Biosynthesis of uroporphyrinogens. Interaction among 2-aminomethyldipyrrylmethanes and the enzymic system

Frydman, Rosalía B.; Levy, Esther; Valasinas, Aldonia; Frydman, Benjamiǹ

doi:10.1021/bi00594a015

Cited by 12 publications

(15 citation statements)

References 19 publications

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“…polymerization of 8. The decrease in the specific activity of isomer III was larger than the effect obtained with tripyrrane 7, and strongly resembled the results obtained with dipyrrylmethane 6 (see Frydman et al, 1978).…”

Section: Resultssupporting

confidence: 87%

“…These results agree with the results obtained when the 2aminomethyldipyrrylmethanes 6 and 9 were incubated with the enzymatic system. The former was incorporated only into isomer III (Frydman et al, 1978), while the latter was incorporated only into isomer I (Frydman et al, 1973).…”

Section: Discussionmentioning

confidence: 99%

“…The porphyrin concentration in the eluates was determined by a spectrophotometric method; the eluates were then plated on planchéis, and counted in a gas-flow counter. The control runs for the incorporation experiments described in Tables III and V were done by preparing two separate incubation mixtures (for a discussion of this method see Frydman et al, 1978). One contained (in a final volume of 100 µ ), 10 µ of phosphate buffer (pH 7.4), 8 nmol of porphobilinogen-14C, 25 µ of porphobilinogen deaminase, and 50 µ of uroporphyrinogen III co-synthase.…”

Section: Methodsmentioning

confidence: 99%

“…Since we found that dipyrrylmethane 6 was incorporated into 2 and not into 3 (Frydman et al, 1972(Frydman et al, , 1978, it follows that chain building to form uroporphyrinogen III (2) must start with dipyrrylmethane 6 (or its enzyme-bound equivalent), and grow through tripyrrane intermediates to form 2. Since it is the first intermediate of the process, the two further porphobilinogen units can became attached to it in only two possible ways.…”

mentioning

confidence: 98%

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Biosynthesis of uroporphyrinogens. Interaction among 2-aminomethyltripyrranes and the enzymic system

Frydman¹,

Levy²,

Valasinas³

et al. 1978

Biochemistry

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Many hypotheses on uroporphyrinogen biosynthesis advanced the possibility that 2-aminomethyltripyrranes formed by porphobilinogen deaminase are further substrates or uroporphyrinogen III co-synthase in the presence of porphobilinogen. These proposals were put to test by employing synthetic 2-aminomethyltripyrranes formally derived from porphobilinogen. None of them was found to be by itself a substrate of deaminase or of co-synthase in the presence of porphobilinogen. The tripyrranes chemically formed uroporphyrinogens by dimerization reactions, and the latter had to be deducted in control runs during the enzymatic studies. Two of the tripyrranes examined, the 2-aminomethyltripyrrane 7 and the 2-aminomethyltripyrrane 8, were found to be incorporated into enzymatically formed uroporphyrinogen III in the presence of porphobilinogen and of the deaminase-co-synthase system. While the former gave only a slight incorporation, the latter was incorporated in about 16%. No incorporation of 8 into uroporphyrinogen I was detected. On the basis of these results, and of the previous results obtained with 2-aminomethyldipyrrylmethanes, an outline of the most likely pathway of uroporphyrinogen III biosynthesis from porphobilinogen is given.

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Section: Resultssupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 98%

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Biosynthesis of uroporphyrinogens. Interaction among 2-aminomethyltripyrranes and the enzymic system

Frydman¹,

Levy²,

Valasinas³

et al. 1978

Biochemistry

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“…Uroporphyrinogen III cosynthetase (Uro-S, cyclizing enzyme, EC 4.2.1.75) is found in the cytosol. Without this enzyme, HMB forms Urogen I, a non-physiological isomer of Urogen III, non-enzymatically (14). Tsai et al, (15) cloned the human Uro-S gene.…”

Section: Protogen Oxidase (Mitochondria)mentioning

confidence: 99%

Porphyrins as Chemotherapeutic Agents

Rebeiz

Kelley

Rebeiz

1994

Porphyric Pesticides

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Porphobilinogen deaminase and uroporphyrinogen III synthase: Structure, molecular biology, and mechanism

Shoolingin‐Jordan

1995

J Bioenerg Biomembr

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Porphobilinogen deaminase (hydroxymethylbilane synthase) and uroporphyrinogen III synthase (uroporphyrinogen III cosynthase) catalyze the transformation of four molecules of porphobilinogen, via the 1-hydroxymethylbilane, preuroporphyrinogen, into uroporphyrinogen III. A combination of studies involving protein chemistry, molecular biology, site-directed mutagenesis, and the use of chemically synthesized substrate analogs and inhibitors is helping to unravel the complex mechanisms by which the two enzymes function. The determination of the X-ray structure of E. coli porphobilinogen deaminase at 1.76 A resolution has provided the springboard for the design of further experiments to elucidate the precise mechanism for the assembly of both the dipyrromethane cofactor and the tetrapyrrole chain. The human deaminase structure has been modeled from the E. coli structure and has led to a molecular explanation for the disease acute intermittent porphyria. Molecular modeling has also been employed to stimulate the spiro-mechanism of uroporphyrinogen III synthase.

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Biosynthesis of uroporphyrinogens. Interaction among 2-aminomethyldipyrrylmethanes and the enzymic system

Cited by 12 publications

References 19 publications

Biosynthesis of uroporphyrinogens. Interaction among 2-aminomethyltripyrranes and the enzymic system

Biosynthesis of uroporphyrinogens. Interaction among 2-aminomethyltripyrranes and the enzymic system

Porphyrins as Chemotherapeutic Agents

Porphobilinogen deaminase and uroporphyrinogen III synthase: Structure, molecular biology, and mechanism

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