N. Evans

Bio: N. Evans is an academic researcher from Cardiff University. The author has contributed to research in topics: Porphyrinogens & HEXA. The author has an hindex of 4, co-authored 5 publications receiving 269 citations.

Macrocyclic intermediates in the biosynthesis of porphyrins.

Abstract: The hepta-, hexa- and penta-carboxylic porphyrins found in the faeces of rats poisoned with hexachlorobenzene have been separated by high-pressure liquid chromatography and characterized largely by spectroscopie methods. Their structures were confirmed by total synthesis, as part of a programme in which eleven of the fourteen hepta-, hexa- and penta-carboxylic porphyrins derived from uroporphyrin III have now been synthesized as their methyl esters. The four isomeric heptacarboxylic and three of the pentacarboxylic porphyrinogens have been incubated with haemolysates of chicken erythrocytes, and they are all converted into protoporphyrin IX but at different rates. On the basis of this and other evidence we conclude that the decarboxylation of uroporphyrinogen III to coproporphyrinogen III is a stepwise process taking place by a preferred pathway (both in normal and abnormal metabolism); the acetic acid groups are decarboxylated in a sequential clockwise fashion starting with that on the D ring and followed by those on the A, B and C rings. In the poisoned rats the uroporphyrinogen decarboxylase enzyme (or group of enzymes) is probably partially inhibited and the pentacarboxylic porphyrinogen with an acetic acid group on ring C accumulates. The latter is then transformed by a side pathway into dehydroisocoproporphyrinogen and thence into dehydroisocoproporphyrin and its congeners.

Hepta- and hexa-carboxylic porphyrinogen intermediates in haem biosynthesis.

Abstract: In the course of our studies on intermediates in normal and abnormal metabolism of porphyrins we have synthesised a number of porphyrins related to uroporphyrin-III and compared them with materials isolated from natural sources. In the present paper we show that the corresponding porphyrinogens are all metabolised to protoporphyrin-IX by haemolysates of chicken erythrocytes, but at different rates. The results are discussed in relation to our conclusions concerning the preferred pathway of degradation of uro'gen-III to coproporphyrinogen-III, which indicate a clockwise sequence of decarboxylation reactions.

Pentacarboxylic intermediates in haem biosynthesis.

Abstract: The incorporation of the four possible type III porphyrinogens into protoporphyrin is described and their various rates or conversion are discussed. The techniques used involved the incubation of the porphyrinogens in chicken red cell haemolysates followed by extraction and characterisation of the end products on HPLC and TLC. Porphyrin 5 b c d was shown to be more slowly incorporated than porphyrins 5 a b d, 5 a c d and 5 a b c. The relevance of these findings to an understanding of the porphyrin excretion pattern in hepato-erythrocitic porphyria is considered.

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.

Tetrapyrrole Metabolism in Arabidopsis thaliana.

Abstract: Higher plants produce four classes of tetrapyrroles, namely, chlorophyll (Chl), heme, siroheme, and phytochromobilin. In plants, tetrapyrroles play essential roles in a wide range of biological activities including photosynthesis, respiration and the assimilation of nitrogen/sulfur. All four classes of tetrapyrroles are derived from a common biosynthetic pathway that resides in the plastid. In this article, we present an overview of tetrapyrrole metabolism in Arabidopsis and other higher plants, and we describe all identified enzymatic steps involved in this metabolism. We also summarize recent findings on Chl biosynthesis and Chl breakdown. Recent advances in this field, in particular those on the genetic and biochemical analyses of novel enzymes, prompted us to redraw the tetrapyrrole metabolic pathways. In addition, we also summarize our current understanding on the regulatory mechanisms governing tetrapyrrole metabolism. The interactions of tetrapyrrole biosynthesis and other cellular processes including the plastid-to-nucleus signal transduction are discussed.