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Phenol-sulfotransferase (PST)

 

This speaks of a condition that affects approximately 80% of the children with autism. It is vital that you understand the symptoms, and if they affect your child, you must “unload the donkey”. PST is a Phase II enzyme that detoxifies leftover hormones (amines) and a wide variety of toxic molecules, such as phenols that are produced in the body (and even in the gut by bacteria, yeast, and other fungi) as well as food dyes and chemicals. These PST reactions include the clearing of bilirubin and biliverdin, which are the breakdown products of hemoglobin. A high reading could indicate possible PST deficiency. Yellow eyes or skin might be apparent. Low CO2, low glucose, and high bilirubin are also indications of low thyroid function. In children, a low thyroid condition often is not apparent in the blood. The high bilirubin interferes with the clearance of thyroid hormones from the blood; so, the blood will look normal, but there aren’t enough thyroid hormones available to the cells.

 

There are many varieties of phenols. This may indicate why children’s intolerances vary. Remember, Bolte notes that tetanus infection of the intestines leads to the formation of toxic phenols, and states that these are particularly formed by overgrowth of the Clostridium family of bacteria. The toxins formed can peel the lining of the colon right off the organ, and lead to an explosive, debilitating form of diarrhea. She notes that tetanus also attacks the Purkinje cells of the brain potentially reducing the production of the amino acid GABA, a calming neurotransmitter known to affect speech.

 

“The PST enzyme is only one of many sulfotransferases, and various other body chemicals can increase the quantity of some sulfotransferases, and that would increase their activity....Sulfate must be grabbed by any sulfotransferase before the enzyme can attach it to something else, like phenols or MHPG (3 methoxy-4-hydroxyphenylglycol, a natural breakdown product of a class of neurotransmitters called catecholamines). If the PST enzyme activity towards something is low, you can boost it by two approaches. The first is to increase the amount of sulfate available to it. The second is to increase the amount of the enzyme so it has an easier job finding the available sulfate.”—Susan Owens.

 

The PST enzyme links an oxidized sulfur molecule (a sulfate) to these various toxic substances to solubilize them so the kidneys can dispose of them. Obviously, if sulfate is low or missing, this can’t happen effectively. Hence, the problem can be twofold: there may be a lack of phenol-sulfotransferase enzymes, or of the sulfates (due to the absence of protein and of sulfur carrying raw vegetables in the diet, the poor absorption of sulfur from the diet, a failure to metabolize sulfur into sulfate form, or increased urinary excretion of sulfite and sulfate), or both. These deficiencies cause sulfate levels in PST children to be about 15% of NT kids! The sulfates are easily inhibited by flavonoids (Quercetin in particular) and foods that provide neurotransmitters that then must be subsequently metabolized with sulfate (cheese, banana, chocolate), and by foods that inhibit PST enzymes (citrus fruits).

 

Dr. Rosemary Waring’s research shows that the lack of sulfate is the primary problem in 73% of these children (another study found low levels in 92%), but all of those Waring checked had a low PST level too.  “Patients with well defined reactions to foods were examined for their ability to carry out both sulphur and carbon oxidation reactions. The proportion of poor sulphoxidisers (58 of 74 or 78%) was significantly greater than that of a previously determined normal control population (67 of 200 or 33%). Metabolic defects may play a part in the pathogenesis of adverse reactions to foods.”—Poor Sulphoxidation Ability in Patients with Food Sensitivity, Scadding GK et al., British Medical Journal, 1988 Jul 9; 297 (6641): 105-7. Similar sulfate deficiencies have been reported in people with migraine, rheumatoid arthritis, jaundice, and other allergic conditions all of which are anecdotally reported as common in the families of people with autism. Adequate sulfoxidation requires adequate supplies of B-vitamins, especially vitamin B6. The PST enzymes are inhibited or overloaded by chocolate, bananas, orange juice, vanillin, and food colorants such as tartrazine. Removal of these from the diet and supplementation of sulfates may well relieve all these symptoms. The lack of sulfation could well be due to the largely carbohydrate diet of most of these children. It is likely a combination of all these things. In any case, toxic compounds of these aforementioned chemicals can build to dangerous levels. A high value for the tIAG as well as a high reading for DHPPA (rather HPHPA—a phenolic metabolite of tyrosine) both indicate a PST problem.

 

There are two pathways by which the Phase II enzymes process these toxins. One attaches the sulfates as mentioned, and the other attaches glucuronide. Unfortunately, beta-glucuronidase, an enzyme produced by intestinal bacteria, reverses the glucuronidation reaction and releases previously conjugated toxins to be reabsorbed from the intestine, resulting in increased toxicity. One can improve the glucuronic pathway by eating cruciferous vegetables, grapefruit, apples, and oranges, or by supplementing Phyt-AloeR (by MannatechTM) or Calcium D-Glucarate (now being proven a powerful cancer preventive and treatment aid) that inhibits the action of this enzyme by 50%.

 

Dr. Waring has found that in autistic patients there is not nearly enough sulfate to glucuronate ratio. She and her associates feel that the “leaky gut”, that causes a need for a Gf/Cf diet, is caused by this lack of adequate sulfate to provide sulfation of the glucosaminoglycans (sulfated sugars). They found that the glucosaminoglycans (GAGs) in the gut were very under sulfated, and that this causes a thickening of the basement membrane of the gut. IGF (insulin-like growth factor) is important for cell growth. IGF-1 (which is reduced in zinc deficiency) increases the incorporation of sulfate in glucosaminoglycans. Individuals who have poor sulfation in the gut allow polar xenobiotics to freely enter the circulation. They then go to the liver for cytochrome p450 and glutathione detoxification. These excess xenobiotics, dysbiosis, and allergies overwhelm the detoxification pathways and deplete vital stores of antioxidants compromising the health totally.  I’ll mention that IGF-1 is also needed to enhance stem cell activity and to repair muscles, and stem cell production is enhanced four-fold by Ambrotose (Mannatech, Inc). IGF-1 is plentifully supplied by Colostrum.

 

Unfortunatelefy, a lack of sulfated GAGs in the kidneys will allow loss of these sulfates. There is often found low plasma sulfate and high urine sulfate and high urinary thiosulfate as if the kidneys are not able to retain (recycle) sulfate. This needed retention requires the work of a transporter that has been found in “in vitro” studies to be blocked almost completely by mercury and by excess chromium (but not as thoroughly). One study found urinary sulfite to be elevated due to a lack of molybdenum in 36%. Supplementing moly showed improvements in clinical symptoms. When supplementing sulfur or sulfates, as in Epsom salts baths, molybdenum is being lost and must be supplemented. Sugar increases the amounts of calcium, oxalate, uric acid, and glucosaminoglycans being wasted in the urine.

 

Sulfates have a negative charge and repel each other, so that charge forms a barrier on the outside of the cell called the matrix, or the glycocalyx. Sulfate is often found in the glycoprotein film also, usually attached to the essential saccharides Galactose, N-acetylgalactosamine, and N-acetylglucosamine. Glycoprotein is a sugar-protein film that enables cell-cell communication. This film is on all cells of the body, so if systemic sulfate is low, you  most likely have a big problem that is quite general to the whole body. Specifically, the more densely sulfated the GAGs, the more they can resist all kinds of infection. These sulfate molecules govern or influence the ability of the cell to produce its unique set of specialized proteins. It is not something you want to be operating from a deficit, yet that is the condition of most autistic children especially those we call PST deficient. This lack of sulfates may well block the effects of the glycoprotein supplements such as Ambrotose®.

 

Dr. Waring found that 92% of autistic children seem to be wasting sulfate in the urine, for blood plasma levels are typically low and urinary levels are high. There is also an abnormal cysteine to sulfate ratio. In the aged and in chronic disease, methionine is not efficiently converted to cysteine, but builds homocysteine, an intermediate between methionine and cysteine. This can create a deficiency of this vital amino acid, cysteine, and a lack of sulfate. Cysteine is the amino acid that should metabolized to sulfate, so it appears that the sulfate is probably being utilized far faster than the cysteine can be converted, leaving a deficit of sulfate (sugar wastes it), or the cysteine is not being metabolized to sulfate (cytokines hinder it). That may cause the cysteine to build up to toxic levels. Homocysteine and cysteine are powerful excitotoxins. A deficiency of cysteine, or a failure to metabolized it to sulfate, will produce multiple chemical sensitivities and food allergies. Being a major part of the powerful antioxidants alpha lipoic acid and glutathione, a deficiency of cysteine, or a failure to metabolize it into these antioxidants, would greatly affect the liver’s ability to detoxify, and would lead to destruction throughout the body by free radicals This would also allow buildup of the heavy metals lead, cadmium, mercury, and aluminum. Supplementation of vitamin B2, B6, B12, folic acid, magnesium, and TMG may normalize metabolism of methionine into cysteine, but vitamin C is needed to prevent cysteine (which contributes its sulfur more readily) from converting to cystine, its oxidized form.

 

What could be interfering with sulfation? Primarily, mercury, but Hepatitis B vaccine was found to inhibit sulfation chemistry for at least one week in typical people. When tumor necrosis factor alpha (TNF-a) is elevated (frequently in autism), it can inhibit the conversion of cysteine to sulfate. A methylation defect, when present, can cause a defect in sulfation. Another is swimming! High concentrations of chlorate were detected in samples from a number of pools; in one case as high as 40 mg/l. Higher chlorate concentrations were associated with those pools using the oxidant hypochlorite solution as a disinfecting agent, while relatively low chlorate concentrations were found in pools treated with gaseous chlorine. Chlorate IS the biological substance of choice to block sulfation. Additionally, chlorate is known to inhibit hematopoiesis [the making of new blood cells], a problem with many of our kids. Additionally, hypochlorite reportedly combines with any phenolic compound, even in very dilute solutions, to form an aromatic compound that can react in the body. This combining of chemicals can be very toxic to susceptible individuals. One Mom found that an Epsom salts bath immediately following eliminated after-swimming problems in behavior. So, if you must swim, do the bath immediately after coming from the pool. For home pools, one Mother reports, “An ionizer cuts down chlorine use by 70-80%. Since installing this, we don’t see the reactions anymore.”

 

Cysteine is one of the sulfur containing amino acids. It can be manufactured in the body from two other amino acids, serine and methionine. When a critical enzyme, cysteine oxidase, used in metabolizing L-cysteine, is deficient, an abnormal metabolite of L-cysteine, called cysteine-S-sulfate, accumulates in the nervous system. This may cause the same pattern of neuron destruction seen with high doses of glutamate or MSG. Dr. John Olney and others found that when L-cysteine is given orally to mice in large doses it produced a pattern of brain damage identical to that of excess glutamate.

 

The excess-cysteine/low-sulfate condition that Waring observed may be because of a deficiency of the amino acid histidine that can be run low by seasonal allergies and the medications taken to treat them. Metal toxicities, common in these kids, can run it low. Experimental deficiency of histidine causes an excess of free iron in the blood producing free radicals that must be neutralized by a good antioxidant. This deficiency can adversely affect the enzyme cysteine dioxygenase (CDO), the essential nutritional components of the enzyme being histidine and iron. A deficiency of this amino acid, possibly caused by allergies, heavy metals poisoning, and medications, not only affects HCl production (histidine delivers zinc to the cells, and together they produce HCl), but it will likely cause a toxic build up of the amino acid cysteine, and a lack of sufficient taurine and sulfate contributing to the PST problem. High histidine lowers zinc and copper by chelating them from the body, so supplementing histidine, though needed, may be dangerous without testing to ensure no new deficiencies are created. Supplementing taurine, the sulfur containing amino acid that is at the end of the metabolic chain, has been helpful in meeting this need for taurine; and, being the immediate precursor, may supply needed sulfates. Taurine is reported to have an anti-opioid effect (Braverman 1987). You must support the sulfation pathway and supplement sulfates.

 

The CDO problem is much more likely caused by inadequate kidney clearance of the hormone glucagon than any other reason I have found. Glucagon is insulin’s alter ego and acts like a switch to turn CDO off.  When we eat, glucagon is supposed to clear the blood and insulin is secreted, CDO is enabled and excess cysteine is rapidly catabolized. When we fast, insulin clears and glucagon is secreted. CDO is turned off preserving available free cysteine levels for the body to use as needed. When glucagon doesn’t rapidly clear as it is supposed to, it continues to turn off CDO even after eating, resulting in toxic, free-cysteine levels. The kidney location where glucagon is cleared is also the place in that organ where most pollution and damage occurs from mercury—the brush border lining of the proximal end of the kidney tubule — Jeff Clark, www.cfsn.com. This is another reason to eat according to the glycemic index of foods, and to avoid a high carbohydrate meal.


 

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