Search results for "Tetrahydrobiopterin"
showing 10 items of 18 documents
Identification of 5,6,7,8-tetrahydropterin and 5,6,7,8-tetrahydrobiopterin in Drosophila melanogaster.
1988
Summary Using reversed-phase high-performance liquid chromatography with electrochemical detection we have demonstrated the occurrence of 5,6,7,8-tetrahydropterin and 5,6,7,8-tetrahydrobiopterin in Drosophila melanogaster . The former is the first time that has been detected in vivo . The identification has been based on the retention times, hydrodinamic voltagrams and the differential concentration in three strains of Drosophila melanogaster . Compared to the wild type, the Punch 2 mutant has diminished levels of both pteridines, whereas Henna-recessive 3 lacks completely tetrahydropterin and has increased levels of tetrahydrobiopterin, as expected according to their biochemical lesions.
Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: Possible therapeutic targets?
2013
International audience; Nitric oxide (• NO) is synthetized enzymatically from L-arginine (L-Arg) by three NO synthase isoforms, iNOS, eNOS and nNOS. The synthesis of NO is selectively inhibited by guanidino-substituted analogs of L-Arg or methylarginines such as asymmetric dimethylarginine (ADMA), which results from protein degradation in cells. Many disease states, including cardiovascular diseases and diabetes, are associated with increased plasma levels of ADMA. The N-terminal catalytic domain of these NOS isoforms binds the heme prosthetic group as well as the redox cofactor, tetrahydrobiopterin (BH 4) associated with a regulatory protein, calmodulin (CaM). The enzymatic activity of NOS…
Nitric Oxide Synthesis in Vascular Physiology and Pathophysiology
2015
Nitric oxide (NO) is produced by three NO synthase (NOS) isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). Under physiological conditions, vascular NO is produced by eNOS and nNOS, with both playing atheroprotective roles. Under pathological conditions, iNOS can be induced and eNOS may become uncoupled. iNOS produces a large amount of NO, induces vascular dysfunction, and promotes atherogenesis. Uncoupled eNOS generates superoxide instead of NO and contributes significantly to endothelial dysfunction and atherogenesis. Major mechanisms of eNOS uncoupling include depletion of tetrahydrobiopterin, an essential co-factor for the eNOS enzyme, and deficiency of L-a…
eNOS Uncoupling in Cardiovascular Diseases - the Role of Oxidative Stress and Inflammation
2013
Many cardiovascular diseases and drug-induced complications are associated with - or even based on - an imbalance between the formation of reactive oxygen and nitrogen species (RONS) and antioxidant enzymes catalyzing the break-down of these harmful oxidants. According to the “kindling radical” hypothesis, the formation of RONS may trigger in certain conditions the activation of additional sources of RONS. According to recent reports, vascular dysfunction in general and cardiovascular complications such as hypertension, atherosclerosis and coronary artery diseases may be connected to inflammatory processes. The present review is focusing on the uncoupling of endothelial nitric oxide synthas…
Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease.
2013
Nitric oxide (NO) produced by the endothelial NO synthase (eNOS) is an antihypertensive, antithrombotic and anti-atherosclerotic molecule. Hypercholesterolemia leads to a reduction in vascular NO bioavailability. This is attributed to a dysfunction of the eNOS enzyme and a reduced eNOS activity. NADPH oxidase-mediated oxidative stress leads to oxidation of tetrahydrobiopterin (BH4), the essential cofactor of eNOS. In BH4 deficiency, oxygen reduction uncouples from NO synthesis, thereby converting eNOS to a superoxide-producing enzyme. As a consequence of eNOS uncoupling, NO production is reduced and the pre-existing oxidative stress is enhanced, which contribute significantly to atherogenes…
Regulation of pteridine biosynthesis and aromatic amino acid hydroxylation in Drosophila melanogaster
1989
The relationship between high dietary levels of aromatic amino acid and regulation of pteridines in Drosophila eyes was examined by measuring changes in pool levels of six pterins in the wild type and mutants and amino acid pool levels in flies that carry mutations for pteridine biosynthesis. The effect upon relative viability and developmental times was also analyzed; relative viability was affected by L-phenylalanine, L-tryptophan, and L-tyrosine in decreasing order and the D-amino acids had little or no effect. The changes in concentration of biopterin, dihydrobiopterin, pterin, sepiapterin, drosopterins, and isoxanthopterin showed a characteristic pattern of increased and/or decreased a…
Implication of eNOS Uncoupling in Cardiovascular Disease
2017
Under physiological conditions, nitric oxide (NO) is produced in the vasculature mainly by the endothelial nitric oxide synthase (eNOS). Endothelial NO relaxes blood vessels, inhibits platelet activity, and protects against atherosclerosis. Under pathological conditions such as hypertension, diabetes, and hypercholesterolemia, eNOS may become uncoupled. Uncoupled eNOS generates superoxide at the expense of NO and contributes substantially to oxidative stress and endothelial dysfunction. Major mechanisms of eNOS uncoupling include deficiency of the eNOS cofactor tetrahydrobiopterin, deficiency of the eNOS substrate L-arginine, and eNOS S-glutathionylation. Reversal of eNOS uncoupling may rep…
Prevention of Atherosclerosis by Interference with the Vascular Nitric Oxide System
2009
Nitric oxide (NO) produced by endothelial NO synthase (eNOS) represents an anti-atherosclerotic principle. NO bioavailability is decreased in atherosclerosis due to increased NO inactivation by reactive oxygen species and reduced NO synthesis. Various types of vascular pathophysiology are associated with oxidative stress, with NADPH oxidases as the major source of reactive oxygen species. These inactivate NO. Also, oxidative stress is likely to be the main cause for oxidation of the essential NOS cofactor, tetrahydrobiopterin (BH(4)). A lack of BH(4) leads to eNOS uncoupling (i.e., uncoupling of oxygen reduction from NO synthesis in eNOS). Based on these pathomechanisms, the therapeutic pot…
Cardiovascular and Endocrine Properties of L-Tryptophan in Combination with Various Diets
1991
Brain serotonin neurons are intimately involved in a number of relevant physiological functions such as cardiovascular regulation, neuroendocrine output from the anterior pituitary (e.g. ACTH, prolactin), regulation of behavior (e.g. agression, sleep, locomotor and sexual behavior), mood or appetite control (Fernstrom, 1983; Lehnert et al., 1987; Spring et al., 1987; Wurtman, 1987). The synthesis of brain serotonin is dependent on the availability of the large neutral amino acid L-tryptophan that is hydroxylated to 5-L-hydroxytryptophan and subsequently decarboxylated to yield serotonin. The rate-limiting enzyme tryptophan hydroxylase has a Michaelis constant of approximately 2–3 x 10−5 M w…
Arginine and nitric oxide synthase: regulatory mechanisms and cardiovascular aspects
2014
L-Arginine (L-Arg) is a conditionally essential amino acid in the human diet. The most common dietary sources of L-Arg are meat, poultry and fish. L-Arg is the precursor for the synthesis of nitric oxide (NO); a key signaling molecule via NO synthase (NOS). Endogenous NOS inhibitors such as asymmetric-dimethyl-L-Arg inhibit NO synthesis in vivo by competing with L-Arg at the active site of NOS. In addition, NOS possesses the ability to be "uncoupled" to produce superoxide anion instead of NO. Reduced NO bioavailability may play an essential role in cardiovascular pathologies and metabolic diseases. L-Arg deficiency syndromes in humans involve endothelial inflammation and immune dysfunctions…