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At least 19 recordsLinked to original sources
PubMed1992

Tetrahydro-6-biopterin is associated with tetrahydro-7-biopterin in primary murine mast cells.

Murine bone marrow-derived mast cells proliferate in response to interleukin 3. In addition to 6-biopterin, 7-biopterin was identified in these cells by HPLC analysis of iodine oxidized extracts and by alkaline permanganate oxidation to the 6- and 7-carboxylic acids. 7-Biopterin comprised 31.9 (+/- 7.7)% of the total biopterin. It was absent in cells which were grown with of L-p-chlorophenylalanine, an inhibitor of tryptophan 5-mono-oxygenase. Both 6- and 7-biopterin were present in the cell as their tetrahydro forms. From these data we conclude that 7-biopterin, in contrast to e.g. brain tissue, regularly occurs as a normal metabolite in primary mast cells and that it is generated during hydroxylation of tryptophan.

Animals↗
PubMed1984

Biopterin cofactor biosynthesis: GTP cyclohydrolase, neopterin and biopterin in tissues and body fluids of mammalian species.

Levels of GTP cyclohydrolase, neopterin and biopterin were determined in tissues and body fluids of humans, monkey, dog and mouse. Highest levels of GTP cyclohydrolase and biopterin were found in pineal, liver, spleen, bone marrow, whole adrenal gland and small intestine. High levels of biopterin were found in the urine of all species examined. High levels of neopterin were found only in the urine of humans and monkeys, very low levels could be detected in dog, while none could be detected in mouse, rat, guinea pig or hamster urine.

Aminohydrolases↗
PubMed1995

Simultaneous determination of N2-(3-aminopropyl)biopterin (oncopterin), biopterin and neopterin by high-performance liquid chromatography with fluorescence detection.

A high-performance liquid chromatographic method is described for the simultaneous determination of N2-(3-aminopropyl)biopterin (oncopterin, a newly found natural pteridine in urine from cancer patients), biopterin, and neopterin in urine. For the detection and quantification of the compounds, fluorometry was used. Using Develosil ODS K-5 and Develosil ODS HG-5 reversed-phase columns and a Nucleosil 100-SSA strong cation-exchange column, oncopterin, biopterin, and neopterin in urine were completely separated and assayed simultaneously by fluorescence detection. Similar values of oncopterin were obtained using each of the three columns, and the Develosil ODS K-5 reversed-phase column gave the most satisfactory separation. The sensitivity was high enough to measure 1 pmol of each pteridine. The HPLC method was highly reproducible. Our preliminary results indicate that oncopterin could be a most sensitive marker for cancer.

Biomarkers, Tumor↗
PubMed1981

Biopterin. VII. Inhibition of synthesis of reduced biopterins and its bearing on the function of cerebral tryptophan-5-hydroxylase in vivo.

Repeated intraventricular injections of 2,4-diamino-6-hydroxypyrimidine (DAO-Pyr), inhibitor of D-erythro-q-dihydroneopterin triphosphate synthetase, inhibited q-BH2 synthesis from GTP, markedly increased accumulation of 2-amino-4-hydroxy-5 (or -6)-formamido-6-triphosphoribosylaminopyrimidine (FPyd-P3) and brought about a 60% decrease in the in vivo of reduced biopterin (BH2 and BH4) pool in the brain. Nevertheless, there was no effect on the rate of hydroxylation of L-tryptophan or on the 5-hydroxytryptamine level in rat brain. These data emphasized the significance of the rate of hydrogen transfer and the limitation of the concept of "unsaturation" (i.e., the absolute amount of the carrier pterin molecule) for the synthesis of neurotransmitters in vivo.

Animals↗
PubMed1989

Interleukin-2 enhances biopterins and catecholamines production during adoptive immunotherapy for various cancers.

Biopterins production during three different protocols for adoptive immunotherapy for human cancer was investigated. Adoptive immunotherapy treatment with interleukin-2 (IL-2) was carried out for 13 patients with malignant melanoma; eight with metastatic renal cell carcinoma; and three with metastatic colon cancer. The authors estimated total biopterins in plasma and lymphokine (IL-2)-activated killer cells (LAK) from these patients before and during various treatment phases to determine if increased biopterins production reflects leukocyte activation by IL-2 or antitumor activity. They noted an increased synthesis of total "biopterins," i.e., biopterin; 7,8-dehydrobiopterin; and L-neopterin in LAK cells and plasma which correlated with IL-2 exposure. Mean plasma biopterins were normal (1.2 +/- 0.5 ng/ml) before therapy; in contrast, biopterins increased significantly to 3.4 +/- 1.9 ng/ml and 3.9 +/- 1.9 ng/ml during IL-2 and IL-2 + LAK treatment each, respectively. Similar biopterin elevations were noted irrespective of the different adoptive immunotherapy protocols used. Elevated biopterins decreased to normal levels (1.2 +/- 0.7 ng/ml) when IL-2 treatment was omitted. Tumor regression with adoptive immunotherapy did not correlate with increased plasma biopterins. Increased biopterins production was also associated with increase in plasma catecholamine after IL-2 treatment during adoptive immunotherapy. Conceivably increased biopterins, induced by IL-2 activation of a leukocyte population, is a cell-mediated consequence not necessarily serving as a signal for the antitumor effect associated with adoptive immunotherapy.

Adult↗
PubMed1986

Neurological aspects of biopterin metabolism.

Plasma total biopterin concentration was measured by bioassay in 59 infants with hyperphenylalaninaemia and in 50 children with developmental regression and or movement disorder with normal plasma phenylalanine concentrations. In infants with raised phenylalanine concentrations plasma biopterin concentrations were significantly raised in proportion to the phenylalanine values. Five patients had plasma biopterin concentrations at the extremes of the range, and of these two had defective biopterin metabolism. One with low plasma biopterin concentration apparently had a partial defect of biopterin synthesis but died before investigations were complete. One with high plasma biopterin concentration, even when phenylalanine concentrations had fallen to the normal range, had dihydropteridine reductase deficiency. In this patient concentrations of homovanillic acid and 5-hydroxyindolacetic acid in the cerebrospinal fluid (CSF) were severely reduced. In children without hyperphenylalaninaemia plasma biopterin concentrations were normal. Twenty two patients were subjected to lumbar puncture, of whom six with developmental regression without movement disorder had normal CSF biopterin concentrations, and 11 with movement disorder other than torsion dystonia had significantly lower CSF biopterin concentrations. Five patients with torsion dystonia had normal biopterin concentrations.

Adolescent↗
PubMed2002

Plasma biopterin levels and depressive state in pregnancy and the early puerperal period.

Plasma total biopterin and tetrahydrobiopterin levels of 14 normal pregnant and 15 normal puerperal women (within 1 week after delivery) were measured. In the first group, total biopterin levels were already increased (average: 18.2 pmol/ml) in the second trimester and remained high until the early puerperal period. In the second trimester, the ratio of tetrahydrobiopterin to total biopterin levels decreased to 72.3% and even further to 66.1% in the third trimester. This tendency continued until the puerperal period. Compared with the control group (12 healthy nonpregnant women), total biopterin levels increased during pregnancy and the puerperal period (p < 0.001), and the ratio in the third trimester and the early puerperal period decreased (p < 0.001). The depressive state according to Zung's score appeared most markedly in the third trimester with a mean score of 48, and tended to recover to a mean score of 36.2 in the early puerperal period. In this period, a correlation was found between Zung's score and the total biopterin levels (r = 0.80), and the ratio of tetrahydrobiopterin levels to the total biopterin levels (r = -0.92). In the early puerperal period, total biopterin levels were higher in subjects with Zung's scores > or = 36 (p < 0.001); the ratios of this group were lower than those of subjects with Zung's scores <36 (p < 0.001). Plasma biopterin levels in pregnancy and the early puerperal period closely resembled those of patients with mood disorders who show depressive symptoms from a psychoneurological perspective. Therefore, it seems possible that a depressive state in pregnancy and the early puerperal period has the same pathology as depression.

Adult↗
PubMed1988

Dystonia with marked diurnal variation associated with biopterin deficiency.

Two pairs of siblings with severe dystonia with marked diurnal fluctuation had both reduced CSF concentration of biopterin and marked symptomatic improvement of the dystonia in response to levodopa. Whether the reduced concentration of biopterin reflects focal abiotrophy of biopterin-containing neurons or deficiency of biopterin synthesis is uncertain. A fifth individual, who had a systemic deficiency of biopterin synthesis, shared the features of reduced biopterin in CSF, marked diurnal variation in the degree of dystonia, and clinical improvement in response to levodopa. Generalized dystonia with marked diurnal fluctuation was therefore shared by the four patients in whom biopterin deficiency was limited to the CNS and the patient with systemic deficiency of biopterin.

Adolescent↗
PubMed1982

Biopterin level in peripheral blood cells as a marker for hemopoietic cell proliferation during leukemia and polycythemia vera.

Using the Crithidia assay 3.0 ng biopterin/ml blood was found, of which one third was present in the plasma. The erythrocyte fraction comprised 1.7 ng and the buffy coat 0.33 ng. After Ficoll separation 0.050 ng were found in the lymphocyte layer of 1 ml blood. During blast crisis of chronic myelocytic leukemias increased amounts of biopterin were found in the erythrocyte fraction and in the buffy coat. The high biopterin concentration per unit of protein in the white cell fraction indicated the presence of blasts. In Polycythemia vera increased amounts of biopterin in both the red cell fraction and in the buffy coat were also found but the percentage distribution within total cellular biopterin was markedly shifted toward the erythrocyte fraction. In cases of chronic and acute lymphocytic leukemias the low amounts of biopterin in the red cell fraction agreed with the current view of partial extinction of the erythropoietic line. The isolated lymphoblasts were characterized by high biopterin concentrations per unit of protein. During remission the biopterin patterns approached normal levels.

Biopterins↗
PubMed1989

Inhibition of biopterin synthesis and DOPA production in PC-12 pheochromocytoma cells induced by 6-aminonicotinamide.

Pheochromocytoma cells (clone PC-12) were treated with 6-aminonicotinamide. Tetrahydrobiopterin content and DOPA production of the cells were determined by reverse-phase HPLC and subsequent electrochemical detection. The same chromatographic system was used to determine total biopterin (tetrahydrobiopterin, dihydrobiopterin and quinoide dihydrobiopterin) by fluorescence detection. Tetrahydrobiopterin plays a decisive role as cofactor of tyrosine hydroxylase for the biosynthesis of DOPA and dopamine. Addition of 6-aminonicotinamide to the culture medium resulted in the accumulation of 6-phosphogluconate, suggesting that PC-12 cells synthesize 6-aminonicotinamide-adenine-dinucleotide-phosphate (6-ANADP) by a glycohydrolase localized in the endoplasmic reticulum. This substance is known to be a strong inhibitor of 6-phosphogluconate dehydrogenase and leads to a blockade of the pentose phosphate pathway. In our experiments, the synthesis of biopterins was depressed after application of 6-aminonicotinamide. The decrease of intracellular tetrahydrobiopterin and total biopterin by 6-aminonicotinamide at different concentrations was strongly correlated with a reduced cellular DOPA production. The decreased content of biopterin cofactor was compensated by addition of the precursor sepiapterin, indicating that the NADPH2-dependent reductases in biopterin synthesis are not inhibited by the antimetabolite. However, DOPA production remained suppressed at the same time. After application of NADH2, we observed an increased DOPA production though the decreased biopterin levels remained almost unchanged. The results imply that the first step in the synthesis of biopterin from GTP as well as the recycling pathways of the oxidized cofactor might be the site of action of the antimetabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Aminonicotinamide↗
PubMed2006

Analysis of plasma biopterin levels in psychiatric disorders suggests a common BH4 deficit in schizophrenia and schizoaffective disorder.

Tetrahydrobiopterin (BH4) is an essential cofactor for amine neurotransmitter synthesis. BH4 also stimulates and modulates the glutamatergic system, and regulates the synthesis of nitric oxide by nitric oxide synthases. A connection between BH4 deficiencies and psychiatric disorders has been previously reported; major depression and obsessive-compulsive disorder have been found in subjects with a BH4 deficiency disorder and more recently we have observed a robust plasma deficit of biopterin (a measure of BH4), in a large group of schizophrenic patients compared to control subjects. To extend our previous finding in schizophrenia, we analyzed plasma biopterin levels from patients with schizoaffective and bipolar disorders. A significant difference in biopterin was seen among the diagnostic groups (P < 0.0001). Post hoc analyses indicated significant biopterin deficits relative to the normal control group for the schizoaffective group, who had biopterin levels comparable to the schizophrenic group. Bipolar disorder subjects had plasma biopterin levels that were higher that the schizoaffective disorder group and significantly higher than the schizophrenic group. The demonstrated significant biopterin deficit in both schizophrenia and schizoaffective disorder, may suggest an etiological role of a BH4 deficit in these two disorders, via dysregulation of neurotransmitter systems.

Adult↗
PubMed1986

Biopterin and neurotransmitter amine metabolism in children with acute lymphoblastic leukemia receiving methotrexate therapy.

To test the hypothesis that some of the neurologic sequelae of treatment for acute lymphoblastic leukemia (ALL) might be related to abnormalities in biopterin metabolism associated with methotrexate (MTX) therapy, total biopterin levels in cerebrospinal fluid (CSF) and plasma, and homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) were measured in a cross-sectional study of 80 children with ALL. For comparison, biopterins were also measured in a group of children of similar age undergoing investigation for neurologic disease. In children with ALL studied before therapy, no significant difference was found between the means of plasma biopterin or CSF biopterin concentrations and the means in the control group. In children receiving MTX, plasma biopterin values were higher in the group given maintenance therapy than in children observed before treatment. CSF levels were significantly increased only in those patients who had completed 2 years of maintenance therapy. CSF concentrations of HVA and 5HIAA in patients with ALL who had received no treatment (median values 52 and 18 ng/ml, respectively) showed a wide scatter and were inversely related to age. In patients receiving MTX, concentrations of these metabolites were higher than in the untreated group, again reaching a peak in patients just completing 2 years of treatment (median HVA 110 ng/ml, 5HIAA 34 ng/ml). These results provide no support for the idea that neurotransmitter amine deficiency occurs in children with ALL receiving MTX, and indicate, rather, that amine and biopterin synthesis increases in such patients.

Adolescent↗
PubMed1981

Biosynthesis of biopterin: adrenergic cyclic adenosine monophosphate-dependent inhibition in the pineal gland.

Pineal glands in organ culture synthesize and release biopterin and are able to maintain concentrations of biopterin occurring in vivo for up to 54 hours in vitro. The intracellular biopterin content is reduced 50 percent by treatment with l-norepinephrine or cyclic adenosine monophosphate derivatives, but not by d-norepinephrine. This is an indication that biopterin levels are regulated by an adrenergic cyclic adenosine monophosphate-dependent mechanism. The decline in tissue biopterin content, produced mainly by inhibited of biosynthesis, is maximal at 6 hours and is not associated with either an increase in biopterin release or a shift in the reduction state of the biopterin.

1-Methyl-3-isobutylxanthine↗
PubMed1999

[Biopterin synthesis and GTP cyclohydrolase I mRNA expression in rats following endotoxic shock].

OBJECTIVE: To investigate the potential role of changes in biopterin (tetrahydrobiopterin and more oxidized species) synthesis and GTP cyclohydrolase I (GTP-CHI) mRNA expression in endotoxic shock. METHODS: SD rats were subjected to endotoxic shock by a bolus injection of lipopolysaccharide (15 mg/kg, i.p.), biopterin and GTP-CHI mRNA levels in liver, kidney, and intestine were determined at 4, 8 hours following endotoxin challenge. RESULTS: Tissue biopterin levels significantly elevated in liver, kidney, and intestine, with high levels sustaining for 8 hours after endotoxin challenge (P < 0.05, P < 0.01). Similarly, GTP-CHI mRNA induction in various tissues substantially increased within 4 hours compared to normal controls (P < 0.05, P < 0.01). It was also shown that hepatic and renal biopterin levels were positively correlated with glutamic pyruvic transaminase (GPT) and also blood urea nitrogen (BUN) values (both P < 0.01). In addition, treatment with recombinant bactericidal/permeability increasing protein (rBPI(21)) markedly reduced tissue biopterin and GTP-CHI mRNA levels, concomitant with significant decreases in GPT, BUN as well as D-lactate values. CONCLUSIONS: Biopterin synthesis and release may be involved in the development of endotoxin-induced multiple organ dysfunction, and early use of rBPI(21) is effective to inhibit marked GTP-CHI mRNA expression and biopterin formation following septic shock.

Animals↗