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Melanoma Needs Glutamine To Grow And Dies Without It

haidut

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In support of Ray's opinion on amino acids like glutamine and arginine fueling cancer growth, this study found that melanoma cancer needs glutamine for its growth and without a steady supply of glutamine the cancer dies.
So, glutamine and arginine restriction / depletion seem to be viable approaches to cancer control / cure and as far as I know there is a clinical trial in Germany for colon cancer using the chemical L-NAME (arginine depletor). If someone knows of clinical trial or human study using glutamine restriction / depletion please share it on the forum.

http://beaker.sanfordburnham.org/2015/0 ... er-growth/

"...Researchers at Sanford-Burnham have discovered that without a source of glutamine—one of the 20 amino acids used to build proteins—melanoma cells will stop proliferating and die. Their craving for glutamine stems from their ability to “abuse” this essential nutrient by using it as an additional source of carbon and energy. The findings present a rational basis for a treatment strategy that limits the supply of glutamine to tumors, potentially through nutritional interventions or inhibitors of glutamine uptake. The results of the study appear online in Oncotarget today."
 
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Milk seems to have lots of glutamate, but I don't know whether it's the whey or the casein part.
 

haidut

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Such_Saturation said:
Milk seems to have lots of glutamate, but I don't know whether it's the whey or the casein part.

Actually both - whey and casein each have 17%-20% glutamic acid per weight.
 

haidut

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Btw, one of the hot topics in cancer research right now is inhibition of glutamine synthetase (GS). That results in glutamine depletion. Among the natural and effective inhibitors of GS are alanine and glycine, even at physiological concentrations.
https://en.wikipedia.org/wiki/Glutamine ... Inhibition

"...Inhibition of GS has largely focused on amino site ligands.[6] Other inhibitors are the result of glutamine metabolism: tryptophan, histidine, carbamoyl phosphate, glucosamine-6-phosphate, cytidine triphosphate (CTP), and adenosine monophosphate (AMP).[5][8][24] Other inhibitors/regulators are glycine and alanine. Alanine, glycine, and serine bind to the glutamate substrate site. GDP, AMP, ADP bind to the ATP site.[6] L-serine, L-alanine, and glycine bind to the site for L-glutamate in unadenylated GS. The four amino acids bind to the site by their common atoms, “the main chain” of amino acids.[5] Glutamate is another product of glutamine metabolism; however, glutamate is a substrate for GS inhibiting it to act as a regulator to GS.2 Each inhibitor can reduce the activity of the enzyme; once all final glutamine metabolites are bound to GS, the activity of GS is almost completely inhibited.[8] Many inhibitory input signals allows for fine tuning of GS by reflecting nitrogen levels in the organism."

Given the importance of GS in all types of cancer, it is not surprising that glycine protects against cancer. Ray knows his stuff once again.
 
J

jb116

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Shouldn't confuse glutamate with glutamine however. Two different amino acids.
 

haidut

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jb116 said:
Shouldn't confuse glutamate with glutamine however. Two different amino acids.

Yes, the melanoma study is on glutamine and the link on glycine being inhibitor is also on glutamine. Glutamine synthetase makes glutamine out of glutamate. So, I guess suppressing it too much could lead to issues with excitotoxicity. Even then, it's probably preferable to cancer growth.
Other known inhibitors are copper, zinc, and vitamin B6 (P5P).
 

Elephanto

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Yes, the melanoma study is on glutamine and the link on glycine being inhibitor is also on glutamine. Glutamine synthetase makes glutamine out of glutamate. So, I guess suppressing it too much could lead to issues with excitotoxicity. Even then, it's probably preferable to cancer growth.
Other known inhibitors are copper, zinc, and vitamin B6 (P5P).

What about the fact that glutamine synthesase is inhibited by nitric oxide, hyperammonia and ndma receptors activation, and increased by biotin, magnesium etc ? It seems like general Peat recommendations would lead to higher Glutamine Synthetase.

Glutamine synthetase activity and glutamine content in brain: modulation by NMDA receptors and nitric oxide. - PubMed - NCBI

Glutamine synthetase in brain: effect of ammonia. - PubMed - NCBI

Effect of glutamine on glutathione, IGF-I, and TGF-beta 1. - PubMed - NCBI

Glutamine (7g/day) decrease IGF-1, TGF-Beta, increase glutathione.

It's also found low in alzheimer and autism. Has neuroprotective qualities.

Oncogenes and Tumor Suppressors Regulate Glutamine Metabolism in Cancer Cells

"Other experiments also show a relationship between p53 and glutamine in regards to tumor suppression. Oral glutamine supplementation increases phosphorylation of p53 and apoptosis in DMBA-induced mammary tumors.5,22 In this experiment, the levels of phosphorylated p53 in tumors of rats given glutamine supplementation were higher than those without glutamine supplementation. In addition, the expression of p21Waf1/Cip1, PTEN, mdm2, and IGF-IR, which are target proteins of p53, was regulated by glutamine supplementation"
 

Elephanto

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From reading further I think the problem is mainly from glutaminase which retransform glutamine into glutamate. If glutaminase is minimized then glutamine is probably beneficial. Glutaminase is activated by ammonia, phosphate. apparently in colon cancer if glutaminase is desactivated, cancer stops to grow.
 

Jarman

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So how to heal leaky gut if one can't take l-glutamine supplement? There's no win-win situation here. What are the alternatives to heal leaky gut?
 

Peater Piper

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So how to heal leaky gut if one can't take l-glutamine supplement? There's no win-win situation here. What are the alternatives to heal leaky gut?
I for one don't think that glutamine is all bad, but even if restriction is preferable, supplementing for a month or two to improve gut health probably outweighs the potential negatives. Collagen/glycine also help heal the gut and could potentially mitigate some of the downsides of glutamine.

In terms of glutamine and cancer, I've actually read of some potential benefits to supplementing glutamine because it becomes so depleted in cancer patients. Also, cancer, ever so adaptable, can survive glutamine deprivation by relying on other nutrients. The cancer patient may suffer more from glutamine deprivation than the cancer does.

Cancer tumors can establish new nutrient sources; study finds how
 

burtlancast

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Herpes virus is also known to be triggered by arginine-rich foods, while being inhibited by lysine.
 

haidut

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Herpes virus is also known to be triggered by arginine-rich foods, while being inhibited by lysine.

The inhibition by lysine has two reasons - opposition to NO and also to serotonin. Lysine is a serotonin antagonist as we posted in another thread. You can stop most viruses from propagating by blocking 5-HT2A. The entire 5-HT2 family controls the immune system and opposing 5-HT2 with drugs like cyproheptadine can treat everything from herpes, to Ebola, to JCV, to cancer.
 

Luann

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I was studying the apocrine glands and why puberty makes kids stink. Glutamine feeds the bacteria that produce smelly short-chain fats, and estrogen seems to spur the glutamine synthetase.


Effect of 17β-estradiol administration on hepatic expression of glutamine synthetase, β-catenin, and GPR30 in young and aged beef cows

Estradiol modulation of astrocytic form and function: Implications for hormonal control of synaptic communication


"estradiol increases the expression of a number of glial-specific genes, including glutamine synthetase".
 

haidut

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I was studying the apocrine glands and why puberty makes kids stink. Glutamine feeds the bacteria that produce smelly short-chain fats, and estrogen seems to spur the glutamine synthetase.


Effect of 17β-estradiol administration on hepatic expression of glutamine synthetase, β-catenin, and GPR30 in young and aged beef cows

Estradiol modulation of astrocytic form and function: Implications for hormonal control of synaptic communication


"estradiol increases the expression of a number of glial-specific genes, including glutamine synthetase".

Interesting, thanks! So, inhibiting estrogen helps control melanoma growth in more than one way. Btw, glutamine feeds not just melanoma. Pretty much all cancers rely on this amino acid to synthesize fat and glucose. But why do kids have elevated glutamine levels?
 

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