Accumulation, Highly carboxylated porphyrins leads to Uroporphyria

Accumulation of porphyrins causes both physical and chemical damage to tissues, resulting in what is generally termed porphyria. The ability of porphyrins to absorb light of 400–410 nm (the Soret band) is the key factor in producing the photocutaneous lesions observed on sun exposed areas in affected individuals. The porphyrins absorb this light and enter a high energy state, which is then transferred to molecular oxygen resulting in reactive oxygen species (ROS). These ROS cause phototoxic damage and further catalyze the oxidation of porphyrinogens to porphyrins. Some porphyrins, mainly uroporphyrin and heptacarboxyl porphyrin, form needle-shaped crystals resulting in hydrophilic cytoplasmic inclusions^[1]. Porphyrins demonstrate a range of water solubilities, and therefore show unique tissue and cellular distributions, resulting in different patterns of phototoxic damage histologically and cytologically^[2].

 

Violet light excites the delocalized electrons in porphyrins. If the energy is not given out as red fluorescent light, it is passed onto oxygen to form tissue damaging free radicals. (Source: Sarkany, R. P. (2008).Photodermatol. Photoimmunol. Photomed. 24(2), 102-108.)

Is it known how much change in the first event is needed to impact the second? Are there known modulators of the response-response relationships? Are there models or extrapolation approaches that help describe those relationships?

Humans

According to the U.S. National Library of Medicine^[5], red blood cell porphyrin levels in healthy individuals should lie within the following ranges:

• Total porphyrin levels: 16 to 60 mcg/dL
• Coproporphyrin level: < 2 mcg/dL
• Protoporphyrin level: 16 to 60 mcg/dL
• Uroporphyrin level: < 2 mcg/dL

The European Porphyria Network details the minimum laboratory requirements necessary for diagnosing each type of porphyria ^[6].

Rodents

Studies in mice show trace amount of hepatic and urinary porphyrins in normal individuals (total porphyrins <1 nmol/g liver and < 1 µM, respectively)^[7,8,9].  Healthy rats were shown to have total hepatic porphyrin levels ranging from 0.78-1.22 nmol/g liver^[10], and urinary excretion of uroporphyrin < 5 µg a day^[11].

Birds

Fox and colleagues (1988)^[12] screened for highly carboxylated porphyrins (HCPs) in 8 wild bird species in relatively uncontaminated areas, and found that healthy individuals should contain no more than 25 pmol HCPs/g liver.  The livers of puffins, chickens, quail, doves and finches and herring gulls contained 4 to 24 pmol HCPs/g and fulmars and murres  contained  a maximum of 12 pmol HPCs/g liver.

This relationship exists in birds^[3] and mammals, including humans^[4].