Two of the several types of porphyria will serve to illustrate some of the biochemical issues involved.
Acute intermittent porphyria is a defect of hepatic uroporphyrinogen I synthase activity.
porphobilinogen (the substrate) accumulates, and is excreted in the urine. Note: analysis of the urine for porphobilinogen is relatively simple.
Heme synthesis is reduced. As a result, there is no feedback inhibition of ALA synthase, nor is there repression of synthesis of the enzyme protein. ALA synthase activity therefore increases.
Insufficient 5-alpha steroid reductase activity shunts steroids into the 5-beta reductase pathway, whose products further stimulate ALA synthase.
There are neurological symptoms, including agitation, which cannot be explained. Administration of barbiturates to sedate an agitated patient would be counterproductive, as it would further activate ALA synthase, and result in more rapid clinical deterioration.
Hereditary coproporphyria (pronounce) is a defect of hepatic coproporphyrinogen oxidase.
Large amounts of coproporphyrin III are excreted in the feces.
Poorly understood neurological symptoms occur.
Skin lesions may occur.
Porphyrinogens are subject to light-catalyzed oxidation to their corresponding porphyrins.
Porphyrins absorb visible light strongly. Exposure to strong visible light (sunlight) may cause pruritis, edema and so forth. The most damaging wavelength is 405 nm, which is the peak of the absorption spectra of porphyrins. This wavelength is not blocked by window glass.
