Download Notes on EMF affecting melatonin via nitric oxide

Notes on EMF affecting melatonin via
nitric oxide
Tryptophan
Like Serotonin, precursor to melatonin. Another reason why mel suppressed? EMF–
tryptophan–serotonin–melatonin
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1135961
Nitric oxide rapidly scavenges tyrosine and tryptophan radicals
Biochem J. 1995 September 15; 310(Pt 3): 745–749.
J P Eiserich, J Butler, A van der Vliet, C E Cross, and B Halliwell
Department of Internal Medicine, University of California, Davis, 95616, USA.
Abstract
By utilizing a pulse-radiolytic technique, we demonstrate for the first time that the rate
constant for the reaction of nitric oxide (.NO) with biologically relevant tyrosine and
tryptophan radicals (Tyr. and Trp. respectively) in amino acids, peptides and proteins is
of the order of (1-2) x 10(9) M-1.s-1. We also show that .NO effectively interferes with
electron-transfer processes between tryptophan and tyrosine residues in proteins
subjected to pulse radiolysis. The near diffusion-controlled rates of these reactions,
coupled with the increasingly recognized role of protein radicals in enzyme catalysis and
oxidative damage, suggest that Tyr. and Trp. are likely and important targets for .NO
generated in vivo.
EMF does not affect tryptophan directly.
http://cat.inist.fr/?aModele=afficheN&cpsidt=3236057
Inactivation of brain tryptophan hydroxylase by nitric oxide
Journal of neurochemistry (J. neurochem.) 1996, vol. 67, no3, pp. 1072-1077 (40 ref.)
Kuhn D. M. (1 2) ; Arthur R. E. (1)
Cellular and Clinical Neurobiology Program, Department of Psychiatry and Behavioral
Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, ETATSUNIS
(2) Center for Molecular Medicine and Genetics, Wayne State University School of
Medicine, Detroit, Michigan, ETATS-UNIS
(1)
Abstract
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Tryptophan hydroxylase, the initial and rate-limiting enzyme in the biosynthesis of the
neurotransmitter serotonin, is inactivated by nitric oxide (NO) and by the NO generators
sodium nitroprusside, diethylamine/NO, S-nitroso-N-acetylpenicillamine, and Snitrosocysteine. The inactivation occurs in an oxygen-free environment and is enhanced
by dithiothreitol and ascorbic acid. Protection against the effect of NO on tryptophan
hydroxylase is afforded by oxyhemoglobin, reduced glutathione, and exogenous Fe(II).
Catalase partially protects the enzyme from NO-induced inactivation, whereas both
superoxide dismutase and uric acid are without effect. These findings indicate that
tryptophan hydroxylase is a target for NO and suggest that critical iron-sulfur groups in
this enzyme serve as the substrate for NO-induced nitrosylation of the protein, resulting
in enzyme inactivation.
http://www.jbc.org/cgi/content/abstract/274/38/26907
J Biol Chem, Vol. 274, Issue 38, 26907-26911, September 17, 1999
Tryptophan 409 Controls the Activity of Neuronal Nitric-oxide Synthase by Regulating
Nitric Oxide Feedback Inhibition
(read carefully: could be important)
Subrata AdakDagger , Carol CrooksDagger , Qian WangDagger , Brian R. Crane§, John A.
Tainer§, Elizabeth D. Getzoff§, and Dennis J. StuehrDagger
From the Dagger Department of Immunology, Lerner Research Institute, Cleveland
Clinic, Cleveland, Ohio 44195 and the § Department of Molecular Biology and the Skaggs
Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037
The heme of neuronal nitric-oxide synthase participates in oxygen activation but also
binds self-generated NO during catalysis resulting in reversible feedback inhibition. We
utilized point mutagenesis to investigate if a conserved tryptophan residue (Trp-409),
which engages in pi -stacking with the heme and hydrogen bonds to its axial cysteine
ligand, helps control catalysis and regulation by NO. Surprisingly, mutants W409F and
W409Y were hyperactive compared with the wild type regarding NO synthesis without
affecting cytochrome c reduction, reductase-independent N-hydroxyarginine oxidation,
or Arg and tetrahydrobiopterin binding. In the absence of Arg, NADPH oxidation
measurements showed that electron flux through the heme was actually slower in the
Trp-409 mutants than in wild-type nNOS. However, little or no NO complex accumulated
during NO synthesis by the mutants, as opposed to the wild type. This difference was
potentially related to mutants forming unstable 6-coordinate ferrous-NO complexes
under anaerobic conditions even in the presence of Arg and tetrahydrobiopterin. Thus,
Trp-409 mutations minimize NO feedback inhibition by preventing buildup of an inactive
ferrous-NO complex during the steady state. This overcomes the negative effect of the
mutation on electron flux and results in hyperactivity. Conservation of Trp-409 among
different NOS suggests that the ability of this residue to regulate heme reduction and NO
complex formation is important for enzyme physiologic function.
http://www.jneurosci.org/cgi/content/abstract/17/19/7245
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Volume 17, Number 19, Issue of October 1, 1997 pp. 7245-7251
Molecular Mechanism of the Inactivation of Tryptophan Hydroxylase by Nitric Oxide:
Attack on Critical Sulfhydryls that Spare the Enzyme Iron Center
Received May 27, 1997; revised July 14, 1997; accepted July 16, 1997.
Donald M. Kuhn1, 2 and Robert Arthur Jr1
1 Cellular and Clinical Neurobiology Program, Department of Psychiatry and Behavioral
Neurosciences, and 2 Center for Molecular Medicine and Genetics, Wayne State
University School of Medicine, Detroit, Michigan 48201
Tryptophan hydroxylase (TPH), the initial and rate-limiting enzyme in the biosynthesis of
the neurotransmitter serotonin (5-HT), is irreversibly inactivated by nitric oxide (NO). We
have expressed brain TPH as a recombinant glutathione-S-transferase fusion protein and
delineated the catalytic domain of the enzyme as the region spanning amino acids 99-444.
Highly purified TPH catalytic core, like the native enzyme from brain, is inactivated by
NO in a concentration-dependent manner. Removal of iron from TPH produces an
apoenzyme with low activity that can be reconverted to its highly active holo-form by the
addition of ferrous iron. Apo-TPH exposed to NO cannot be reactivated by iron.
Treatment of holo-TPH (iron-loaded) with the disulfide 5,5'-dithio-bis (2-nitrobenzoic
acid) (DTNB) causes an inactivation of TPH that is readily reversed by dithiothreitol
(DTT). DTNB-treated TPH [sulfhydryl (SH)-protected] exposed to NO is returned to full
activity by thiol reduction with DTT. The inactivation of native TPH by NO cannot be
reversed by either iron or DTT. These data indicate that NO inactivates TPH by selective
action on critical SH groups (i.e., cysteine residues) while sparing catalytic iron sites
within the enzyme. The results are interpreted with reference to the substituted
amphetamines, which are neurotoxic to 5-HT neurons, that inactivate TPH in vivo and are
now known to produce NO and other reactive oxygen species in vivo.
Serotonin
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids
=10465443&dopt=Abstract
Nitric oxide transforms
neuromodulation.
serotonin
into
an
inactive
form
and
this
affects
Fossier P, Blanchard B, Ducrocq C, Leprince C, Tauc L, Baux G.
Laboratoire de Neurobiologie Cellulaire et Moleculaire, CNRS, Gif sur Yvette, France.
Nitric oxide is a highly reactive molecule, diffusible and therefore ubiquitous in the
central nervous system. Consequently, nitric oxide or nitric oxide-derived nitrogen oxides
must enter into contact with neuromodulators and they can modify these molecules,
especially monoamines, and thus change their regulatory action on synaptic transmission.
We tested this possibility on a well-known, identified cholinergic synapse of Aplysia
buccal ganglion, in which we have found that evoked acetylcholine release was decreased
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by extracellularly applied serotonin. We show that this modulatory effect of serotonin was
largely reduced not only in the presence of 3-morpholinosydnonimine, a nitric oxide
donor, but also when endogenous nitric oxide synthase was activated. We have shown
that this decrease in the serotonin effect is due to the formation of chemical derivatives of
serotonin, mainly a symmetric serotonin dimer, 4-nitroso-serotonin and 4-nitro-serotonin,
which are ineffective in reproducing the modulatory effect of serotonin. Serotonin is
involved in the regulation of several central functions, such as sleep-wake activity or
mood. The consequences of chemical modifications of serotonin by nitric oxide must be
taken into account in physiological as well as pathological situations. In addition, our
results highlight the importance of the physiological implications of interactions between
free radicals and neuromediators in the nervous system.
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