The effects of cytochrom P450 synthesis on heme synthesis

[MudPhud20XX]

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Kaplan biochem says that barbiturates should not be given to patients with porphyrias since barbiturate induces cytochrome P450 synthesis which reduces heme level. As a result, enzymes in heme synthesis are turned on and increase the accumulation of porphyrin precursors exacerbating symptoms in porphyria such as in acute intermittent porphyria.

Can anyone explain the connection between cytochrome P450 and heme level? Is it the iron? Or is heme being consumed to make cytochrome P450?

Many thanks in advance.

 

[notbobtrustme]

my guess is that p450 speeds up the degradation of heme, but I have nothing to back that up.

 

[BurberryDoc]

Kaplan biochem says that barbiturates should not be given to patients with porphyrias since barbiturate induces cytochrome P450 synthesis which reduces heme level. As a result, enzymes in heme synthesis are turned on and increase the accumulation of porphyrin precursors exacerbating symptoms in porphyria such as in acute intermittent porphyria.

Can anyone explain the connection between cytochrome P450 and heme level? Is it the iron? Or is heme being consumed to make cytochrome P450?

Many thanks in advance.

Cytochrome P450 CONTAIN and REQUIRE heme as a cofactors for their function. Barbiturate dosage leads to increased use, turnover, and synthesis of P450 enzymes, and so this requires increased synthesis of heme, which is impaired in a porphyria patient, so this need for increased heme cannot be met efficiently, adequately, or at all. That is why porphyria patients should not receive barbiturates.

 

[notbobtrustme]

Cytochrome P450 CONTAIN and REQUIRE heme as a cofactors for their function. Barbiturate dosage leads to increased use, turnover, and synthesis of P450 enzymes, and so this requires increased synthesis of heme, which is impaired in a porphyria patient, so this need for increased heme cannot be met efficiently, adequately, or at all. That is why porphyria patients should not receive barbiturates.

perfect explanation, I remember this exactly from biochem now that I see it.

 

[BurberryDoc]

perfect explanation, I remember this exactly from biochem now that I see it.

I'm a graduate student but I will be beginning medical school next year. VERY nice to see this is the kind of stuff I can expect to see on step I 🙂

Glad I was able to help!

 

[AnalisCanalis]

Additionally, heme inhibits ALAS1(the first step in heme synthesis). A decreased level of heme will therefore further increase synthesis and accumulation of intermediates seen in porphyrias.

EDIT: oh, nvm