Julia Littlewood

Platelet phenolsulphotransferase deficiency in dietary migraine.

Patients with dietary migraine were found to have significantly lower levels of platelet phenolsulphotransferase activity than either migrainous patients without a history of dietary provocation or normal controls. Of the two known human variants of this enzyme, the phenol-inactivating P form, for which no endogenous substrate has so far been identified, was more severely involved than the M enzyme, which inactivates monoamines (including tyramine). Such commonly implicated dietary triggering agents as chocolate and cheese may contain as-yet-unidentified phenolic substrates of phenolsulphotransferase P; if the platelet enzyme deficiency were mirrored by low gut activity, abnormally large amounts of potentially toxic substances might gain access to the circulation in consequence.

The prevalence of diet-induced migraine.

Nineteen percent of about 490 patients with classical or common migraine reported that headaches can be precipitated by chocolate, 18% by cheese and 11% by citrus fruit. and a highly significant majority of these patients were sensitive to all three foods. Twenty-nine percent of the patients reported sensitivity to alcohol; again this was significantly associated with sensitivity to the three food stuffs, though a substantial number of patients were sensitive to alcohol but not foods. Thirty-one percent of 331 female patients believed that oral contraceptives precipitated headaches, but this could not be related to any dietary response. Patients with affected relatives were significantly more likely to report sensitivity to alcohol and chocolate; sensitivity to cheese and citrus fruit was less strongly related, and there was no relationship at all for oral contraceptives. These correlations suggest that food induced headaches are mediated by chemical constituents common to these foods.

Low platelet monoamine oxidase activity in headache: no correlation with phenolsulphotransferase, succinate dehydrogenase, platelet preparation method or smoking.

Platelet monoamine oxidase activity in male migrainous and cluster headache patients was significantly lower than in male controls, confirming our previous study. The activity range showed a normal distribution and low mean values could not be attributed to a subgroup with particularly low activity. When Corash s platelet preparation method was used, with its high platelet yield, specific enzyme activities of a similar order were obtained. Thus, the low values encountered were not due to abnormal recovery within the platelet population. Two other enzyme activities, phenolsulphotransferase M and succinate dehydrogenase, were also measured in the same platelet samples. Although low succinate dehydrogenase activity was identified in the headache groups, it appeared to represent a separate phenomenon and there was no significant correlation between activity of either enzyme and that of monoamine oxidase. This shows that the low activity of platelet monoamine oxidase in headache is not related to a generalised platelet enzyme deficit. It was also shown that the low monoamine oxidase activity in the headache patients could not be attributed to smoking.

Migraine and cluster headache: links between platelet monoamine oxidase activity, smoking and personality.

SYNOPSIS

Platelet monoamine oxidase: specific activity and turnover number in headache

Monoamine oxidase turnover numbers (molecules of substrate converted to product per minute per active site) have been calculated for the human platelet enzyme using [3H]pargyline. Headache patients with high and low monoamine oxidase specific activities relative to controls were found to have turnover numbers very close to those for controls. This finding suggests that their specific activities vary because of differences in the concentration of active monoamine oxidase molecules, rather than differences in the ability of those enzyme molecules to catalyse the deamination reaction.

Biochemical Predisposition to Dietary Migraine: the Role of Phenolsulphotransferase

SYNOPSIS

Psychiatric morbidity, platelet monoamine oxidase and tribulin output in headache

A significantly higher proportion of patients with headache showed scores in the psychopathological range of the General Health Questionnaire (GHQ) compared with controls, with ratings particularly high on the anxiety and depression subscales. Across the whole group, there was a significant negative correlation between platelet monoamine oxidase (MAO) activity and GHQ score overall, and with the anxiety and depression subscales. There was a significant positive correlation between platelet MAO activity and urinary output of the endogenous MAO inhibitor, tribulin. Within the migraine group, there was a significant negative correlation between tribulin output and GHQ score. These findings suggest that the biochemical nature of the anxiety associated with migraine may differ from that in other conditions such as generalized anxiety disorder where high platelet MAO activity and high tribulin output have been reported.

Thromboxane synthetase inhibition: potential therapy in migraine

SYNOPSIS

Clinical Studies on Platelet Phenolsulphotransferase

As pointed out in the Introduction (Sandler, this volume), the identification of phenolsulphotransferase (PST) in the human platelet has given us, potentially at least, another reflection of events in the rest of the body, possibly including the brain. And with the identification of multiple forms of this enzyme, as desscribed by Rein et al. (this volume), the possibility of obtaining useful clinical information has been greatly increased.

Phenolsulphotransferase and its clinical importance

The sulphotransferases are a large group of enzymes which transfer sulphate to a broad variety of different substrates, acting by the same general mechanism. Phenolsulphotransferase (PST; EC.2.8.2.1) (Gregory and Lipmann, 1957) is typical of this group in that it catalyzes the transfer of sulphate from a donor, 3’-phosphoadenosine 5’-phosphosulphate (PAPS), so called “active sulphate”, to a wide range of phenols.