Macrocyclic intermediates in the biosynthesis of porphyrins

Abstract

The hepta-, hexa- and penta-carboxylic porphyrins found in the faeces of rats poisoned with hexachlorobenzene have been separated by high-pressure liquid chromatography and characterized largely by spectroscopie methods. Their structures were confirmed by total synthesis, as part of a programme in which eleven of the fourteen hepta-, hexa- and penta-carboxylic porphyrins derived from uroporphyrin III have now been synthesized as their methyl esters. The four isomeric heptacarboxylic and three of the pentacarboxylic porphyrinogens have been incubated with haemolysates of chicken erythrocytes, and they are all converted into protoporphyrin IX but at different rates. On the basis of this and other evidence we conclude that the decarboxylation of uroporphyrinogen III to coproporphyrinogen III is a stepwise process taking place by a preferred pathway (both in normal and abnormal metabolism); the acetic acid groups are decarboxylated in a sequential clockwise fashion starting with that on the D ring and followed by those on the A, B and C rings. In the poisoned rats the uroporphyrinogen decarboxylase enzyme (or group of enzymes) is probably partially inhibited and the pentacarboxylic porphyrinogen with an acetic acid group on ring C accumulates. The latter is then transformed by a side pathway into dehydroisocoproporphyrinogen and thence into dehydroisocoproporphyrin and its congeners.

High-Level Production of Porphyrins in Metabolically Engineered Escherichia coli : Systematic Extension of a Pathway Assembled from Overexpressed Genes Involved in Heme Biosynthesis

“…This enzyme accepts both urogen I and urogen III as substrates (19,32) and converts them to the corresponding coprogens. A significant amount of an intermediate with five carboxyl groups accumulated as a result of incomplete urogen I decarboxylation (Table 2).…”

Tetrapyrrole Metabolism inArabidopsis thaliana

“…The decarboxylations occur in an ordered fashion, beginning with the residue on ring D and proceed around the molecule in a clockwise direction (Jackson et al 1976). A plant UROD enzyme was first isolated from tobacco (Mock et al 1995) and two loci UROD1 (At2g40490) and UROD2 (At3g14930) encoding two UROD isoforms were identified in the Arabidopsis genome.…”

Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda.

“…The carboxyl groups are removed in a stepwise fashion from the acetate moiety of each of the pyrrole rings that make up the porphyrin macrocycle (1). The mechanism and number of catalytic sites are unknown, but models have been proposed with from one to four active sites (2)(3)(4).…”

“…The mechanism and number of catalytic sites are unknown, but models have been proposed with from one to four active sites (2)(3)(4). Unlike other decarboxylases, no cofactors are involved in catalysis (1). The cDNA and gene for human URO-D have been isolated and sequenced (5,6).…”