathway, the protein kinase C (PKC) pathway, and the mitogen-activated protein kinase (MAPK) pathway.

4. **Biological Effects:** Activation of these signaling pathways leads to a cascade of cellular responses, including:

* **Platelet aggregation:** PAF is a potent platelet activator, inducing aggregation and release of granules containing various mediators, such as serotonin and thromboxane A2.

* **Inflammation:** PAF contributes to inflammatory responses by promoting the recruitment and activation of leukocytes, such as neutrophils, macrophages, and eosinophils. It also increases vascular permeability and stimulates the production of pro-inflammatory cytokines.

* **Bronchoconstriction:** PAF induces bronchoconstriction by stimulating smooth muscle contraction in the airways.

* **Hypersensitivity Reactions:** PAF plays a role in allergic reactions, such as anaphylaxis, by promoting mast cell degranulation and the release of histamine.

5. **Inactivation:** PAF is rapidly inactivated by a specific enzyme called PAF acetylhydrolase (PAF-AH). PAF-AH hydrolyzes the acetyl group from PAF, converting it to lysophosphatidylcholine, which is inactive.

In summary, the PAF metabolic process involves the synthesis, activation, signal transduction, and inactivation of this potent lipid mediator. It plays a crucial role in diverse biological processes, including inflammation, allergy, and thrombosis. Its intricate regulation is essential for maintaining cellular homeostasis and preventing excessive inflammatory responses.'
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Proteins (2)

ProteinDefinitionTaxonomy
Platelet-activating factor acetylhydrolaseA platelet-activating factor acetylhydrolase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13093]Homo sapiens (human)
85/88 kDa calcium-independent phospholipase A2An 85/88 kDa calcium-independent phospholipase A2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O60733]Homo sapiens (human)

Compounds (20)

CompoundDefinitionClassesRoles
ly 171883LY 171883: structure in first source; leukotriene receptor antagonist

tomelukast : A member of the class of acetophenones that is 1-phenylethanone substituted at position 2 by a hydroxy group, a propyl group at position 3 and a 4-(1H-tetrazol-5-yl)butoxy group at position 4. A leukotriene antagonist, it exhibits anti-asthmatic activity.
acetophenones;
aromatic ether;
phenols;
tetrazoles
anti-asthmatic drug;
leukotriene antagonist
vitamin k 3Vitamin K 3: A synthetic naphthoquinone without the isoprenoid side chain and biological activity, but can be converted to active vitamin K2, menaquinone, after alkylation in vivo.1,4-naphthoquinones;
vitamin K
angiogenesis inhibitor;
antineoplastic agent;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
human urinary metabolite;
nutraceutical
raloxifeneraloxifene : A member of the class of 1-benzothiophenes that is 1-benzothiophene in which the hydrogens at positions 2, 3, and 6 have been replaced by p-hydroxyphenyl, p-[2-(piperidin-1-yl)ethoxy]benzoyl, and hydroxy groups, respectively.1-benzothiophenes;
aromatic ketone;
N-oxyethylpiperidine;
phenols
bone density conservation agent;
estrogen antagonist;
estrogen receptor modulator
1,6-bis(cyclohexyloximinocarbonyl)hexane1,6-bis(cyclohexyloximinocarbonyl)hexane: selective inhibitor of canine platelet diglyceride lipasecarbamate ester;
organonitrogen compound
vorinostatvorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL).

Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.
dicarboxylic acid diamide;
hydroxamic acid
antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
5,5-dimethylhydantoin5,5-dimethylhydantoin: RN given refers to parent cpdimidazolidine-2,4-dione
benzenesulfonamidesulfonamide
plumbaginplumbagin : A hydroxy-1,4-naphthoquinone that is 1,4-naphthoquinone in which the hydrogens at positions 2 and 5 are substituted by methyl and hydroxy groups, respectively.

plumbagin: a superoxide anion generator
hydroxy-1,4-naphthoquinone;
phenols
anticoagulant;
antineoplastic agent;
immunological adjuvant;
metabolite
wy 48252Wy 48252: leukotriene D4 antagonist
4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenolstilbenoid
spiroglumidespiroglumide: a CCK receptor antagonist; antigastrin; structure given in first source
3-octylthio-1,1,1-trifluoro-2-propanone3-octylthio-1,1,1-trifluoro-2-propanone: a pesticide synergist; inhibits juvenile hormone esterase
varespladibaromatic ether;
benzenes;
dicarboxylic acid monoamide;
indoles;
monocarboxylic acid;
primary carboxamide
anti-inflammatory drug;
antidote;
EC 3.1.1.4 (phospholipase A2) inhibitor
tamoxifenstilbenoid;
tertiary amino compound
angiogenesis inhibitor;
antineoplastic agent;
bone density conservation agent;
EC 1.2.3.1 (aldehyde oxidase) inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
estrogen antagonist;
estrogen receptor antagonist;
estrogen receptor modulator
orlistatorlistat : A carboxylic ester resulting from the formal condensation of the carboxy group of N-formyl-L-leucine with the hydroxy group of (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]oxetan-2-one. A pancreatic lipase inhibitor, it is used as an anti-obesity drug.

Orlistat: A lactone derivative of LEUCINE that acts as a pancreatic lipase inhibitor to limit the absorption of dietary fat; it is used in the management of obesity.
beta-lactone;
carboxylic ester;
formamides;
L-leucine derivative
anti-obesity agent;
bacterial metabolite;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
EC 3.1.1.3 (triacylglycerol lipase) inhibitor
arachidonyltrifluoromethaneAACOCF3 : A fatty acid derivative that is arachidonic acid in which the OH part of the carboxy group has been replaced by a trifluoromethyl group

arachidonyltrifluoromethane: structure given in first source; inhibits 85-kDa phospholipase A2
fatty acid derivative;
ketone;
olefinic compound;
organofluorine compound
EC 3.1.1.4 (phospholipase A2) inhibitor
manoalidemanoalide : A sesterterpenoid isolated from the marine sponge Luffariella variabilis and which has been shown to exhibit inhibitory activity towards phospholipase A2.

manoalide: phospholipase A2 inhibitor; sesterterpene from marine sponge L. variabilis; structure given in first source
butenolide;
lactol;
sesterterpenoid
EC 3.1.1.4 (phospholipase A2) inhibitor;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
metabolite
darapladibdarapladib: a selective lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) inhibitor, on biomarkers of cardiovascular (CV) risk
sb-435495SB-435495: structure in first source
14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene: has antineoplastic activity; also inhibits Fms-like tyrosine kinase-3; structure in first source