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Tuesday, October 4, 2011

TMAU mentioned in popular UK fiction drama show 'Doc Martin' last night

Last night Trimethylaminuria was mentioned in a new episode of the popular doctor fiction drama show in the UK, Doc Martin. The series screens at peak evening viewing time on the popular ITV channel. Last nights show (it's first screening), called 'Mother knows best' included a short filler scene where a young man was at the Dr's surgery with a 'fishy smell'. Doc Martin told him he suspected TMAU and asked for a urine sample. That was basically it.

Whoever did the research on TMAU seemed to have got the current facts slightly mixed up. They were confusing trimethylamine with tyramine. At one point the Dr said it was tyramine that caused the smell. He asked the patient if cheese made his pulse race, cheese often being high in tyramine. Ironically tyramine is associated with the FMO3 enzyme, likely being a pathway to partly detoxify tyramine. High tyramine levels have been associated with migraines, though this does not seem to be consensually agreed. It can also be found in foods such as cheese and chocolate. Dr Eileen Treacy did some research a number of years ago to see if people with FMO3 deficiency tended to have high blood pressure, the theory being high levels of circulating catecholamine releasing agents (such as tyramine) can raise blood pressure, but it was found not to be so. Nevertheless, in theory it may be suspected that people with FMO3 deficiency may be sensitive to catecholamines (if they use the FMO3 enzyme for detoxification) until consensus shows this is not so.

So even though the researcher for the show got their facts confused, perhaps they are right about tyramine and raised pulses with FMO3 deficiency afterall !

Eileen Treacy 2005 Hypertension study in Ireland

2000 paper on FMO3 and tyramine by Cashman, Treacy et al

Consistent with the fact that human drug-metabolizing enzymes have endogenous substrates and are prevalent not as neutral balanced polymorphisms but for their selective advantages, we have previously shown that human FMO3 metabolizes biogenic amines such as tyramine and phenethylamine, resulting in formation of their oxime metabolites. Formation of oxime metabolites generally terminates the pharmacological activity of the parent amine (Lin and Cashman, 1997a,b). Herein, we show that the methionine variant at codon 257 of human FMO3 shows decreased N-oxygenation for the substrate tyramine. Tyramine is an indirectly acting sympathomimetic that exerts its pressor effect through amine uptake into the sympathetic nervous system with release of norepinephrine from synaptic vesicles. It is thus possible that human FMO3 polymorphisms affecting tyramine or other biogenic amine metabolism may predispose humans to variable tolerance to tyramine or other biogenic amine-containing foods and the associated symptoms (Reddy and Hayes, 1989; Stratton et al., 1991).

Quote from Nigel Manning TMAU PDF for Sheffield Children's Hospital

TMAU1 patients may suffer from adverse drug reactions (eg with codeine;
tamoxifen; ketoconazole; nicotine; cimetidine; ranitidine; phenothiazine).
Hypertension may result from ingestion of red wine and cheese (and
chocolate), which produce the neurotransmitter tyramine, another FMO3
dependent compound. Many people suffer from migraines associated with
tyramine containing foods and perhaps FMO3 deficiency may explain some of
these cases, but overall this demonstrates the adverse medical
consequences as well as the odour related psychosocial aspects.

wikipedia : tyramine

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