Monday, January 31, 2011

Cytochromes are us

Maya and Sunny
Cytochromes are complex heme based units responsible for carrying out some chemical reactions in the body. The liver has many of these systems used in part to detoxify certain substrates. These cytochromes metabolize many of the drugs we take.
Tamoxifen can reduce recurrences in estrogen positive breast cancer (arotamase inhibitors do a better job but have more painful side effects) by 30 %. However, Tamoxifen  is not the active drug. The cytochrome CYP2D6 in the liver converts it to active species. But there are some problems here. 7-10% of people have faulty CYP2D6 systems and you can't tell them by looking at them. Also some SSRIs (antidepressants) interfere with the metabolism too so the estrogen ends up not being blocked and is free to stimulate those rogue cancer cells.
Earlier studies have shown that the recurrence rates are higher with these cytochrome deficient people but a huge study just released at the San Antonio conference contradicts that. These people's overall survival seems identical. Doesn't make sense to me. Perhaps Tamoxifen itself has some activity..but the question I forget to ask the oncologist who presented this the other week is if suppressing estrogen is so important, then why don't they measure the levels to make sure this is happening? Yeah, the whole business doesn't affect me personally as my tumor was estrogen negative but it does affect the grand majority of cancer patients.
Other cytochromes are important too. About 10 years ago, grapefruit was found to interfere with the cytochrome P450. Certain drugs did not get metabolized as expected leading to much higher blood levels of these drugs. It is important that statins get metabolized in the liver by this enzyme system. If metabolism occurs in the muscle instead, bad things happen.

The local news keeps flashing warnings of some huge snowstorm tomorrow. It was clear and sunny today but so, so cold. I wimped out and ran inside.

Last night we had a family dinner at Josh and Julia's house. Baby Maya was her most charming. It was a pleasant evening.

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