Cysteine As A Substrate

himsahimsa

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Cysteine is the limiting substrate for:

Glutathion Peroxidase
Superoxide Dysmutase
Thyroperoxidase

These are all very important.

For instance acetaminophen depletes superoxide dysmutase in the liver so rapidly that 8000mg (or less) acetaminophen can kill the liver and thus the owner of that liver. Without Thyroperoxidase sever damage occurs to the thyroid gland as a result of just making its hormones. Glutathion Peroxidase is used directly in the liver and also everywhere as the peroxidation backstop for immune system activity.

How can restricting cysteine intake not be a problem?
 

Wilfrid

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Good post.

Cysteine ,like methionine and tyrosine , is one of the most important human's antioxydant amino acid.

Differential effects of cysteine and methionine residues in the antioxidant activity of human serum albumin.
Emmanuel Bourdon, Nadine Loreau, Laurent Lagrost, Denis Blache
Faculté de Médecine, INSERM U498-Biochimie des Lipoprotéines, Université de Bourgogne, 7, blvd Jeanne d'Arc, BP 87900 21079, Dijon, France.
Free Radical Research (Impact Factor: 3.28). 02/2005; 39(1):15-20. DOI:10.1080/10715760400024935
Source: PubMed
ABSTRACT Antioxidant properties of human serum albumin (HSA) may explain part of its beneficial role in various diseases related to free radical attack. In the present study, the antioxidant role of Cys and Met was studied by copper-mediated oxidation of human low density lipoproteins and by free radical-induced blood hemolysis which essentially assessed metal-chelating and free radical scavenging activities, respectively. Mild conditions were set up to specifically modify Cys and Met residues by N-ethylmaleimide (NEM) and chloramine T treatments, respectively. We found that Met and Cys accounted for 40-80% of total antioxidant activity of HSA. Copper binding to HSA was decreased by about 50% with chloramine T treatment of Met whereas no change was observed after NEM treatment of Cys. Although other amino acid residues are likely to be involved in anti-/prooxidant properties of HSA, from our data, we propose that Cys chiefly works as a free radical scavenger whereas Met mainly acts as a metal chelator.

That is to say I'm ,too, still confused about Ray's take on cysteine....
 

Blossom

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Here is what I know about Ray's stance on cysteine, in large doses along with methionine and tryptophan it inhibits thyroid function. I will find the source asap. I also read about toxins in the manufacturing process of single amino acids being a concern as well as the bodies utilization as compared to whole protein sources. I'm not sure how this applies to substrates.
 

Blossom

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These two articles specifically:
Tryptophan,serotonin and aging
Gelatin, stress and longevity
 

himsahimsa

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All that looks speculative. I read through everything on the RP site and don't see any mechanism discussed. Maybe in the footnotes. I did read all the footnotes but could have missed something. Even if it is somewhat anti-thyroid, being short the glutathion based enzymes has got to be very bad.

I took about 1.2 grams N-Acetyl cysteine almost every day for years and did not notice any ill effect and was basically in good health.

(I run low, 97.4F DEG average, but I always have, since I was little. I know because I have tracked it. I'm trying to goose it up a degree or so now, to no avail, and am being OCD scrupulous about the pro and anti thyroid materials. It's off the subject but any advice on that would be a help. I am homeostatic like a rock. Trying to move my BMR off the peg is not happening.)
 

himsahimsa

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Here is an abstract RP used. The author was able to reverse thyroid inhibition by increasing available iodide. This is in vitro. I don't know how 12 or 18 millimoles of iodide compares to its concentration in a living thyroid in a living neck. I'm sure it's known. Also, penetration of circulating free inhibitory amino acids into a living thyroid and thus their ability to act on the enzymes is not addressed.
Braz J Med Biol Res. 2000 Mar;33(3):355-61.
Thyroid peroxidase activity is inhibited by amino acids.
Carvalho DP, Ferreira AC, Coelho SM, Moraes JM, Camacho MA, Rosenthal D.
Normal in vitro thyroid peroxidase (TPO) iodide oxidation activity was completely inhibited by a hydrolyzed TPO preparation (0.15 mg/ml) or hydrolyzed bovine serum albumin (BSA, 0.2 mg/ml). A pancreatic hydrolysate of casein (trypticase peptone, 0.1 mg/ml) and some amino acids (cysteine, tryptophan and methionine, 50 microM each) also inhibited the TPO iodide oxidation reaction completely, whereas casamino acids (0.1 mg/ml), and tyrosine, phenylalanine and histidine (50 microM each) inhibited the TPO reaction by 54% or less. A pancreatic digest of gelatin (0.1 mg/ml) or any other amino acid (50 microM) tested did not significantly decrease TPO activity. The amino acids that impair iodide oxidation also inhibit the TPO albumin iodination activity. The inhibitory amino acids contain side chains with either sulfur atoms (cysteine and methionine) or aromatic rings (tyrosine, tryptophan, histidine and phenylalanine). Among the amino acids tested, only cysteine affected the TPO guaiacol oxidation reaction, producing a transient inhibition at 25 or 50 microM. The iodide oxidation inhibitory activity of cysteine, methionine and tryptophan was reversed by increasing iodide concentrations from 12 to 18 mM, while no such effect was observed when the cofactor (H2O2) concentration was increased. The inhibitory substances might interfere with the enzyme activity by competing with its normal substrates for their binding sites, binding to the free substrates or reducing their oxidized form.

RP also talks about increased longevity associated with the deficiency of these amino acids independently of this anti-thyroid effect. So...
 

Blossom

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Quote from Ray Peat March 2005 Context for Asthma
"The selection of proteins should minimize the amino acids tryptophan(which is the precursor of serotonin) and cysteine( which like tryptophan, suppresses the thyroid function) by including gelatin and fruits."
 

Blossom

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Quote from Ray Peat's January 2001 newsletter on the topic Fibrosis:
" Too much glutamine acid, aspartic acid and cysteine can be directly cytotoxic, and the metabolites of cysteine include proinflammatory homocysteine, which can disrupt collagen structure."
 

nograde

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metabolites of cysteine include proinflammatory homocysteine, which can disrupt collagen structure.

I think that's wrong. Homocysteine is either shunted downwards to cysteine (using B6 as cofactor) or recycled back to methionine (using folate, betaine and choline as cofactor). As far as I know there's no pathway going from cysteine back to homocysteine. See here: http://lpi.oregonstate.edu/infocenter/v ... 6diag.html

There's no doubt that elevated homocysteine is really bad news, even in "conservative" circles it's implicated in many diseases. I think its clear that avoiding homocysteine buildup is an important goal. However how should we achieve that?

  • Restrict methionine (the precursor)
  • Watch out for good B6 status to transform homocysteine down to cysteine (which RP says is bad for thyroid)
  • Watch out for good Folate, betaine, choline status to recycle it back to methionine (which RP says is bad)

And how does glycine play into all this? Is there any new information on Ray's stance on this topic?
 

dfspcc20

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Aren't humans also able to biosynthesize cysteine into taurine?
I've been wondering what determines how well (or poorly) we make that conversion.
 

Peater Piper

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Aren't humans also able to biosynthesize cysteine into taurine?
I've been wondering what determines how well (or poorly) we make that conversion.
Indeed, and does consuming (or supplementing) taurine cause the cysteine to take a different path? It's a pretty complicated process.
 
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