R.J. Porra

Bio: R.J. Porra is an academic researcher. The author has contributed to research in topics: Protoporphyrin. The author has an hindex of 1, co-authored 1 publications receiving 28 citations.

Structure and function of enzymes in heme biosynthesis.

Abstract: Tetrapyrroles like hemes, chlorophylls, and cobalamin are complex macrocycles which play essential roles in almost all living organisms. Heme serves as prosthetic group of many proteins involved in fundamental biological processes like respiration, photosynthesis, and the metabolism and transport of oxygen. Further, enzymes such as catalases, peroxidases, or cytochromes P450 rely on heme as essential cofactors. Heme is synthesized in most organisms via a highly conserved biosynthetic route. In humans, defects in heme biosynthesis lead to severe metabolic disorders called porphyrias. The elucidation of the 3D structures for all heme biosynthetic enzymes over the last decade provided new insights into their function and elucidated the structural basis of many known diseases. In terms of structure and function several rather unique proteins were revealed such as the V-shaped glutamyl-tRNA reductase, the dipyrromethane cofactor containing porphobilinogen deaminase, or the “Radical SAM enzyme” coproporphyrinogen III dehydrogenase. This review summarizes the current understanding of the structure–function relationship for all heme biosynthetic enzymes and their potential interactions in the cell.

Porphyrin Accumulation and Export by Isolated Barley (Hordeum vulgare) Plastids (Effect of Diphenyl Ether Herbicides).

Abstract: We have investigated the formation of porphyrin intermediates by isolated barley (Hordeum vulgare) plastids incubated for 40 min with the porphyrin precursor 5-aminolevulinate and in the presence and absence of a diphenylether herbicide that blocks protoporphyrinogen oxidase, the enzyme in chlorophyll and heme synthesis that oxidizes protoporphyrinogen IX to protoporphyrin IX. In the absence of herbicide, about 50% of the protoporphyrin IX formed was found in the extraplastidic medium, which was separated from intact plastids by centrifugation at the end of the incubation period. In contrast, uroporphyrinogen, an earlier intermediate, and magnesium protoporphyrin IX, a later intermediate, were located mainly within the plastid. When the incubation was carried out in the presence of a herbicide that inhibits protoporphyrinogen oxidase, protoporphyrin IX formation by the plastids was completely abolished, but large amounts of protoporphyrinogen accumulated in the extraplastidic medium. To detect extraplastidic protoporphyrinogen, it was necessary to first oxidize it to protoporphyrin IX with the use of a herbicide-resistant protoporphyrinogen oxidase enzyme present in Escherichia coli membranes. Protoporphyrinogen is not detected by some commonly used methods for porphyrin analysis unless it is first oxidized to protoporphyrin IX. Protoporphyrin IX and protoporphyrinogen found outside the plastid did not arise from plastid lysis, because the percentage of plastid lysis, measured with a stromal marker enzyme, was far less than the percentage of these porphyrins in the extraplastidic fraction. These findings suggest that of the tetrapyrrolic intermediates synthesized by the plastids, protoporphyrinogen and protoporphyrin IX, are the most likely to be exported from the plastid to the cytoplasm. These results help explain the extraplastidic accumulation of protoporphyrin IX in plants treated with photobleaching herbicides. In addition, these findings suggest that plastids may export protoporphyrinogen or protoporphyrin IX for mitochondrial heme synthesis.

The enzymic conversion of coproporphyrinogen III into protoporphyrin IX

Abstract: animals moving to high altitudes and thus the stimulation of uroporphyrinogen formation would be small. Nevertheless, it is known that increased haemopoiesis on acclimatization to high altitude is a slow process (cf. Grant & Root, 1952), and small changes in the rate of porphyrin synthesis, maintained for several weeks, could well lead to the observed blood haemoglobin concentrations. Krebs (1959) has pointed out that, though biochemical and hormonal control mechanisms both operate in higher animals, metabolic regulation at the biochemical level assumes great importance in bacteria, which contain no hormones. It is thus conceivable that the regulation by oxygen of haem biosynthesis, described above, may play a part in the changes in haemoprotein concentrations during respiratory adaptation in micro-organisms. Using Aerobacter aerogenes, Moss (1956) has shown that the maximum cell content of cytochrome a2 is obtained when the oxygen concentration in the bacterial culture during growth is 1 ,uM. Above and below this concentration the cytochrome a2 content of the cell falls off in a manner similar to that found for protohaem formation in vitro (Falk et al. 1959).