15-hydroxyprostaglandin dehydrogenase (NAD+)
Class of enzymes
From Wikipedia, the free encyclopedia
Hydroxyprostaglandin dehydrogenase 15-(NAD) (the HUGO-approved symbol = HPGD; HGNC ID, HGNC:5154), also called 15-hydroxyprostaglandin dehydrogenase (NAD+), (EC 1.1.1.141), is an enzyme produced by the HPGD gene.
| hydroxyprostaglandin dehydrogenase 15-(NAD) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
15-hydroxyprostaglandin dehydrogenase dimer (NAD dependent), Human | |||||||||
| Identifiers | |||||||||
| EC no. | 1.1.1.141 | ||||||||
| CAS no. | 9030-87-9 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
Function
It catalyzes the NADâº-dependent oxidation of the 15-hydroxyl group of prostaglandins (primarily prostaglandin E2 or PGE2, but also others like PGD2 and PGF2α) and related eicosanoids (such as lipoxins), converting them to inactive 15-keto metabolites. This is the rate-limiting step in prostaglandin degradation, reducing their biological activity and regulating processes such as inflammation, cell proliferation, and tissue homeostasis.:[1][2]
Biological Role
- Downregulation in cancer â Can be reduced in tumors (e.g., colorectal, lung, breast), leading to elevated PGE2 levels that promote tumorigenesis; it acts as a tumor suppressor.[3]
- Aging and regeneration â Levels increase with age, contributing to tissue decline (e.g., muscle atrophy, cartilage loss). Inhibiting 15-PGDH elevates PGE2 and promotes regeneration in muscle, bone, cartilage, liver, colon, and hematopoietic tissues.[4][5]
- Inflammation and immunity â Degrades pro-inflammatory prostaglandins; inhibition can enhance resolution of inflammation or protect barriers like the blood-brain barrier in conditions such as Alzheimer's or traumatic brain injury.[6]
- Other roles â It is involved in wound healing, obesity-related inflammation, and pregnancy maintenance.
Therapeutic interest
Small-molecule inhibitors of 15-PGDH are under investigation for promoting tissue repair, countering sarcopenia, treating osteoarthritis, and supporting recovery after injury or transplantation. Mutations in HPGD can cause rare disorders like primary hypertrophic osteoarthropathy (digital clubbing, bone overgrowth).[7]
Ligands
Substrates
The two substrates of this enzyme are prostaglandin E2 and oxidised nicotinamide adenine dinucleotide (NAD+). Its products are 15-ketoprostaglandin E2, reduced NADH, and a proton.[15][16][17][18]
Class
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor.
The systematic name of this enzyme class is (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate:NAD+ 15-oxidoreductase. Other names in common use include NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (type I), PGDH, 11alpha,15-dihydroxy-9-oxoprost-13-enoate:NAD+ 15-oxidoreductase, 15-OH-PGDH, 15-hydroxyprostaglandin dehydrogenase, 15-hydroxyprostanoic dehydrogenase, NAD+-specific 15-hydroxyprostaglandin dehydrogenase, prostaglandin dehydrogenase, 15-hydroxyprostaglandin dehydrogenase (NAD+), and 15-PGDH.
