| Property | Summary |
|---|---|
| Gene name | **QDPR**; synonyms **DHPR**, **SDR33C1** (user-provided UniProt identity; pqac-00000023, pqac-00000025) |
| Protein name | **Dihydropteridine reductase**; also called **quinoid dihydropteridine reductase** / **DHPR** (pqac-00000003, pqac-00000041) |
| UniProt ID | **P09417** (user-provided target identity) |
| EC number | **EC 1.5.1.34** (user-provided target identity; pqac-00000003) |
| Molecular weight | Monomer ~**25–26 kDa**; native enzyme ~**50–52 kDa** (homodimer) (pqac-00000021, pqac-00000024) |
| Quaternary structure | **Homodimer**; dimer interface formed by a **four-helix bundle**; Rossmann-type dinucleotide fold in each protomer (pqac-00000019, pqac-00000020, pqac-00000021) |
| Cofactor | Primarily **NADH**; NADPH can support activity in some in vitro settings but is much less efficient, with strong NADH preference (~160-fold in a characterized homolog) (pqac-00000000, pqac-00000001, pqac-00000018) |
| Substrate | Physiologic substrate is **quinonoid dihydrobiopterin (qBH2)** / quinonoid dihydropteridines; enzyme tolerates several substituted quinonoid pteridines (pqac-00000003, pqac-00000007, pqac-00000042) |
| Product | **Tetrahydrobiopterin (BH4)** plus **NAD+** (pqac-00000003, pqac-00000041) |
| Reaction type | **NADH-dependent oxidoreductase** reaction in BH4 recycling: qBH2 + NADH + H+ → BH4 + NAD+; reaction proceeds by direct hydride transfer and is effectively irreversible under physiologic conditions (pqac-00000000, pqac-00000003, pqac-00000041) |
| Kinetic/mechanistic properties | **Ordered bi-bi** mechanism: NADH binds first, then qBH2; **pro-S hydride** transferred from the B-face of NADH to substrate N5; **free sulfhydryl groups** required; example kinetic constants from a well-characterized homolog: **Km(NADH) 23.1 ± 3.8 μM**, **Km(qDMPH2) 36.5 ± 7.1 μM** (pqac-00000000, pqac-00000001, pqac-00000018) |
| Tissue distribution | Widely distributed in animal tissues including **brain, adrenal medulla, heart, and lung**; functionally important in **CNS and liver**; recent work also identifies strong enrichment in **myelinating oligodendrocytes/myelin** (pqac-00000008, pqac-00000024, pqac-00000029) |
| Subcellular localization | Predominantly **cytosolic** enzyme in BH4 recycling; in CNS myelin studies, QDPR localizes to oligodendrocyte cell bodies and the **adaxonal non-compact compartment of myelin** (pqac-00000029, pqac-00000032) |
| Pathway | **Tetrahydrobiopterin (BH4) regeneration/recycling** pathway: after BH4 is oxidized during aromatic amino acid hydroxylation, **PCD/PCBD1** generates qBH2 and **QDPR** reduces qBH2 back to BH4; this sustains **PAH, TH, TPH**, and influences **NOS**-related BH4 homeostasis (pqac-00000011, pqac-00000014, pqac-00000015) |
| Primary biological function | Maintains intracellular **BH4 availability**, thereby supporting **phenylalanine hydroxylation**, **dopamine/serotonin biosynthesis**, and nitric-oxide-related biopterin balance (pqac-00000011, pqac-00000012, pqac-00000014) |
| Additional/putative functions | Literature suggests DHPR may help preserve **tetrahydrofolate** levels in brain where DHFR is low; secondary **ferric reductase** activity has been reported in nonhuman systems, but its physiologic importance in human QDPR remains unclear (pqac-00000036, pqac-00000040, pqac-00000039) |
| Disease associations | **Dihydropteridine reductase deficiency (DHPRD)** / BH4-deficient hyperphenylalaninemia: causes **hyperphenylalaninemia**, **dopamine and serotonin deficiency**, developmental delay, hypotonia, dystonia, seizures, microcephaly, and severe neurologic disease; DHPRD accounts for about **33% of HPA-associated BH4 deficiencies** in one consensus guideline (pqac-00000023, pqac-00000025, pqac-00000026) |
| Emerging disease links | Reduced or dysregulated QDPR/BH4 recycling has been linked to **tumor biology**: decreased QDPR expression in **colorectal cancer** is associated with a lower BH4:BH2 ratio and NOS uncoupling; QDPR loss has also been implicated in **pancreatic cancer immune suppression** in later literature summaries (pqac-00000028, pqac-00000027) |
| Chromosomal location | **Chromosome 4p15.3**; human gene spans **>20 kb** with **7 exons** and **732 bp coding sequence** (pqac-00000036) |


*Table: This table summarizes the core biochemical, structural, localization, pathway, and disease-related properties of human QDPR/dihydropteridine reductase. It is useful as a compact reference for functional annotation of UniProt P09417.*