Precursors porphyrin

Porphyrin dimers were also considered as photosensitisers and evaluated for PDT cancer treatment.53,54 The corresponding preparation involves porphyrinic precursors which can be prepared by following the Lindsey methodology.27,28 Thus, once those precursors have been prepared, several O-glycosylporphyrin dimers were synthesised.55 58... 

Derivative 10(p) was evaluated against HSV-1 and HSV-2. The results obtained have shown that the presence of a sugar moiety confers higher activity when compared with the porphyrinic precursor 9(p).13... 

The quantitative assay for PBG and ALA (Bio Rad, Hercules, CA, USA) that is based on the classical method by Mauzerall and Granick may be used for determination of the porphyrin precursors. PBG is absorbed by the anion-exchange column and ALA by the cation-exchange column interferences are washed out. After elution from the column, ALA is derivatized by acetyl acetone to form a pyrrole. Both ALA and PBG are determined colorimetrically with the modified Ehrlichs reagent. Instead of this broadly used standard method ALA, but not PBG may be detected and quantified using amino acid chromatography. However, our experience has shown that this method is only valid for detecting massively increased concentrations of ALA. 

Porphyrins and porphyrin precursors are assayed most often in a 24-h urine collected without additive. Alternatively, untimed urine samples may be used and excretion standardized to creatinine. The latter is especially recommended for children and in emergency situations. Alternative specimens for porphyrins are plasma, erythrocytes, and feces, depending on the medical indication. During collection and until arrival at the laboratory, specimens should be kept cold, preferably at about 4°C, and protected from light. Specimens in the laboratory are best kept frozen, as the metabolites in body fluids are stable at -20°C for at least 3 months. Some exceptions have been noted below. 

Porphyrinogens Porphyrin precursors exist in the chemically reduced form called porphyrinogens. In contrast to the porphyrins, which are colored, the porphyrinogens, such as uroporphyrinogen, are colorless. As described in the next section, porphyrinogens serve as intermediates between porphobilinogen and protoporphyrin in the biosynthesis of heme. 

Porphyrias are caused by inherited (or occasionally acquired) defects in heme synthesis, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors (see Summary Figure 21.7). With the exception of congenital erythropoietic porphyria, which is a genetically recessive disease, all porphyrias are inherited as autosomal dominant disorders. The mutations that cause the porphyrias are heterogenous (not all are at the same DNA locus), and nearly every affected family has its own mutation. Each porphyria results in the accumulation of a unique pattern of intermediates caused by the deficiency of an enzyme in the heme synthetic pathway. 

By comparing these results to those obtained using the vanadium porphyrin precursor, it can be concluded that vanadium from the porphyrin tends to stay on the matrix after thermal pretreatments (see Fig. 4), whereas vanadium from the naphthenate is preferentially associated with the zeolite after steaming, Fig. 9. These observations are in agreement with the report (1) that vanadium impregnated from vanadyl naphthenate migrated to the zeolite from the matrix surface during steam treatment. This different behavior of the two precursors... 

Intermediates may be different for the two vanadium precursors. For the porphyrin, calcination intermediates are found to be associated with aluminum in the matrix. No such relation has been found for the naphthenate. Pretreatment products are also different for the two precursors. Some amounts of EUVO4 are formed in the zeolite and no V2O5 is present in the matrix (at the V-loaded area) after calcination of the porphyrin-doped sample. The naphthenate-doped samples after calcination contain V02+ in the zeolite and V2O5 in the matrix (12). Steaming induces the formation of EUVO4 in the zeolite for samples prepared from either precursor. V2O5 is the main surface species generated by naphthenates (12), but it is not observed on samples loaded with V-porphyrin precursor. 

The transformation of porphyrin precursors to porphyrins, as well as the occurrence of these compounds in possible petroleum source materials and In petroleum, have considerable geochemical significance In the history of the origin and accumulation of petroleum. 

In healthy people, forming haemoglobin for their erythrocytes and haem-dependent enzymes, the rate of haem synthesis is controlled by negative feedback according to the amount of haem present. When more haem is needed there is increased production of the rate-controlling enzyme delta-aminolaevulinic acid (ALA) synthase which provides the basis of the formation of porphyrin precursors of haem. But in people with porphyria one or other of the enzymes that convert the various porphyrins to haem is deficient and so porphyrins accumulate. A vicious cycle occurs less haem —> more ALA synthase —> more porphyrin precursors, the metabolism of which is blocked, and a clinical attack occurs. 

Tab. 31.14 Porphyrin and porphyrin precursor content in urine and faeces for the differentiation of hepatic porphyrias (v = variable, N = normal) (s. tab. 31.10)...

The porphyrias are a heterogeneous group of diseases, all of which involve disorders of heme biosynthesis, which result in accumulation and increased excretion of porphyrins or porphyrin precursors. The porphyrias can be divided into two kinds the hereditary porphyrias, some of which can be exacerbated by exposure to certain chemicals, and the toxic porphyrias, which can be produced by exposure to certain chemicals alone. The pattern of excretion of porphyrins and porphyrin precursors is characteristic for each type. Clinical symptoms consist mainly of cutaneous photosensitivity and/or neurological disturbances. Hexachlorobenzene is a chemical inducer of porphyria. 

It was mentioned earlier that the acid-catalyzed cyclotetramerization of pyrrole (3) results in formation of a mixture of the four etioporphyrin type isomers ((4)-(7)). This involves a redistribution of the pyrrole subunits in intermediate pyrrole oligomers initiated by protonation of these electron-rich porphyrin precursors. Through a series of equilibria, the reaction produces... 

The porphyrin precursor octaethylporphrinogen (oepg) (10) has been used to form a yttrium complex [Li(thf)2][(oepg)Y(OEt)Li(thf)]. The ethoxide group, which is believed to arise from cleavage of thf, acts as a bridge between the yttrium and one lithium cation.146... 

Acute intermittent porphyria is associated with excessive urinary excretion of ALA and porphobilinogen. The lack of polymerization of porphobilinogen is due to deficiency of porphobilinogen deaminase in several cell types (e.g., hepatocytes, erythrocytes, fibroblasts, lymphocytes). Acute clinical manifestations include neuropsychiatric disorders and abdominal pain. The cause of these manifestations is not clear, but accumulation of porphyrin precursors (ALA and porphobilinogen) in pharmacological amounts has been implicated. Since afflicted subjects cannot make porphyrins to any great extent, they are not photosensitive. This disorder is inherited as an autosomal dominant trait. 

Porphyrias are diagnosed after demonstration and biochemical identification of the increased porphyrin precursor(s). Acute porphyrias are often misdiagnosed, and attacks can be fatal. The intravenous administration of heme or... 

The corrin macrocycle is derived biochemically from the porphyrin precursor uroporphyrinogen III [9]. However, it differs in several important respects from the porphyrin macrocycle. Perhaps the most important difference is the lack of the methene bridge between the A and D rings (carbon 20 in the porphyrin numbering system) which leads to a break in the conjugation, a loss of aromaticity, and a consequent buckling or non-planarity of the corrin macrocycle. Such buckling is readily apparent in the X-ray structure of 5 -deoxyadenosylcobalamin [10]. 

Early studies with PDT employed complex mixtures of poorly defined porphyrins known as hemato-porphyrin derivative (photofrin I) or a partially purified mixture known as porfimer sodium (PHOTOFRIN II) that was administered parenterally with subsequent irradiation using polychromatic light sources. The major problem with this approach was the prolonged period (4-6 weeks) of photosensitivity caused by skin retention of the porphyrin formulations. This led to a search for compounds that could be administered topically and that were eliminated more readily from the skin. The porphyrin precursor S-aminolevulinic acid (ALA) is converted to various porphyrins, particularly protoporphyrin (proto), in tissues including the skin (see below). Protoporphyrin subsequently is eliminated rapidly from the body, thereby minimizing the period of skin photosensitivity to a few hours. Topically applied ALA HCl (20% wA>) and, more recently, the methyl ester of ALA have been used successfully for the PDT of various types of nonmelanoma skin cancers and premalignant lesions. 

H.L. Bonokwosky, D.P. Tschudy, J. Collins, I. Doherty, R. Bossenmaier, A. Cardina, C.J. Watson (1971). Repression of the overproduction of porphyrin precursors in acute intermittent porphyria by intravenous infusions of hematin. Proc. Acad. Sci., 68, 2725-2729. 

To perform photodynamic therapy (PDT) in skin tumors, the most often used substance is ALA. The porphyrin precursor is topically applied under occlusive foil as described above. Irradiation should be performed when the optimal ratio of photosensitizer levels between tumor and normal tissue is reached (in the case of ALA 2-6 h after application Figures 2, 5, 7) [16]. The type of light source (laser or incoherent light) and the required fluence depend on the photosensitizer used as well as on the type and localization of the lesion. 

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