Liver - Cytochrome P-450

Cytochrome P450

Cytochrome P450 is a family of the body's more powerful detox enzymes. Over 60 key forms are known, with hundreds of genetic variations possible, producing a wide variety of susceptibility to specific toxins. As the saying goes, "One man's meat is another man's poison".

Problems with P450 are often involved in porphyria type disorders. P450 production may be inhibited or substantially used up by H2 blockers, some antacids, SSRI's (Prozac, Paxil, Zoloft, etc.,) and perhaps one fifth of all medications. In this manner, these drugs have the potential to worsen, or even create, a susceptibility to many common chemicals, and thus may trigger Multiple Chemical Sensitivities / Environmental Illness and related syndromes. The oddness of some of these symptoms may prompt some doctors to prescribe SSRI's, thus making the situation worse.

Long term inhibition of heme synthesis due to P450 insufficiency may cause anemia. This, and the resulting metabolic reductions, may cause reductions in the body's ability to maintain itself, showing up as a wide variety of health problems similar to those of Wilson's Syndrome, as well as behavioral and cognitive problems similar to those described in The Cold Body Page. A related detoxification pathway involves Paraoxonase and related oxonases.

Porphyria

Diseases characterized by problems in the heme synthesis biochemical pathways. (See chart below.) This is often the base cause of Multiple Chemical Sensitivities (MCS), light sensitivity, some forms of skin problems, and wine colored or purple urine; but is not the only condition that can cause these problems.

Often, problems in the Cytochrome P-450 heme synthesis and detoxification pathways show up as porphyria type problems.

It has been reported that many persons with Multiple Chemical Sensitivity have heme related problems. Some forms are hereditary, yet a growing number of cases are being reported involving chemical exposures and drug interactions (e.g. Prozac, Zoloft, antacid medications and others.) The P450 system will break these drugs down, using up the P450 feedstocks which would otherwise be used to produce red blood. It is said that about one fifth of our pharmaceuticals affect the P450 pathways.

As P450 feedstocks are diverted from heme synthesis to deal with these drugs and other environmental toxins, other materials (called porphyrinogens,) in the heme synthesis pathways build up and become oxidized in the blood stream to form porphyrins, which absorb light more strongly, even through the skin, and can cause porphyria type symptoms. If the problem is related to short term chemical exposures, the porphyria may be intermittent, making it harder to get a clear diagnosis. (Most hospital urine tests only test for the rarer forms.) It is one of the complaints of many Gulf War Veterans.

Diagnosis can be difficult. This is particularly true when the patient has not been recently exposed, and may no longer be exhibiting strong symptoms or biochemical abnormalities; yet P450 levels may remain low enough to allow transient porphyrias on exposure to common chemicals.

In addition to chemical exposure, exposure to ultraviolet and sometimes even blue light can affect many forms of porphyria. Urine is sometimes discolored during or before an attack: red, orange, purple, even green have been seen at times. But sometimes the porphyrins are excreted via the gall bladder, and never show in the urine.

(One simple test for porphyria is to expose a cup of urine to sunlight for the better part of a day. If the urine becomes wine colored or purple, porphyria is probable. However, lack of color changes will NOT indicate that prophyria is unlikely.)

Some of the more severe symptoms may include skin lesions, mental instability, and neuropathy. Dextrose 10% IV may help in a crisis, as may IV Heme if the dextrose is not enough.

Another problem may involve Subclinical Hypothermia , or Wilson's Syndrome. This is sometimes mistreated as "Thyroid Problems", using Synthroid, when a more balanced T3/T4 treatment may be more beneficial. (However, before considering glandular based therapies, read Mad Cow.) Every degree F below normal can reduce the efficiency of some enzymes by up to 20%. As enzymatic efficiency falls with temperature, symptoms mimicking those of genetic enzyme deficiencies (e.g. porphyria,) may manifest themselves and result in diagnostic inaccuracies. With reduced heme production, reduced oxygen transport may reduce metabolism, thus reducing body temperature, further interfering with P450 and other enzymatic systems. Low body temperature can have behavioral effects as well as interfering with a wide array of repair mechanisms, thus producing many seemingly unrelated symptoms in the same patient.