Synthetic and biosynthetic studies of porphyrins

The effects in vivo of mutationally modified uroporphyrinogen decarboxylase in different hem12 mutants of baker's yeast (Saccharomyces cerevisiae)

“…Uroporphyrinogen decarboxylase (uroporphyrinogen carboxylyase, EC 4.1.1.37) is the fifth enzyme of the haem-biosynthetic pathway and catalyses sequential decarboxylation of four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III, with formation of intermediates: hepta-, hexa-and pentacarboxyporphyrinogens [1][2][3]. Jackson et al [1] proposed that the stepwise decarboxylation of uroporphyrinogen III to coproporphyrinogen III proceeds in a clockwise fashion, starting with the acetic acid group in the D-ring of uroporphyrinogen III.…”

“…The enzyme has been purified from various sources [6][7][8][9], and its amino acid sequence was recently reported [10]. Despite many efforts to elucidate it, the mechanism of uroporphyrinogen decarboxylase action is still not clear [2,[4][5][6][7][8][9][11][12][13][14]; in particular, there is still controversy as to whether the sequential decarboxylations are catalysed by single active centre or separate active centres are involved.…”

Normal and abnormal heme biosynthesis. Part 7. Synthesis and metabolism of coproporphyrinogen-III analogues with acetate or butyrate side chains on rings C and D. Development of a modified model for the active site of coproporphyrinogen oxidase

“…Recrystallization from chloroform-methanol gave the dibutyrate (142 mg, 0.192 mmol, 68%) as a maroon solid, mp 140.5-141.5°C (lit. 10.84 (1H, s), 10.95 (1H, s); 13 Enzyme incubations and analyses of metabolic products were carried out as described elsewhere. For kinetic studies, the incubation products were isolated using a previously developed microassay technique 69 and analyzed by TLC and/or HPLC.…”

“…[5][6][7][8] Moreover, all 14 possible type III intermediates are metabolized by URO-D and the type I, type II and type IV isomers of uro'gen are also substrates for this enzyme. [9][10][11] However, the clockwise decarboxylation pathway does appear to be dominant at very low substrate concentrations. 5 Copro'gen-III is transferred into the mitochondria and undergoes two oxidative decarboxylations, promoted by coproporphyrinogen oxidase (CPO, EC 1.3.3.3) to produce proto'gen-IX (Scheme 1).…”

Biliverdin IX α, Intermediate and End Product of Tetrapyrolle Biosynthesis

“…[26,31]). Two molecules of ALA are condensed to porphobilinogen (PBG) [32] which in turn reacts to protoporphyrin IX via uroporphyrinogen [33,34], 7-,6-,5-carboxylic por phyrinogen, coproporphyrinogen (4-carboxylporphy- [35,36], 3-carboxylic porphyrinogen [37] ( Fig. 1) (also compare: [38]).…”