Cytochrome P 450 (CYP 450)

Its important to clarify the role of Cytochrome P450 and the role this enzyme plays in Porphyria.

To produce heme, your body needs to convert two simple substances, aminolaevulinate acid (ALA) and porphobilinogen (PBG), known as porphyrin precursors, into more complicated substances called porphyrins. These are then converted from one type of porphyrin into another to form, heme.

We have already discussed the importance of heme in the section "What is Porphyria",  and that it is required for many bodily functions. It is a component of haemoglobin, a vital protein which helps transport oxygen around your body and the pigment that gives red blood cells their colour.

Heme also helps to form many other important proteins and is found in all body tissues, but mostly in red blood cells, bone marrow and the liver and is required for the synthesis for several proteins in particular the cytochrome P450 system. Acute porphyria attacks are associated with increased production of heme products.

Upon activation of the P450 system, for example by P450-inducing drugs or hormones, heme is incorporated into the hepatic cytochromes, depleting its reservoir and increasing ALA synthetase activity with the excretion of porphyrins and attacks. The also occur with ingestion of hexachlorobenzene and with lead intoxication causing neurologic manifestations. The pathway is activated during increased heme synthesis. Patients with porphyris thus overproduce the precursors which are neurotoxic and excreted in urine and feces. Oxidation of these products gives the urine a port wine colour.

 

So, to  summarize, acute attacks are triggered when the levels of porphyrins in the body become highly elevated, whether this is due to a single trigger or a build up of chemical substances, medication, environmental factors, Infections, stress or often the exact cause/s cannot be identified.

Whatever the case may be if you have an acute and it is not managed correctly or un-diagnosed this can be potentially life threatening, damage can be caused to the liver, kidneys and other organs of the body. 

Read the article on Science Direct titled "Hepatic Porphria"