Cysteine (C, Cys)

Cysteine:

    • Cysteine is named after cysteine, which comes from the Greek word kustis meaning bladder-cystine was first isolated from kidney stones.
    • Cysteine is a naturally occurring, sulfur-containing amino acid that is found in most proteins, although only in small quantities.
    • It serves two biological functions: a site of redox reactions and a mechanical linkage that is involved in protein folding to retain their three-dimensional structure and link to one another.
    • Due to this ability to undergo redox reactions, cysteine has antioxidant properties.
    • Cysteine is often involved in energy metabolism, electron-transfer reactions, and help the enzyme catalyze its reaction

Metals:

    • Cysteine is part of the metabolism of different metals in the body including iron, zinc, and copper.
    • Cysteine can remove heavy metal toxins from the body, including mercury, cadmium, lead, and arsenic.
    • Cysteine also enhances the effect of topically applied silver, tin and zinc salts in preventing dental cavities.
    • In the future, cysteine may play a role in the treatment of cobalt toxicity, diabetes, psychosis, cancer, and seizures.

Needed to:

    • Make Taurine.

Metabolism:

    • Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces. Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease, and cardiovascular disease.

Uses/Sources:

    • For the prevention of liver damage and kidney damage associated with overdoses of acetaminophen.
    • Cysteine is found in eggs and sesame in high concentrations, as well as in many other foods.

Health Effects:

    • Cysteine has clinical uses ranging from baldness to psoriasis to preventing smoker's hack. In some cases, oral cysteine therapy has proved excellent for treatment of asthmatics, enabling them to stop theophylline and other medications.

The Heart and Cells:

    • Methionine is an intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and other phospholipids. Improper conversion of methionine can lead to atherosclerosis.
    • Methionine and other methyl donors including cysteine, choline, and cofactors such as vitamin B6 were significantly reduced in Lupus/SLE patients compared to healthy matched controls.
    • The RDA for methionine (combined with cysteine) for adults has been set at 14 mg/Kg of body weight per day. Therefore a person weighing 70 Kg, independent of age or sex, requires the consumption of around 1.1 g of methionine/cysteine per day. The WHO recommendations for methionine/cysteine intake of 13 mg/kg of body weight are in the same range as those suggested by the RDA. Intake of methionine/cysteine measured in 32 individuals ranged between 1.8 and 6.0 g/day (14 and 45 mmol/day).

Symptoms:

    • Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur.
    • Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome.
    • Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.

Treatment:

    • Kidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.
    • Lipoic acid would need to be supplemented in pill form for this purpose.
    • Garlic might be useful because of its thiols.

Route of Exposure:

    • Endogenous, Ingestion, Dermal (contact)

Cautions:

    • High doses can cause kidney stones in people with cystinuria, it can inactivate insulin, use caution if you have diabetes.
    • Taking this can deplete zinc and copper, if using this or n-acetylcysteine for more than a few weeks, take it with a multi-vitamin/mineral supplement that has a daily value of these minerals.

Cystine:

  • is a structural component of many tissues and hormones. is the oxidized dimer form of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is slightly soluble in water.

N-acetylcysteine:

    • NAC (N-Acetyl Cysteine) is a supplement that can increase cysteine. Cysteine has been used to stimulate the synthesis of another amino acid, glutathione. May also combat the side effects of chemotherapy, radiation therapy and clear mucus from lungs of smokers.
    • Glutathione S-transferases enzymes: Cysteine is also part of the antioxidant glutathione. N-acetyl-L-cysteine (NAC) is a form of cysteine where an acetyl group is attached to cysteine's nitrogen atom and is sold as a dietary supplement.
    • Supplement recommendations for antioxidants: nutrients are critical for increasing glutathione synthesis:NAC (N-Acetyl Cysteine) 20 mg
    • Unless the cause of your bad breath is obvious, focus first on your diet and take supplements to improve your digestion, probiotics, betaine HCL, and digestive enzymes. In addition, take 500 to 1,000 mg of N-acetyl cysteine daily and 250 mg of milk thistle twice daily for 28 days to detox your liver.

Cystathionine-gamma-ligase (CTH):

    • Is an enzyme which converts cystathionine into cysteine, the second step of the transsulfuration pathway which is encoded for by the CTH gene.

Methionine (in the form of SAM-e) and Cysteine (in the form of NAC):

    • Methionine converts to cysteine, so supplementing with cysteine reduces the requirements for methionine.
    • Cysteine and methionine are not stored in the body.
    • When you have a deficiency in sulfur amino acids such as methionine, glutathione levels suffer more than more critical processes such as protein synthesis.

Methionine Is Often Found In The Same Foods With Cysteine:

    • There is some evidence that dietary methionine (and cysteine) is important to ensure the health of the intestine and immune function during development and in inflammatory states.
    • Relative to healthy piglets fed a deficient diet, piglets supplemented with cysteine (0.25 g/kg) and methionine (25 g/kg) had less intestinal oxidative stress, improved villus height and area and crypt depth, and a higher number of goblet cells.
    • In order to increase growth, chicken diets are always supplemented with methionine/cysteine.
    • Foods containing methionine are transformed into homocysteine in the bloodstream. Homocysteine is converted in the body to cysteine, with vitamin B6 facilitating this reaction. Homocysteine can also be recycled back into methionine using vitamin B12-related enzymes.

Cysteine Is A Uremic Toxin:

Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics:

1) small, water-soluble, non-protein-bound compounds, such as urea;

2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and

3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.

    • Uremic toxins such as cysteine are actively transported into the kidneys via organic ion transporters (especially OAT3).
    • Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart).
    • Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species.
    • Although classified as a non-essential amino acid cysteine may be essential for infants, the elderly, and individuals with certain metabolic disease or who suffer from malabsorption syndromes.
    • Cysteine can usually be synthesized by the human body under normal physiological conditions if a sufficient quantity of methionine is available.
    • Due to the ability of thiols to undergo redox reactions, cysteine has antioxidant properties.
    • Cysteine's antioxidant properties are typically expressed in the tripeptide glutathione, which occurs in humans as well as other organisms.
    • The systemic availability of oral glutathione (GSH) is negligible; so it must be biosynthesized from its constituent amino acids, cysteine, glycine, and glutamic acid.
    • Glutamic acid and glycine are readily available in the diets of most industrialized countries, but the availability of cysteine can be the limiting substrate.
    • Cysteine is also an important source of sulfide in human metabolism. The sulfide in iron-sulfur clusters and in nitrogenase is extracted from cysteine, which is converted to alanine in the process.
    • In a 1994 report released by five top cigarette companies, cysteine is one of the 599 additives to cigarettes. Its use or purpose, however, is unknown, like most cigarette additives. Its inclusion in cigarettes could offer two benefits: Acting as an expectorant, since smoking increases mucus production in the lungs; and increasing the beneficial antioxidant glutathione (which is diminished in smokers).

Homocysteine:

    • (check annually)
      • Homocysteine levels are often low with CBS upregulated due to rapid conversion to taurine, leading to higher levels of ammonia and taurine.
      • Homocysteine levels are often high with CBS downregulated. Higher levels of homocysteine usually lead to low hydrogen sulfide with high blood pressure and low cysteine and B6 levels.
    • The amino acids methionine, taurine, and cysteine all contain sulfur; they are concentrated in animal protein (thus the restriction on animal protein intake).
    • Many nutritional supplements (MSM, N-acetyl cysteine, glutathione) that are good for most people are a problem for those with sulfur problems. While certain aspects of your health will benefit from these agents, they will add to your sulfate/sulfite overload problem, adversely affecting the Methyl Cycle Defect that is the common denominator to all of your health problems.
    • Many people are treated using high doses of vitamin B6 (also known as pyridoxine). Slightly less than 50% respond to this treatment and need to take supplemental vitamin B6 for the rest of their lives.
    • Those who do not respond require a Low-sulfur diet (especially monitoring methionine), and most will need treatment with trimethylglycine.
    • A normal dose of folic acid supplement and occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine (so adding cysteine can be important to reduce oxidative stress).
    • If you have elevated cysteine and you want to convert some to glutathione, take a 2:1 weight ratio of glutamine and glycine (2-500 mg caps of glutamine with 1-500 mg cap of glycine) and your body will do the rest.
    • If homocysteine cannot be converted into cysteine or returned to the methionine form, levels of homocysteine in the body increase. Elevated homocysteine levels have been associated with heart attack, stroke, blood clot formation, and perhaps the development of Alzheimer's disease.

Low Cysteine:

    • If Cysteine levels are low due to oxidative stress then there is usually a reduction in glutathione.
    • Cysteine will usually be low with high homocysteine levels.

Causes of Low Homocysteine and How to Increase It:

Low protein intake:

    • You need to make sure you are eating adequate protein. Approximately 1 gram per 2 pounds of body weight is a rough guideline.

Low sulfur intake:

    • Not consuming enough sulfur-containing foods, homocysteine will break down in order to provide much-needed cysteine for the body.
    • Cysteine is very important for many reactions. If cysteine levels are low, the body will break down glutathione in order to provide it! So not only does one become low in homocysteine, but also glutathione.
    • Eating your cruciferous vegetables is very important as they contain sulfur.
    • You can also support with MSM or NAC.
    • If you don’t do well with sulfur-containing vegetables or other foods – or sulfur-containing supplements, then you may have a molybdenum deficiency for various reasons. Molybdenum is the mineral needed to break down sulfites. Consider taking a molybdenum supplement and also determine why you need to.

AdoHcy hydrolysis:

    • Serves not only to sustain the flux of methionine sulfur toward cysteine but is believed also to play a critical role in the regulation of biologic methylations.

Sulfur/Thiol:

    • Plasma cysteine status is either low, normal or high and will indicate if someone will tolerate high sulfur (thiol) foods or supplements. 33-50% of mercury toxic people have elevated plasma cysteine. This has nothing to do with plasma sulfate (SO4) status or liver sulfation status. Plasma sulfate status can be independently low, normal or high.
    • It is possible for cysteine status to change as chelation progresses. When planning to chelate you should do a sulfur exclusion trial at least once to determine if there is a sensitivity to sulphur foods and avoid a lot of suffering.
    • Sulfur foods and supplements are those containing a thiol group (like coffee and chocolate). NAC is an example of a thiol supplement.
    • The negative effects of sulfur on high cysteine people may occur over a 4-7 day period after the last sulfur ingestion. It is advised to do a 7-day exclusion with no ALA chelation during sulfur exclusion.
    • Sulfur food intolerance in mercury toxic people has more to do with the mobilization of mercury caused by raised cysteine levels and excess thiols, rather than a direct allergy or intolerance to sulfur foods. Avoid them if you show an intolerance to them, or, as some people have found, keep them to an absolute minimum.
    • Cysteine is unique amongst the twenty natural amino acids as it contains a thiol group.
    • L-Cysteine is a precursor of the thio ethanolamine portion of coenzyme A and of the taurine that conjugates with bile acids such as taurocholic acid.
    • Thiol groups can undergo oxidation/reduction (redox) reactions; when cysteine is oxidized it can form cystine, which is two cysteine residues joined by a disulfide bond. This reaction is reversible: as the reduction of this disulphide bond regenerates two cysteine molecules. The disulphide bonds of cystine are crucial to defining the structures of many proteins.
    • Oxidation of cysteine can produce a disulfide bond with another thiol, or further oxidation can produce sulphuric or sulfonic acids.
    • The cysteine thiol group is also a nucleophile and can undergo addition and substitution reactions.
    • Thiol groups become much more reactive when they are ionized, and cysteine residues in proteins have pKa values close to neutrality, so are often in their reactive thiolate form in the cell.
    • The thiol group also has a high affinity for heavy metals and proteins containing cysteine will bind metals such as mercury, lead and cadmium tightly.
    • Cysteine is an important source of sulfur in human metabolism, and although it is classified as a non-essential amino acid, cysteine may be essential for infants, the elderly, and individuals with certain metabolic disease or who suffer from malabsorption syndromes.

Hyperhomocysteinemia and the genetic condition, homocystinuria:

  • Elevated levels of homocysteine are implicated in both cancer and cardiovascular disease. In these regards, one mechanism that may exist for lowering elevated levels of homocysteine in some individuals is taking supplemental NAC (n-acetyl cysteine). NAC is the precursor of glutathione.

Glutathione:

    • Is a tri-peptide, consisting of 3 amino acids: glutamine, glycine, and cysteine.
    • Cysteine is also part of the antioxidant glutathione. N-acetyl-L-cysteine (NAC) is a form of cysteine where an acetyl group is attached to cysteine's nitrogen atom and is sold as a dietary supplement.

Metallothioneins (MTs):

    • Are cysteine-rich, small metal-binding proteins.

Hydrogen Peroxide:

    • You can scavenge hydrogen peroxide directly with lipoic acid and cysteine.
    • We may not have enough since the world we live in might place a higher burden on cysteine to detox toxins.

Genes Involved:

    • MAPK1
    • MAPK3
    • AS3MT
    • MAPK8
    • ABCC2
    • CTH
    • TNF
    • MPO
    • CD86
    • LPO
    • PDGFRB
    • RELA
    • ACTA2
    • MMP2
    • SLC22A4
    • ACTA2
    • SLC2A1
    • SOD2
    • PDGFB
    • SLC22A5
    • HMOX1
    • TGFB1
    • CDO1
    • SLC7A5
    • TGFB2
    • NFKBIA
    • ADORA1
    • GSTA3
    • CAT
    • KIF5A
    • AKT1
    • COL1A1
    • CYP1A1
    • ICAM1
    • TIMP2
    • NOS2
    • COL2A1
    • TXNRD1
    • CSAD
    • RB1
    • TGFBR2
    • GSTM1
    • GSTA2
    • CCND1
    • SLC3A1
    • GSTP1
    • SLC6A19
    • CDKN1B

CBS:

Activates the sulfuration process, the biosynthesis of the sulfur-containing amino acid cysteine, and the fate of residual sulfur byproducts through various downstream processes.

SNP’s Involved:

    • rs1145920 CTH A11886G A
    • rs515064 CTH A32114G G
    • rs663649 CTH G25229T T
    • rs10889869 CTH G6010A A
    • rs1021737 CTH S4031I T
    • rs12723350 CTH T16147C C
    • rs681475 CTH T8763C C

Health Effects:

    • Anti Addisonian
    • Antibiotic
    • Anti cataract
    • Anti cytotoxic
    • Anti ophthalmic
    • Antioxidant
    • Antitumor
    • Anti ulcer
    • Cancer preventive
    • Detoxicant
    • Glutathionergic
    • Ophthalmic anti alkali
    • Pesticide

Disease Inference:

    • Liver Cirrhosis, Experimental 51.09
    • Lung Neoplasms 42.16
    • Diabetes Mellitus, Experimental 41.75
    • Alcoholic liver cirrhosis 41.73
    • Diabetes Mellitus, Type 2 40.78
    • Brain Ischemia 35.99
    • Hepatocellular carcinoma 35.84
    • Breast carcinoma 33.53
    • Reperfusion Injury 30.07
    • Prostatic Neoplasms 29.84
    • Hypertension 28.76
    • Calcinosis 27.62
    • Marfan Syndrome 26.94
    • Kidney Neoplasms 26.58
    • Neoplasm Invasiveness 26.42
    • Colonic neoplasm 26.35
    • Colorectal cancer 26.03
    • Myocardial infarction 26.0
    • Myocardial Ischemia 25.09
    • Oral Submucous Fibrosis 25.06
    • Radiation Injuries, Experimental 25.04
    • Neoplasm Metastasis 24.85
    • Trigeminal Neuralgia 23.04
    • Inflammation 21.62
    • Thoracic aortic aneurysm 21.44
    • Asthma 21.21
    • Pulmonary Fibrosis 21.21
    • Rheumatoid arthritis 20.98
    • Cell Transformation, Neoplastic 20.61
    • Stomach Neoplasms 20.21
    • Pulmonary Emphysema 19.41
    • Squamous cell carcinoma 19.07
    • Disease Models, Animal 18.88
    • Fibrosis 18.35
    • Psoriasis 18.34
    • Precancerous Conditions 18.0
    • Ischemia 17.86
    • Retinal Diseases 17.13
    • Aortic Valve Insufficiency 17.12
    • Dermatitis, Contact 17.04
    • Chronic obstructive pulmonary disease 16.99
    • Plasmodium Falciparum Blood Infection Level 16.99
    • Carcinoma 16.92
    • Urinary Bladder Neoplasms 16.9
    • Mesothelioma 16.63
    • Cardiomyopathies 16.56
    • Turner Syndrome 16.49
    • Ovarian Neoplasms 15.35
    • Mesothelioma, Malignant 15.24
    • Wounds and Injuries 14.99
    • Colitis 14.95
    • Sepsis 14.91
    • Status Epilepticus 14.75
    • Occupational Diseases 14.45
    • Kidney Failure, Chronic 14.34
    • Liver Neoplasms 14.31
    • Brain Neoplasms 13.52
    • Focal segmental glomerulosclerosis 13.23
    • Drug-induced liver injury 13.17
    • Renal cell carcinoma 13.1
    • Carcinoma, Non-Small-Cell Lung 12.97
    • Shock, Hemorrhagic 12.87
    • Cholestasis 12.84
    • Autoimmune disease 12.8
    • Burns 12.6
    • Sezary Syndrome 12.58
    • Esophageal squamous cell carcinoma 12.56
    • Nasopharyngeal carcinoma 12.56
    • Pancreatic carcinoma 12.5
    • Osteoporosis, Postmenopausal 12.46
    • Atherosclerosis 12.13
    • Ulcerative colitis 12.02
    • Urticaria 11.93
    • Aortic Diseases 11.77
    • Parkinson's disease 11.77
    • Furlong syndrome 11.54
    • Cholangitis 11.53
    • Cardiac hypertrophy 11.5
    • Hyperplasia 11.43
    • Diabetic nephropathy 11.17
    • Arthritis, Experimental 11.15
    • Esophageal Neoplasms 11.06
    • Obesity 11.05
    • Amphetamine-Related Disorders 10.96
    • Osteoarthritis 10.94
    • Drug Hypersensitivity 10.89
    • Hepatitis, Chronic 10.89
    • Adenocarcinoma 10.79
    • Neoplasms, Experimental 10.78
    • Hyperalgesia 10.57
    • Carcinoma, squamous cell of head and neck 10.54
    • Abortion, Spontaneous 10.48
    • Hernia, Diaphragmatic 10.42
    • Disease Progression 10.39
    • Myocardial Reperfusion Injury 10.19
    • Diabetic Neuropathies 10.17
    • Liver Diseases 10.13
    • Lung Diseases 10.04
    • Nephrogenic Fibrosing Dermopathy 10.04
    • Malaria 10.01