What Is Sulfation?
Sulfation is a process where sulfate molecules are added to different endogenous (produced internally in the body) and exogenous (consumed from outside) substances. Sulfation is one of the essential processes of Phase 2 detoxification.
Sulfation happens with the help of the Sulfotransferase enzymes (SULTs). This reaction was first identified in 1876 when a scientist detected phenyl sulfate in the urine of a person who consumed phenol.
The SULTs transfer sulfonate (SO3 –) from the 3‘–phosphoadenosine 5‘–phosphosulfate (PAPS) coenzyme and add them to the hydroxyl or amino group elements that need to be detoxified.
There are two groups of SULT enzymes.
Membrane-bound SULTs - They primarily help metabolize endogenous hormones, neurotransmitters, peptides, and lipids. The enzymes are present in the Golgi apparatus (a subunit within the cells)
Cytosolic SULTs - These are present in the cytosol (a liquid component found inside cells) and help regulate endogenous and exogenous substances.
Importance Of Sulfation
Sulfation helps in clearing many phenolic drugs (drugs derived from plants), hormones, neurotransmitters, and environmental toxins.
SULTs metabolize the following endogenous substances.
- Steroids
- Eicosanoids (signaling molecules)
- Serotonin (a mood-altering chemical that improves sleep)
- Catecholamines (a type of neurotransmitter)
- Iodothyronines (enzymes that control thyroid hormone activity)
- 6-hydroxymelatonin (a naturally occurring metabolite of melatonin)
- Vitamins like retinol (vitamin A derivative) and vitamin D
- Bile acids
- Peptides
- Lipids
SULTs also play a role in converting major procarcinogens (cancer-causing agents) into their more active form before the body eliminates them.
Most of the detoxifying enzymes are expressed only in adulthood and are not found in early life. SULTs are different in that way. Studies show that SULTs may help in detoxification in the liver of fetuses as early as 20 weeks of pregnancy).
In some cases, adding a sulfate molecule to another molecule makes it more water-soluble and is then quickly eliminated from the body.
SULTs - SULT1A1 (Sulfurtransferases)
There are three kinds of SULT families identified in human beings: SULT1, SULT2, and SULT4. All these, together, produce about 13 different enzymes.
The SULT1A1 enzyme is one of the essential sulfotransferase enzymes and is expressed majorly in the human liver. It is also found in other places like the brain, intestine, platelets, kidneys, and lungs.
SULT1A1 enzyme converts a lot of cancer-causing agents into their more active intermediate forms. These intermediates can cause gene changes (mutations) and an increased risk of cancer.
A 2004 study explored the effects of SULT1A1 gene changes and the risk of breast cancer in Chinese women. The study reports a positive relationship between SULT1A1 gene variations, changes in the SULT1A1 enzyme levels, and breast cancer.
Another meta-analysis analyzed the reports of 20 individual case-control studies that related SULT1A1 gene changes to the risk of breast cancer. This study concluded that the SULT1A1 Arg213His gene variation (genetic polymorphism) can increase the risk of breast cancer, especially in the Asian population.
The C allele homogenous of the SNP rs1042157 of the SULT1A1 gene leads to slow sulfation of phenolic substances and drugs.
Substances That Get Sulfonated
The below are substances that get sulfonated in the body.
- Phenols - Phenols are both naturally occurring and synthetically produced substances. The SULT1A1 enzyme plays a role in the sulfation of phenols in the body.
- Aromatic amines - Aromatic amines are organic compounds that include benzene, naphthalene, purine, toluene, and acridine. Aromatic amines are found in tobacco smoke, hair dyes, fuel exhaust, and many manufacturing plants.
- Benzyl alcohols - Benzyl alcohol is a type of aromatic alcohol. It is very commonly used in the production of paints, inks, lacquers, and anesthetics. The SULT1A1 enzyme is the primary substance that sulfates benzyl alcohol.
- Naphthol - Naphthols are used to produce tanning agents, dyes, and even antiseptics and are carcinogens (cancer-causing agents). The SULT1A1 enzyme sulfates naphthol that enters the body.
- Dopamine - Dopamine is a type of neurotransmitter that sends messages between the body and the brain. Dopamine is called the feel-good hormone. In the human body, the SULT1A3 enzyme converts dopamine to dopamine sulfate.
- Iodothyronines - Iodothyronines are enzymes that activate and deactivate the two thyroid hormones - triiodothyronine (T3) and thyroxine (T4). Studies show that the SULT2A1 enzyme plays an essential role in iodothyronine sulfation along with the SULT1A1 enzyme.
- Aromatic hydroxylamines - Hydroxylamines are chemicals used in various manufacturing processes. The SULT1A2 enzyme can sulfate hydroxylamines and convert them into a more active and toxic intermediate substance that needs to be removed quickly from the body.
Recommendations To Boost Sulfation (SULTs)
Genetic testing
Genetic testing can help understand SULT activity in the body. Some people with changes in the SULT genes may need to get screened for cancers more frequently.
Dietary and substance interaction
Certain kinds of foods and ingredients induce or inhibit SULT activity in the body.
Substances that induce SULT:
- Caffeine (coffee, green tea, black tea, cocoa)
- Retinoic acid-rich foods (liver, eggs, dairy products, and vegetables like fruits like apples, apricots, asparagus, carrots, and artichokes)
Substances that contain dietary sulfur and can boost sulfation:
- Legumes and grains including beans, peas, oatmeal, barley
- Nuts and seeds including almonds, peanuts, walnuts, and brazil nuts
- Ginger
Below is the list of foods and substances that can inhibit sulfation activity. If your SULT enzymes are underactive genetically, then you should restrict or avoid these.
- Citrus juices like grape and orange
- Curcumin (a chemical found in turmeric) inhibits SULT1A1 enzyme activity in the liver
- Flavonoids in vegetables and fruits
- Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) inhibit SULT1A1 activity
Summary
- Sulfation is the addition of sulfate molecules to endogenous and exogenous substances in the body.
- The Sulfotransferase enzymes (SULTs) help in sulfation. Membrane-bound SULTs and cytosolic SULTs are two groups of these enzymes depending on where they are found.
- SULTs can make a substance inactive or water-soluble to help detoxify it. In some cases, it converts a substance into its more active intermediary.
- SULT1A1 is the most important SULT enzyme and is expressed in the liver. Certain changes in the SULT1A1 gene can increase a person’s risk of developing many kinds of cancers.
- Substances like phenols, aromatic amines, benzyl alcohol, naphthol, dopamine, Iodothyronine, and Aromatic hydroxylamine are all sulfated by the SULT enzymes.
- Certain substances like caffeine and retinol can induce SULT activity in the body, and others like citrus fruits, flavonoids, and curcumin can inhibit SULT activity.
- Genetic testing helps identify SULT gene changes in the body. People with low levels of SULT enzymes may have to get screened periodically to identify and bring down the risk of cancers.
