Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
Metalloprotease
G-alpha
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Transporter
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
DNA
RNA
Compound
Inorganic ion
Predicted metabolite or user's structure
Reaction
Generic receptor
GPCR
Receptors with enzyme activity
Mitochondria
EPR
Golgi
Nucleus
Lysosome
Peroxisome
Cytoplasm
Extracellular

Normal process
Pathological process
Binding
Cleavage
Covalent modifications
Phosphorylation
Dephosphorylation
Transformation
Transport
Catalysis
Transcription regulation
MicroRNA binding
Competition
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Prostaglandin 2 biosynthesis and metabolism FM


Log In to Post A Comment

Prostaglandin 2 biosynthesis and metabolism FM

Prostaglandin 2 biosynthesis and metabolism FM

Prostaglandin biosynthesis starts with arachidonic acid that is oxidized toProstaglandin H2 ( PGH2 ) by Prostaglandin G/H synthase 1 precursor ( COX-1(PTGS1) ) or by Prostaglandin G/H synthase 2 precursor ( COX-2 (PTGS2) )[1], [2], [3], [4], [5]. Analternative reaction involves oxidation of arachidonic acid resulting in formationof Prostaglandin G2 ( PGG2 ) catalyzed either by COX-1 (PTGS1) [6], [7] and COX-2 (PTGS2) [8], [9], orby Epidermis-type lipoxygenase 3 ( LOXE3 ) [10], [11] andArachidonate 12-lipoxygenase, 12R type ( ALOX12B ) [10], [11]. COX-1 (PTGS1) and COX-2 (PTGS2) [9], [12], [13] can oxidize PGH2 directly to PGG2, whereasPGG2 can be reduced directly to PGH2 by a number of enzymes, e.g.,Peroxiredoxin-1 ( PRDX1 ), Peroxiredoxin-2 ( PRDX2 ), Thioredoxin-dependentperoxide reductase, mitochondrial precursor ( PRDX3 ), Peroxiredoxin-4 (PRDX4 ) [14], Peroxiredoxin-5, mitochondrial precursor ( PRDX5) [15], [16]). This reduction is coupled with the oxidation ofreduced glutathione.

PGH2 can be directly transformed to Prostaglandin E2 ( PGE2 ) by theProstaglandin E synthase ( PGES ) [17], [18] andProstaglandin E synthase 2 ( PGES2 ) [19], [20], [21], and to Prostaglandin D2 ( PGD2 ) by the Alcohol dehydrogenase [NADP+] (ALDX ) [22]. PGD2 can also be formed by Aldo-keto reductasefamily 1 member C3 ( AKR1C3 ) with 11-epi-PGF2alpha as a precursor [23], [24].

There are various ways to form Prostaglandin F2 alpha ( PGF2 alpha ). One wayis by reduction of the PGE2 catalyzed by Carbonyl reductase [NADPH] 1 (CBR1 ) [25], [26], Carbonyl reductase [NADPH] 2 (CBR2 ) [27], [28], Carbonyl reductase [NADPH] 3[29] and Dehydrogenase/reductase SDR family member 4 ( DHRS4 ) [30], [31]. PGF2 alpha can also be synthesized from PGD2in the reaction catalyzed by ALDX and AKR1C3 [32], [22]. Another way involves transformation of PGH2 also catalyzed byAKR1C3 [33]. PGE2 can also be reduced to 15-oxo-PGE2either by 15-hydroxyprostaglandin dehydrogenase [NAD+] ( HPGD ) [34],[35] or CBR1. The latter subsequently catalyzes the reduction of15-oxo-PGE2 to 15-ketoprostaglandin F2 alpha ( 15-Keto-PGF2alpha ) that isin turn reduced by CBR1 to PGF2 alpha.

PGE2 loses water moiety and transforms to Prostaglandin A2 ( PGA2 ). Thelatter is further transformed to Prostaglandin C2 ( PGC2 ). PGC2 can bealso transformed to Prostaglandin B2 ( PGB2 ) [36]. PGD2 can betransformed to Prostaglandin J2 ( PGJ2 ). Prostaglandin I2 (prostacyclin) synthase( PTGIS ) catalyzes dehydration on PGH2 resulting in the formation of Prostaglandin I2 ( PGI2 ) [37].

PGH2 is metabolized by a set of enzymes. Thromboxane A synthase 1 (platelet) (THAS ) forms 12-hydroxyheptadeca-5,8,10-trienoic acid and malonicdialdehyde as a byproduct, Thromboxane A(,2 ) [38], [39] and Thromboxane B2. Thromboxane A2 in its turn can spontaneouslyconvert to Thromboxane B2. Prostaglandin E synthase ( PGES) andProstaglandin E synthase 2 ( PGES2) catalyze the transformation of PGH2 to15-hydroperoxy-PGE1 [20], [18], [21].Cytochrome P450, family 4, subfamily F, polypeptide ( CYP4F12 ) reducesPGH2 to 20-hydroxy-prostaglandin H1 [40], [41].This enzyme also catalyzes the reduction of PGE2 to 9-oxo-PGF2alpha.PGE2 can be transformed to 5,6-dihydro-15-keto-prostaglandin E2 byHPGD [42], [43].

PGE2 metabolite 15-oxo-PGE2 is reduced to13,14-dihydro-15-keto-PGE2 by Prostaglandin reductase 1 ( LTB4DH ), whileanother metabolite 15-keto-PGF2alpha is also reduced by the same enzyme to13,14-dihydro-15-keto-PGF2alpha. The latter product is subsequently transformed byCBR1 to 13,14-dihydro-PGF2alpha. 15-Keto-PGF2 alpha can also beformed from PGF2 alpha via the reaction catalyzed by CBR1 [44]or HPGD [34], [45].

PGJ2 is metabolically transformed to 12-13,14-dihydro-PGJ2 delta.

THAS catalyzes the transformation of PGG2 to15-hydroperoxy-5,8,10-heptadecatrienoic acid with Malonic dialdehyde as abyproduct, or to 15-hydroperoxythromboxane B2. PGES and PGES2transform PGG2 to 15-hydroperoxy-PGE2 [18], [21].Prostaglandin D2 synthase (brain) ( PGHD ) and Prostaglandin D2 synthase 2hematopoietic ( PGDS ) can also catalyze formation of 15-hydroperoxy-PGD2[46], [47], [48]. PTGIS hydroxylatesPGG2 to 15-hydroperoxyprostacyclin.

PGI2 also undergoes significant metabolic transformation. It can be hydrolyzedto form 6-keto-prostaglandin F1alpha that is subsequently oxidized to6-keto-prostaglandin E1 [49]. Another pathway involves PGI2oxidation to 15-oxo-prostaglandin I2 [50] that is finally transformedby PTGIS to 15-oxo-prostaglandin H2.