Sulphate metabolism in autism

Normal biochemistry

This is a complex subject in which the sulphate ion can be both produced in the body through biochemical formation (generally from methionine and cysteine aminoacids) and absorbed from the gut.

It is transported across membranes by various transporter protein molecules, which are found almost universally in the body. The ion is activated into PAPS (adenosine 3’-phosphate 5’-sulphatophosphate) which is a donor molecule to cause the sulphation through the formation of an ester.

This causes the formation of highly soluble molecules that are good for urinary or biliary elimination. The body also forms heparans and glycans using PAPS in a complex method.

In the gut sulphate is absorbed in the small intestine through deliberate transporter molecules, about which little is known concerning their regulation. In an adult the whole body inorganic sulphate turnover is represented by the 841 +/- 49 micromol/hr and average urinary inorganic sulphate excretion is around 600 micromol/hr. Following injection of sulphate into the body around 50% is excreted as esters and whole body sulphation accounted for around 27% of inorganic sulphate turnover. Exracellular inorganic sulphate is an important pool for intracellular sulphation.

Sulphate in autism

It should be noted that sulphate, because of its interaction with cysteine and methionine formation must be viewed with the formation of other sulphur containing compounds e.g. glutathione and oxidative stress

Levels of blood sulphate found in autism (not available but considered to be low)
Urinary sulphate (often as esters) found to be relatively high
Involvement with the formation of antioxidant substances i.e. the inadequacy of these compounds e.g. glutathione. See oxidative stress.
Treatment using sulphate

Glycosaminoglycans in autism

We do know that these compounds (like heparin, and chondroitin sulphate, and the glycosaminoglycans that are present in large amounts in the basal membranes of the gut, kidney and skin) may well be modified but the research in this respect is missing from major literature.

formula of heparinetal

Glycosaminoglycans are long chains of sugar molecules with sulphate modification of some of the ester linked elements. They can be variants and vary dramatically in the amount of sulphate depending on the amount of sulphate available when they are being made.

Normal sulphate biology

It is probably a good idea to read through one of these simply to get a grip on how sulphates are formed, taken in from the gut, and excreted. They may also be created through specific biological mechanisms that are altered in ASD.

Markovich D. Physiological role and regulation of mammalian sulfate transporters. Physiological reviews. 2001;81:1499-1533. also see: Cole D, Evrosvski J. The clinical chemistry of inorganic sulfate. Crit Rev Clin Lab Sci 2000 37(4);299-44. Also see: Hoffer LJ et al. Human sulfate kinetics. Am J Physiol Regul Integr Comp Physiol 2005;289;R1372-80.

Hoffer LJ, Hamadeh MJ, Robitaille L, Norwich KH. Human sulfate kinetics. Am J Physiol Regul Integr Comp Physiol. 2005 Nov;289(5):R1372-80. Epub 2005 Jul 28.

Cole DE, Evrovski J. The clinical chemistry of inorganic sulfate. Crit Rev Clin Lab Sci. 2000 Aug;37(4):299-344.

Alterations seen in autism

McFadden SA.Toxicology.

Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways. 1996 Jul 17;111(1-3):43-65. (autism only used as an example in the impaired sulphation of xenobiotic compounds)

Alberti A, Pirrone P, Elia M, Waring RH, Romano C. Sulphation deficit in "low-functioning" autistic children: a pilot study. Biol Psychiatry. 1999 Aug 1;46(3):420-4. (also found low levels of sulphotransferase in platelets and low plasma sulphate).