Protoporphyrinogen oxidase

Protoporphyrinogen oxidase catalyzes the six-electron oxidation of protoporphyrinogen IX to protoporphyrin IX. Application of the assay to leukocytes provides a more convenient enzyme source than liver tissues in the diagnosis of porphyrias. 

The product, protoporphyrin IX, is separated from mesoporphyrin, the internal standard, on an ODS-Hypersil column (5 mm x 250 mm). The mobile phase was 88% (v/v) methanol in 1 M ammonium acetate, pH 5.16. Fluorescence detection was used with excitation at 400 nm and emission at 618 nm. 

Enzyme activity was measured in leukocytes isolated from heparinized blood. 

The p-nitrodiphenyl ethers (NDPEs) are a group of broad-spectrum herbicides, introduced in 1962, whose mechanism of action has been the 

Several modes of action have been proposed for some individual NDPEs—for example, inhibition of PSII (nitrofen) and inhibition of carotenogenesis (non-p-nitro DPEs). However, such effects cannot be attributed to all NDPEs. The question of a role for photosynthesis in NDPE action is controversial. Oxyfluorfen has been proposed to be activated by probable reduction by ferredoxin to a p-nitro derivative which is proposed to be capable to inducing lipid peroxidation. However, this mechanism cannot be applied to other NDPEs nor for acifluorfen methyl analogues where p-nitro is replaced by Cl or H. In addition, NDPEs are active in chlorophyll-free and photosynthetically incapable plant tissues.Direct irradiation of nitrofen and chlomethoxyfen in solution can lead to anionic radicals which may be capable of inducing lipid peroxidation. However, 

Carotenoids, or caroteno-proteins have been proposed as photoreceptors mediating NDPE phytotoxicityHowever, action spectra of aci-fluorfen methyl activity showed two peaks at 450 and 670 nm suggesting both carotenoid and chlorophyll involvement. A study with S-23142 showed major peaks at 550 and 650 nm with only a minor peak at 450 nm indicating chlorophyll or a similar component as the major photoreceptor.  

In treated cells, accumulated protoporphyrinogen IX is proposed to diffuse from its site of synthesis and is subjected to nonenzymatic oxidation to protoporphyrin IX. The abnormal cell location, beyond the reach of 

The mechanism of inhibition of protoporphyrinogen oxidase by NDPEs and related structures has yet to be elucidated. However, mammalian yeast and plant enzymes appear similarly sensitive, indicating cause for concern with respect to toxicological problems. 

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Protoporphyrinogen oxidase (protox), crop resistance to, 73 361-362 Prototype pilot plants, 79 459 Protoveratrine A, 2 105 Prourokinase, 5 175, 178... 

NADPH DEHYDROGENASE NITRATE REDUCTASE PROTOPORPHYRINOGEN OXIDASE SARCOSINE DEHYDROGENASE SULFITE REDUCTASE FoFi-ATPase (and RELATED PROTONTRANSPORTING ATPases)... 

PROTOPORPHYRINOGEN OXIDASE PUTRESCINE OXIDASE PYRUVATE OXIDASE QUERCETIN 2,3-DIOXYGENASE... 

PROTOPORPHYRINOGEN OXIDASE Pseudo-asymmetric carbon atom, STEREOCHEMICAL TERMINOLOGY, lUPAC RECOMMENDATIONS Pseudo-axial,... 

E Inhibition of protoporphyrinogen oxidase (PPO) Diphenyl ethers JV-Phenylphthalimides Thiadiazoles Oxadiazoles Triazolinones 14... 

Affected enzyme ALA-dehy- dratase Hydroxymethyl-bilane synthase Uroporphyrinogen III synthase Uroporphyrinogen decarboxylase Coproporphyrinogen oxidase Protoporphyrinogen oxidase Ferrochelatase... 

An acute disease caused by a deficiency in protoporphyrinogen oxidase. 

Diphenyl ether herbicides. The diphenyl ether class of herbicides belongs to a broader area of herbicides known as protoporphyrinogen oxidase (Protox) herbicides [20,21], Diphenyl ether herbicides were initially introduced over four decades ago in the 1960s with the discovery of nitrofen by Rohm and Haas (now Dow AgroSciences) [22] and bifenox by Mobil [23], These early diphenyl ether herbicides did not attain a significant role in the control of weeds in commercial crops until the 1970s, with the introduction of the trifluoromethyl compounds oxyfluorfen [24] and acifluorfen-sodium [25], Replacement of the chlorine with a trifluoromethyl group resulted in a dramatic increase in the herbicidal properties of these compounds, in terms of both potency and the spectrum of weeds controlled. 

M. Matringe, J.M. Camadro, R. Labbe, R. Scalla, Protoporphyrinogen oxidase as a molecular target for diphenyl ether herbicides, Biochem. J. 260 (1989) 231-235. 

Many photobleaching herbicides act by inhibiting the enzyme protoporphyrinogen oxidase (Protox), which catalyzes the last step in common between chlorophyll and heme biosynthesis. Usnic acid shares some structural features in common with these herbicides, such as the diphenyl ether scaffolding. The inhibitory activity of (-)-usnic acid on Protox was similar to that of the herbicide, acifluorfen, (I50 ca. 3 pM). However, these compounds did not displace acifluorfen from its binding site on Protox (data not shown), indicating that this natural product interacts with Protox differently than other photobleaching inhibitors. 

Protoporphyrinogen oxidase inhibtor leading to membrane disruption... 

Protoporphyrinogen oxidase inhibitor (Chlorophyl biosynthesis pathway)... 

Figure 4. Effect of the synthetic diphenyl ether acifluorfen (triangles), the natural diphenyl ether fungal metabolite cyperine (squares) and the dibenzofurandione lichen metabolite usnic acid (circles) on the activity of protoporphyrinogen oxidase. The dotted line represents 50% inhibition of enzyme activity.

Figure 3 The synthesis of heme from glycine and sucdnyl-CoA. The enzymes are ALAS, S-aminolevulinic acid (ALA) synthase ALAD, S-aminolevulinic acid dehydratase PBGD, porphobilinogen deaminase UROIIIS, uroporphyrinogen III synthase UROD, uroporphyrinogen decarboxylase CPO, coproporphyrinogen oxidase PPO, protoporphyrinogen oxidase and FECH, ferrochelatase.

Protoporphyrinogen oxidase converts protoporphyrinogen IX to the fully desaturated porphyrin in a reaction that uses O2 as the terminal electron acceptor (Fig. 3). The crystal structure of the homodimeric enzyme shows it has one FAD per monomer, which presumably mediates the porphyrin oxidation reaction (19). Like the decarboxylation mediated by coproporphyrinogen oxidase, this reaction also occurs in the mitochondrion. Mutations in the protoporphyrinogen oxidase gene are responsible for variegate porphyria (21). Acute attacks of this disease can be effectively treated by intravenous administration of hematin. 

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