Cysteine is the sulfur-containing amino acid that is the key determinant of the protein structure — it is the only amino acid that forms the disulfide bonds (the covalent bonds between the sulfur atoms of two cysteine residues), and these disulfide bonds are the primary mechanism by which the protein tertiary and quaternary structure is stabilised. The disulfide bonds are the most important covalent bonds in the proteins — they are formed between the sulfhydryl groups of two cysteine residues and they are the primary determinant of the three-dimensional structure of the proteins, the stability of the proteins, and the biological activity of the proteins. The disulfide bonds are particularly important in the structural proteins (keratin, collagen, elastin), in the enzymes (the disulfide bonds stabilise the enzyme active site and maintain the catalytic efficiency), and in the immune proteins (the disulfide bonds are essential for the structure and the function of the antibodies, the cytokines, and the growth factors). Without adequate cysteine and disulfide bond formation, the protein structure is unstable, the connective tissue is weak, and the immune function is impaired — the hallmark of the cysteine deficiency and of the impaired protein structure. The typical dietary cysteine intake from the protein-rich foods (meat, fish, poultry, eggs, dairy) is 1-2g daily, and the body can synthesise the cysteine from the methionine (through the transsulfuration pathway, which requires the vitamin B6 and the serine), making it a conditionally essential amino acid — but during the periods of the high sulfur amino acid demand (wound healing, skin disorders, heavy metal detoxification), the dietary cysteine intake may be insufficient and the supplementation may be beneficial.
Cysteine and the Glutathione Synthesis
Cysteine is also the rate-limiting amino acid for the synthesis of the glutathione (the most important intracellular antioxidant, which is present in all cells at millimolar concentrations) — the glutathione is the tripeptide (gamma-glutamyl-cysteinyl-glycine) that is the primary defence against the oxidative stress, the electrophilic toxins, and the reactive nitrogen species. The cysteine is the rate-limiting amino acid for the glutathione synthesis because its concentration in the cells is the lowest of the three glutathione precursors (the other two are glutamate and glycine), and therefore it determines the maximum rate of the glutathione synthesis. Without adequate cysteine and glutathione synthesis, the cells are vulnerable to the oxidative stress, the detoxification is impaired, and the ageing accelerates — the hallmark of the cysteine deficiency and of the low glutathione states. The NAC (N-acetylcysteine) is the most commonly used supplement for the cysteine and glutathione support — it is a cysteine precursor that is rapidly absorbed from the intestine and converted to the cysteine in the liver, and it is the standard of care for the acetaminophen overdose and for the chronic liver disease.
The clinical importance of the cysteine for the glutathione synthesis and for the immune function is underscored by the observation that the NAC supplementation improves the glutathione levels and reduces the oxidative stress in people with the chronic diseases and in the healthy older adults. A meta-analysis of 10 RCTs in over 500 participants with the COPD found that the NAC supplementation at 600-1800mg daily significantly reduced the exacerbation rate (by 20-30%), improved the lung function (by 10-15%), and reduced the oxidative stress markers (by 15-20%) — demonstrating the potent antioxidant and anti-inflammatory effect of the NAC in humans.
Practical Application
For general cysteine supplementation for the glutathione support and for the connective tissue health, the evidence-based approach is to supplement with 600-1800mg of NAC daily (as the NAC capsules or powder, taken in divided doses of 600mg, 2-3 times per day on the empty stomach). The NAC should be taken on the empty stomach (30-60 minutes before the meals or 2 hours after the meals) for the optimal absorption, and it should be taken with the vitamin C (which recycles the glutathione and which protects the cysteine from the oxidation). The NAC is generally well-tolerated with no significant adverse effects at doses up to 3000mg daily, and it does not have any known drug interactions — though it may cause the gastrointestinal symptoms (nausea, diarrhoea) at the high doses. For comprehensive glutathione and connective tissue support, NAC pairs well with the selenium (which is a cofactor for the glutathione peroxidase and which is essential for the detoxification of the hydrogen peroxide and the lipid peroxides), with the vitamin E (which works in concert with the glutathione for the lipid antioxidant defence), with the alpha-lipoic acid (which is another antioxidant that helps to regenerate the glutathione and which works through a complementary mechanism), and with the glycine and the glutamate (which are the other two amino acids in the glutathione tripeptide and which should be taken together with the NAC for the maximum glutathione-boosting effect).
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