Disease relevance of Qdpr

• Full-length rat dihydropteridine reductase (DHPR) cDNAs have been combined with a prokaryotic expression vector and introduced into Escherichia coli [1].
• Activities of cerebral dihydropteridine reductase and tyrosine hydroxylase in chronic uremia in rats [2].
• Individually, BH4, NADH and DHPR have no protection against H2O2 toxicity in PC 12 cells [3].
• Regulation of GTP cyclohydrolase I and dihydropteridine reductase in rat pheochromocytoma PC 12 cells [4].

Psychiatry related information on Qdpr

• The ability to inhibit spontaneous locomotor activity and to reduce levels of neurotransmitters and metabolites in the nigrostriatal system (striatum, substantia nigra) was compared with activity to inhibit dihydropteridine reductase (DHPR) in vitro [5].

High impact information on Qdpr

• This is of little value to dihydropteridine reductase but may be significant in the sequentially analogous short chain dehydrogenases/reductases, where a serine is the amino acid of choice for this position [6].
• Kinetic constants for the interaction of NADH and NADPH with native rat dihydropteridine reductase (DHPR) and an Escherichia coli expressed mutant (D-37-I) have been determined [7].
• Characterization and nucleotide binding properties of a mutant dihydropteridine reductase containing an aspartate 37-isoleucine replacement [7].
• The cleavage of reductively alkylated rat liver dihydropteridine reductase with cyanogen bromide afforded a mixture of peptides, six of which (CB-1 to CB-6) were isolated and purified by C8 reverse-phase high performance liquid chromatography [8].
• The pyridine dinucleotide-dependent dihydropteridine reductase from rat liver has been crystallized from various inorganic salts and from polyethylene glycol/ethanol mixtures using a vapor diffusion method [9].

Chemical compound and disease context of Qdpr

• In one instance, that of a threonine insertion, a mutant construct of the rat analog has been expressed in Escherichia coli and the DHPR isolated and characterised, confirming the marked changes this insert can create [10].

Biological context of Qdpr

• The results indicate that the DHPR cofactor binding site is similar to typical dinucleotide requiring dehydrogenases such as lactic acid and liver alcohol dehydrogenase [1].
• Because the 4-amino analogue of 6R-H4biopterin also inhibited dihydropteridine reductase (EC 1.6.99.7; IC50 20 microM), our results support the hypothesis that redox cycling of H4 biopterin might be required for the NO synthase reaction [11].
• Although hydroxylated derivatives of MPTP were reported to inhibit dihydropteridine reductase in vitro at lower concentrations than MPTP, 1-methyl-4-(p-hydroxyphenyl)-1,2,3,6-tetrahydropyridine showed only weak inhibition for tyrosine hydroxylation in striatal tissue slices [12].
• Dihydropteridine reductase and tyrosine hydroxylase activities in rat brain during development and senescence: a comparative study [13].

Anatomical context of Qdpr

• The results indicate that the nonmutant recombinant rat DHPR is an authentic replica of the natural protein and that the characteristics of DHPR activity are determined by a single gene product and do not require specific modification via the eukaryotic cell [1].
• Biochemical changes caused by the infusion into the substantia nigra of the rat of MPTP and related compounds which antagonise dihydropteridine reductase [5].
• A fourth gene, quinoid dihydropteridine reductase was expressed at lower levels in white matter of the adolescent forebrain compared with the adult, but was not affected by nicotine [14].
• Therefore, there would not appear to be any correlation between the ability to modify dopamine neuronal function, as assessed behaviourally or biochemically, and ability to inhibit DHPR in synaptosomes from the striatum of the rat in vitro [5].
• The estimation of dihydropteridine reductase in human blood cells [15].

Associations of Qdpr with chemical compounds

• Cyanogen bromide cleavage of reductively alkylated homogeneous rat liver dihydropteridine reductase afforded several peptide fragments identifiable by polyacrylamide electrophoresis of which 6 (CB-1 to CB-6) could be individually isolated by C8 reverse phase HPLC [16].
• The interactions of a homogeneous preparation of rat liver dihydropteridine reductase with NADH, NADPH, NAD+, NADP+, and the 1-N6-ethenoadenine derivative of NAD+ have been investigated by fluorescence titration, circular dichroism, equilibrium dialysis, Sephadex G-25 chromatography, and polyacrylamide gel electrophoresis [17].
• Pyridine nucleotide interaction with rat liver dihydropteridine reductase [17].
• In addition to the pyrimidine having activity with phenylalanine hydroxylase, a product of the pyrimidine is also a substrate for dihydropteridine reductase [18].
• Contrasting effects of N5-substituted tetrahydrobiopterin derivatives on phenylalanine hydroxylase, dihydropteridine reductase and nitric oxide synthase [19].

Other interactions of Qdpr

• Chronic (3 months) lead exposure increased the quinonoid dihydropteridine reductase activity and the tetrahydrobiopterin content but did not affect the GTP-cyclohydrolase activity and the dihydrobiopterin content [20].
• A conformational stability-dependent variable degree of stoichiometric coupling between quinonoid dihydropteridine reductase and tyrosine hydroxylase is proposed as a short-latency influence on hydroxylase cofactor levels [21].

Analytical, diagnostic and therapeutic context of Qdpr

• Positive clones were isolated, and detailed examination of five of these by restriction endonucleases and dideoxy sequence analyses allowed identification of the entire coding region for dihydropteridine reductase [8].
• An enzyme immunoassay for the quantitation of dihydropteridine reductase [22].
• DPR was purified by subsequent chromatographies with Sephadex G-50 and blue Sepharose to a purity of 50% [23].
• Purified rat-liver dihydropteridine reductase is homogeneous by gel filtration (Mr approximately 51,000), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Mr approximately 25,500), and native polyacrylamide gel electrophoresis, suggesting that the enzyme is composed of two identical subunits [24].
• A competitive, enzyme-linked immunosorbent assay for the quantitative determination of dihydropteridine reductase (DHPR) is described [22].

References