Transformation of porphobilinogen into porphyrins by preparations from human erythrocytes

Cornford, Pamela

doi:10.1042/bj0910064

Cited by 58 publications

(23 citation statements)

References 21 publications

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“…Hemolysates from the patients with PCT demonstrated decreased URODECARB activity with either substrate and, as with the controls, there was no difference in the activity of the erythrocyte enzyme in decarboxylating uroporphyrinogen I or III.-The equivalent decarboxylation of either substrate is in agreement with the findings of Romeo and Levin for mouse spleen URODECARB (36) and our own finding for porcine hepatic URODECARB (25). Although older data suggest that the rate of decarboxylation is higher with the type III isomer (37)(38)(39), Inherited Enzymatic Defect in Porphyria Cutanea Tarda 1095 the current studies support the validity of assaying human hepatic URODECARB with uroporphyrinogen I as the substrate. If URODECARB deficiency is the underlying defect in heme biosynthesis in PCT, then the question arises as to why no heme deficiency is observed.…”

Section: Introductionsupporting

confidence: 82%

An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity.

Kushner¹,

Barbuto²,

Lee³

1976

J. Clin. Invest.

269

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A B S T R A C T Uroporphyrinogen decarboxylaseWith the erythrocyte assay, multiple examples of decreased uroporphyrinogen decarboxylase activity were detected in members of three families of patients with porphyria cutanea tarda. In two of these families subclinical porphyria was also recognized. The inheritance pattern was consistant with an autosomal dominant trait.The difference in erythrocyte enzymatic activity between men and women was not explained but could have been due to estrogens. This possibility was supported by the observation that men under therapy with estrogens for carcinoma of the prostate had values in the normal female range.

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Section: Introductionsupporting

confidence: 82%

An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity.

Kushner¹,

Barbuto²,

Lee³

1976

J. Clin. Invest.

269

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“…URODECARB has been reported to catalyze the decarboxylation of UROGEN III at a faster rate than UROGEN I (12,23). However, Romeo and Levin found that URODECARB extracted from mouse spleen decarboxylates both isomers at the same rate (11).…”

Section: Discussionmentioning

confidence: 99%

The role of iron in the pathogenesis of porphyria cutanea tarda. II. Inhibition of uroporphyrinogen decarboxylase.

Kushner¹,

Steinmüller²,

Lee³

1975

J. Clin. Invest.

127

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A B S T R A C T Porphyria cutanea tarda is characterized biochemically by excessive hepatic synthesis and urinary excretion of uroporphyrin I and 7-carboxyl porphyrins. This pattern of excretion suggests an impaired ability to decarboxylate uroporphyrinogen to the 4-carboxyl porphyrinogen, coproporphyrinogen, a reaction catalyzed by the enzyme uroporphyrinogen de-carboxylase.Because clinical evidence has implicated iron in the pathogenesis of porphyria cutanea tarda, these experiments were designed to study the effect of iron on uroporphyrinogen decarboxylase in porcine crude liver extracts.Mitochondria-free crude liver extracts were preincubated with ferrous ion and aliquots were assayed for uroporphyrinogen decarboxylase activity. Uroporphyrinogens I and III, the substrates for the decarboxylase assay, were prepared enzymatically from [3H]porphobilinogen. The products of the decarboxylase reaction were identified and quantitated by three methods: (a) extraction into ethyl acetate at pH 4.0, back extraction into 1.5 N HCO and spectrophotometric quantitation; (b) adsorption onto talc, esterification, paper chromatographic identification, and quantitation by liquid scintillation counting; and (c) adsorption onto talc, esterification, thin-layer chromatographic identification on silica gel, and quantitation by liquid scintillation counting. The thin-layer scintillation method proved most sensitive as it was the only method which accurately identified and quantitated the 7-carboxyl porphyrin reaction product. Uroporphyrinogens I and III were decarboxylated at the same rate by porcine hepatic uroporphyrinogen decarboxylase, and the addition of iron induced marked inhibition of the decarboxylase activity. Orthophenanthroline blocked the inhibitory effect of iron.The inhibition of uroporphyrinogen decarboxylase by ferrous ion, coupled with its previously reported inhibitory effect on uroporphyrinogen III cosynthetase, provides a possible biochemical explanation for the pattern of urinary porphyrin excretion observed in patients with porphyria cutanea tarda and the clinical association with disordered iron metabolism.

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“…Reports about heat stability and effect of different sodium salt concentrations on the stepwise decarboxylation [l, 4,8,9,22] and the rates of decarboxylation towards different substrates [4, 9, 20, 21, 231 suggest the presence of more than one active centre. Evidence from studies of partially purified enzyme [8, 21, 241 and of uroporphyrinogen decarboxylase purified to homogeneity [l, 4, 51 indicated that the decarboxylation of uroporphyrinogen to coproporphyrinogen is catalyzed by a single protein.…”

Section: Discussionmentioning

confidence: 99%

Studies on uroporphyrinogen decarboxylase of etiolated Euglena gracilis Z

Juknat

Seubert

et al. 1989

European Journal of Biochemistry

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A 423‐fold purified fraction of uroporphyrinogen decarboxylase (EC 4.1.1.37) showing a specific activity of 770 units/mg protein has been employed in order to study some properties in etiolated Euglena gracilis Z. Uroporphyrinogen decarboxylase has a relative molecular mass of 54000, an optimum pH of 7.2 and exhibits Michaelis‐Menten kinetics, employing both uroporphyrinogen I and uroporphyrinogen III as substrates. Anaerobic conditions seem not to be necessary for uroporphyrinogen decarboxylase activity. Neither EDTA nor cysteine affected enzyme activity, whereas dithiothreitol produced a remarkable activation of coproporphyrinogen formation. Kinetic data employing both substrates showed an accumulation of porphyrinogen (i.e. hexa‐ and heptaporphyrin) containing six or seven COOH groups, depending on the uroporphyrinogen concentration used. An unusual elution profile of the intermediates on Sephacryl S‐200 was found.

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Transformation of porphobilinogen into porphyrins by preparations from human erythrocytes

Cited by 58 publications

References 21 publications

An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity.

An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity.

The role of iron in the pathogenesis of porphyria cutanea tarda. II. Inhibition of uroporphyrinogen decarboxylase.

Studies on uroporphyrinogen decarboxylase of etiolated Euglena gracilis Z

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