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Glutathione Synthesis and supplying necessary ingredients

Jarod

Senior Member
Messages
784
Location
planet earth
Nice open topic thread to discuss anything related to better understanding Glutathione synthesis, receptors, SNP's, and supplying raw materials in general needed for glutathione synthesis in on topic.
 

Jarod

Senior Member
Messages
784
Location
planet earth
Any thoughts on how to get this cystine/glutamate antiporter process working more effectively? Or if it is problematic for some of us?



Dr Blaylock mentioned it in his video here at 2:10

System xc⁻ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS.


Bridges RJ, Natale NR, Patel SA.
Source

Center for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana 59812, USA. richard.bridges@umontana.edu

Abstract

System x(c)(-) is an amino acid antiporter that typically mediates the exchange of extracellular l-cystine and intracellular L-glutamate across the cellular plasma membrane. Studied in a variety of cell types, the import of L-cystine through this transporter is critical to glutathione production and oxidative protection. The exchange-mediated export of L-glutamate takes on added significance within the CNS, as it represents a non-vesicular route of release through which this excitatory neurotransmitter can participate in either neuronal signalling or excitotoxic pathology. When both the import of L-cystine and the export of L-glutamate are taken into consideration, system x(c)(-) has now been linked to a wide range of CNS functions, including oxidative protection, the operation of the blood-brain barrier, neurotransmitter release, synaptic organization, viral pathology, drug addiction, chemosensitivity and chemoresistance, and brain tumour growth. The ability to selectively manipulate system x(c)(-), delineate its function, probe its structure and evaluate it as a therapeutic target is closely linked to understanding its pharmacology and the subsequent development of selective inhibitors and substrates. Towards that goal, this review will examine the current status of our understanding of system x(c)(-) pharmacology and the structure-activity relationships that have guided the development of an initial pharmacophore model, including the presence of lipophilic domains adjacent to the substrate binding site. A special emphasis is placed on the roles of system x(c)(-) within the CNS, as it is these actions that are among the most exciting as potential long-range therapeutic targets.
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

http://www.ncbi.nlm.nih.gov/pubmed/21564084

Some good images included in the link
 

Jarod

Senior Member
Messages
784
Location
planet earth
Good image that illustrates what makes glutathione. Glutamate + Cysteine +Glycine= Glutathione


glutathione.jpg


glutat2.jpg
 

triffid113

Day of the Square Peg
Messages
829
Location
Michigan
Idk. But I contribute this: http://pubs.acs.org/doi/abs/10.1021/jf8034429

Olive Phenolics Increase Glutathione Levels in Healthy Volunteers

Francesco Visioli, Roswitha Wolfram, Doriane Richard, Muhammad Imran Chong B. Abdullah and Roberto Crea
J. Agric. Food Chem., 2009, 57 (5), pp 1793–1796

Abstract
Several in vitro and in vivo studies have shown that olive phenols exert potent biological activities including, but not limited to, antioxidant actions. These activities are shared by phenols found in olives, olive oil, and olive mill wastewater (OMWW). The aim of this study was to investigate whether a commercially available OMWW preparation could influence some parameters of oxidative status in healthy human volunteers. Ninety-eight healthy subjects with normal body weight were recruited, and 5 mL of blood was drawn from their antecubital vein after an overnight fast of at least 12 h. After this, subjects were asked to ingest 2 mL of a commercially available OMWW preparation. Another 5 mL of blood was drawn 1 h after ingestion of the preparation. Plasma antioxidant capacity and total and reduced glutathione were measured. No difference in plasma antioxidant capacity was observed between baseline and 1 h after the ingestion of the extract. Conversely, a significant increase in total plasma glutathione concentration was measured. This increase involved both the reduced and oxidized forms of glutathione; hence, their ratio was unaffected by the treatment. The observed effects of OMWW on glutathione levels might be governed by the antioxidant response element (ARE)-mediated increase in phase II enzyme expression, including that of γ-glutamylcysteine ligase and glutathione synthetase. Future studies on groups of individuals who may benefit from an increase in their glutathione levels, for example, the elderly, will further elucidate the biological activities of this formulation.
 

triffid113

Day of the Square Peg
Messages
829
Location
Michigan
Huh. Don't know why anyone would take glutamate. It says in Wiki:
All meats, poultry, fish, eggs, dairy products, and kombu are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources. 30 to 35% of the protein in wheat is glutamic acid.

---

Ok, here's something important to contribute: it takes selenium to make glutathione and many areas of the U.S. are selenium deficient. Selenium is also important to the thyroid gland (it is the antioxidant needed by the thyroid). So a good multi vitamin or eating a few Brazil nuts every day can help you get the selenium you need.
 
Messages
66
Any thoughts on how to get this cystine/glutamate antiporter process working more effectively? Or if it is problematic for some of us?

This was an additional edit I made back on my post about the SLC1a1 genewhich encodes for the EAAT1 enzyme. This article has some very good information about glutamate transport as a potential player in the pathology of OCD, as well as information in regarding the antiporter and glutathione production. (and other illnesses).

"I found out why NAC helps people with ocd and how it modulates glutamate in this article.
http://www.ocd.yale.edu/researchers/329_114509_Pittenger et al (2011) Glutamate abnormalities in OCD.pdf

"Indeed, excess glutamate has long been known to lead to neuronal death, a phenomenon known as excitotoxicity (Olney, 1969). Glutamate concentration is therefore tightly regulated. The principal mode of regulation is through high-affinity glutamate transporters, which efficiently remove glutamate from the perisynaptic and extrasynaptic spaces (Danbolt, 2001). Quantitatively, glutamate transporters on glial cells – principally astrocytes – are responsible for the majority of glutamate removal; these astrocytic glutamate transporters are a target of the glutamate-modulating drug riluzole, which has shown promise in the treatment of refractory OCD (Pittenger et al., 2008a). A smaller fraction of glutamate is removed by the neuronal glutamate transporter, EAAC1/EAAT3; as reviewed below, polymorphisms in the gene encoding this transporter have been repeatedly associated with OCD in recent studies (Arnold et al.,2006; Dickel et al., 2006; Stewart et al., 2007; Shugart et al., 2009). Finally, glutamate is also transported into glial cells in exchange for the oxidized amino acid cystine via the glutamate-cystine antiporter; undersome circumstances the activity of this antiporter, which is influenced by the drug N-acetylcysteine, may be the principal determinant of baseline levels of extrasynaptic glutamate (Kalivas, 2009)"
 

triffid113

Day of the Square Peg
Messages
829
Location
Michigan
And yet doctors that treat autistics say that frequently NAC is a problem for autistics and Freddd say it completely stops methylation for him. Would you not say that autists have OCD? Because I think we are the ultimate in OCD and to me it does not feel at all like an excitotoxicity attack such as I have gotton from MSG. The above may be an important clue, idk, but treat it with caution. I personally would not take NAC but I do take a cruciferous veggie extract every day (which contains cysteine) and I often take milk thistle and garlic pils - both also containing cysteine. I am never low in cysteine and in fact run just a tad high due to my supplements, with no adverse effects. idk what form the cysteine I get is in but I know I have no problem with it in that form so I would never take NAC.
 
Messages
66
I do not use NAC for my OCD. I was just adding that bit in there because I felt like the OCD article, which speaks about NAC as a modulator of extra and intercellular glutamate via the antiporter, does a good job of describing the whole process. I guess increased cystine or cysteine is just one possible way to increasing glutathione but perhaps not the only one. I do not take NAC for OCD but I am interested in the possible role of high glutamate activity in OCD, and the possible ways of lowering it. If you search clinical trials of NAC for OCD they exist. I don't know so much about NAC for autism (because I haven't read into it).
 
Messages
15,786
Now bear in mind this issue was found in rats at extremely high dosages, as many things cause problems at high doses.
Do you have a link for that? Google scholar is bringing up too many results to be useful, and the early ones are all saying acetylcysteine inhibits hypoxia and prevents hypoxia-associated damage.

Edit: is it www.turkjbiochem.com/2008/058-063.pdf‎ ?

According to that, 100mg per kg was harmful, whereas 50mg was beneficial. The 100mg would come out to 7,000mg per day for the average person, whereas the beneficial dose would be 3,500mg per day.

I take 1,800mg per day, which seems plenty for a beneficial effect.
 
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66