Uroporphyrin

A mild procedure which does not involve strong adds, has to be used in the synthesis of pure isomers of unsymmetrically substituted porphyrins from dipyrromethanes. The best procedure having been applied, e.g. in unequivocal syntheses of uroporphyrins II, III, and IV (see p. 251f.), is the condensation of 5,5 -diformyldipyrromethanes with 5,5 -unsubstituted dipyrromethanes in a very dilute solution of hydriodic add in acetic acid (A.H. Jackson, 1973). The electron-withdrawing formyl groups disfavor protonation of the pyrrole and therefore isomerization. The porphodimethene that is formed during short reaction times isomerizes only very slowly, since the pyrrole units are part of a dipyrromethene chromophore (see below). Furthermore, it can be oxidized immediately after its synthesis to give stable porphyrins. 

P-2 mesoporphyrin, P-4 coproporphyrin, P-5 pentaporphyrin, P-6 hexaporphyrin, P-7 heptaporphyrin, P-8 uroporphyrin. 

In connection with this development it is worth mentioning that uroporphyrinogen III (8), the reduced form of uroporphyrin III (9), is the key building block of all naturally occurring porphinoid structures known at present. 

Bachowski GJ, Girotti AW (1988) Light-stimulated formation of hydrogen peroxide and hydroxyl radical in the presence of uroporphyrin and ascorbate. Free Radic Biol Med 5 3-6... 

Uronic acids 154,199, 322,426 Uroporphyrin 102 Ursolic acid 59, 71 UV lamps 13,14,16,137 with camera holder 13,17,136 UV absorber in plastics 281... 

The arrangement of the acetate (A) and propionate (P) substituents in the uroporphyrin shown in Figure 32-2 is asymmetric (in ring IV, the expected order of the A and P substituents is reversed). A porphyrin with this type of asymmetric substitution is classified as a type III porphyrin. A porphyrin with a completely symmetric arrangement of the substituents is classified as a type I porphyrin. Only types I and III are found in nature, and the type III series is far more abundant (Figure 32-3)—and more important because it includes heme. 

Figure 32-2. Uroporphyrin III. A (acetate) = —CHjCOOH P (propionate) =—CHjCHjCOOH.

Uroporphyrins were first found in the urine, but they are not restricted to urine. 

Coproporphyrins and uroporphyrins are of chnical interest because they are excreted in increased amounts in... 

Urinary porphobilinogen positive, urinary uroporphyrin positive, fecal protoporphyrin positive... 

The above account of selectivity of inorganic plus organic chemistry in synthesis is given rather extensively to stress three points. All the four (Mg, Fe, Co and Ni) porphyrin products came from one source, the synthesis of uroporphyrin. The basis of selection is very different from that in primitive centres which use thermodynamic stability constant selectivity based on different donor atoms for different metal ions. Here, all ion complexes have the same donor atoms, nitrogen, the most constrained being the coordination of Mg2+ by five nitrogens exactly as is seen for Fe in haemoglobin. Hence, there also has to be a new control feedback to ensure that the appropriate quantities of each metal cofactor is produced in a balanced way, that is synthesis from uroporphyrin has to be divided based upon... 

An early account194 describes an attempt to use 64Cu complexes of haematoporphyrin, protoporphyrin, uroporphyrin, and coproporphyrin to detect tumors preferential localization in tumors was not observed. It needs to be recognized that metalation can change solution... 

All dead in 11 days thymic involution and edema gross accumulations of uroporphyrins in liver... 

Hb and Ni-reconstituted Hb were prepared according to reported methods (13). Mb was made by the method of Alston and Storm (14) Solutions of the proteins in 0.05 M phosphate buffer at pH 7.5 were used for obtaining spectra. The proteins are stable in air and do not photodecompose. Ni protoporphyrin IX (Ni(ProtoP)), Ni uroporphyrin I (Ni(UroP)), and Ni octaethylporphyrin (Ni(OEP)) were obtained from Porphyrin Products and used without further purification. All solvents were of highest purity obtainable from commercial sources. All materials showed the literature uv-visible absorption spectra. Absorption spectra were obtained on a Perkin-Elmer Model 330 spectrophotometer. 

These effects are due to deficiency of uroporphyrin decarboxylase, one of the enzymes of the heme synth e tic path way. 

Let me put it to Professor Lehn that biology can do better than he can with small molecules. From uroporphyrin biology makes (1) copper porphyrins (turacin feathers), (2) heme (iron) porphyrins, (3) magnesium chlorins, (4) cobalt corrins (B12). These compounds are formed with very little confusion between metals and partners. I cannot give selectivity factors, but they are very big. How is this managed Is it not better than man can do Maximum size selectivity for anions is not yet understood as few anion-binding sites in biology are known. 

HMBS hydroxymethylbilane-synthase, Intermediaries heptacarboxy-, hexacarboxy-and pentacarboxyporphyrins, MIM Nr Mendelian Inheritance in Man number, PCT porphyria cutanea tarda, Proto protoporphyrin IX, PV porphyria variegata, Uro uroporphyrin... 

The first porphyrin intermediate of the biosynthetic pathway is uroporphyrinogen, which is stepwise decarboxylated by uroporphyrinogen decarboxylase to heptacarboxy-, hexacarboxy-, pentacarboxy-, and coproporphyrinogen. This latter compound proceeds, as indicated in Fig. 7.3.1, to protoporphyrinogen and protoporphyrin. The oxidized uroporphyrin and its decarboxylation products up to coproporphyrin are assayed in urine. Coproporphyrin and the further downstream intermediaries can be recovered from feces as described below. 

Increased porphyrins in clear fluid such as urine may be detected directly by their pink fluorescence if exposed to long ultraviolet (Fig. 7.3.2). The specificity of this screening assay may be improved if porphyrins are extracted by talcum [8]. These isolated porphyrins may be quantified using a spectrofluorimeter. As different porphyrias show specific excretion patterns, separation of the main porphyrins is desirable. The formerly used fractionated extraction enabled to separate the uroporphyrin fraction from the coproporphyrin fraction. In addition to uroporphyrin, the first fraction includes heptacarboxy- and part of hexacarboxyporphyrins, and in addition to coproporphyrin, the second fraction includes part of hexacarboxy- and pentacar-boxyporphyrins. Later on, thin-layer chromatography of methylester derivatives is used. 

All acute porphyrias show similar urinary porphyrin patterns with predominant elevation of uroporphyrin and coproporphyrin III isomer in addition, hepta-, hexa-, and especially pentacarboxyporphyrins are increased (see Fig. 7.3.3). 

Table 7.3.3 Example mean reference values for uroporphyrin, coproporphyrin I, and coproporphyrin III (these can only be interpreted as a guidance) collected by means of high-performance liquid chromatography (HPLC). The intermediary porphyrins were below the detection limit...

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