Protoporphyrin IX

About: Protoporphyrin IX is a research topic. Over the lifetime, 2250 publications have been published within this topic receiving 65544 citations. The topic is also known as: PpIX.

Equilibrium and kinetic studies of the aggregation of porphyrins in aqueous solution

Abstract: An investigation of the behavior of protoporphyrin IX, deuteroporphyrin IX, haematoporphyrin IX and coproporphyrin III in aqueous solution revealed extensive and complex aggregation processes Protoporphyrin appears to be highly aggregated under all conditions studied At concentrations below 4 muM, aggregation of deutero-, haemato- and coproporphyrin is probably restricted to dimerization At approx 4muM each of these three porphyrins exhibits sharp changes in spectra consistent with a "micellization" process to form large aggregates of unknown size This critical concentration increases with increasing temperature and pH, but is not very sensitive to variation in ionic strength Temperature-jump kinetic studies on deuteroporphyrin also imply an initial dimerization process, the rate constants for which are comparable with those for various synthetic porphyrins, followed by a further extensive aggragation The ability of a particular porphyrin to dimerize appears to parallel that of the corresponding iron(III) complexes (ferrihaems), although it is thought that ferrihaems do not exhibit further aggregation under these conditions

Activation of purified soluble guanylate cyclase by protoporphyrin IX

Abstract: Soluble guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] purified from bovine lung is markedly activated (30- to 40-fold) by protoporphyrin IX (Ka, 15-25 nM) and is inhibited by hematin (Ki, 3.7 microM) when MgGTP is used as substrate. Guanylate cyclase possesses specific activities (mumol of cGMP per min/mg of protein) of 0.1-0.2 (MgGTP) and 0.3-0.5 (MnGTP) and can attain values of 2-8 (MgGTP) or 1-1.4 (MnGTP) in the presence of protoporphyrin IX. Guanylate cyclase purified in this study contains heme and is activated by nitric oxide and nitrosyl-heme to the same magnitude as that by protoporphyrin IX. With the exception of hematoporphyrin IX, close structural analogs of protoporphyrin IX, including precursors and metabolites, do not activate guanylate cyclase. The insertion of iron into protoporphyrin IX to form heme or hematin renders the metalloporphyrin an inhibitor of unactivated or activated guanylate cyclase. The data suggest that protoporphyrin IX and heme could function to modulate guanylate cyclase activity.

Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer

Abstract: Aminolevulinic acid (ALA) is an endogenous metabolite normally formed in the mitochondria from succinyl-CoA and glycine. Conjugation of eight ALA molecules yields protoporphyrin IX (PpIX) and finally leads to formation of heme. Conversion of PpIX to its downstream substrates requires the activity of a rate-limiting enzyme ferrochelatase. When ALA is administered externally the abundantly produced PpIX cannot be quickly converted to its final product - heme by ferrochelatase and therefore accumulates within cells. Since PpIX is a potent photosensitizer this metabolic pathway can be exploited in photodynamic therapy (PDT). This is an already approved therapeutic strategy making ALA one of the most successful prodrugs used in cancer treatment.

Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging.

Abstract: Heme, a major functional form of iron in the cell, is synthesized in the mitochondria by ferrochelatase inserting ferrous iron into protoporphyrin IX. Heme deficiency was induced with N-methylprotoporphyrin IX, a selective inhibitor of ferrochelatase, in two human brain cell lines, SHSY5Y (neuroblastoma) and U373 (astrocytoma), as well as in rat primary hippocampal neurons. Heme deficiency in brain cells decreases mitochondrial complex IV, activates nitric oxide synthase, alters amyloid precursor protein, and corrupts iron and zinc homeostasis. The metabolic consequences resulting from heme deficiency seem similar to dysfunctional neurons in patients with Alzheimer's disease. Heme-deficient SHSY5Y or U373 cells die when induced to differentiate or to proliferate, respectively. The role of heme in these observations could result from its interaction with heme regulatory motifs in specific proteins or secondary to the compromised mitochondria. Common causes of heme deficiency include aging, deficiency of iron and vitamin B6, and exposure to toxic metals such as aluminum. Iron and B6 deficiencies are especially important because they are widespread, but they are also preventable with supplementation. Thus, heme deficiency or dysregulation may be an important and preventable component of the neurodegenerative process.