Nature's pathways to the pigments of life

Abstract

This article is based on the Robert Robinson Lecture that was delivered on 10th April 1986 at the Annual Congress of The Royal Society of Chemistry, at the University of Warwick 1 Introduction 2 The Biosynthesis of Uroporphyrinogen 111 3 First Studies on the Stereochemistry of Action of 4 The Mechanism of Action of Cosynthetase 5 The Biosynthesis of Vitamin B,, 6 Acknowledgements 7 References Deaminase ' Enzyme Nomenclature 1984 ') for deaminase is porphobilinogen deaminase [E.C. 4.3.1.81 (the previous recommended name was hydroxymethylbilane synthase) and that for cosynthetase is uroporphyrinogen-111 synthase [E.C. 4.2.1.751. NPR 4 6 * The parent macrocycle which appears (in a highly substituted form) in cobyrinic acid (22) is called corrin.

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…The total synthesis of chlorophyll-a (5) conducted by Woodward constitutes one of the most prominent achievements in organic chemistry [27]. This, and several related pigments, is biosynthesized from the common building block porphobilinogen (6) [28][29][30]. Likewise, the amino acid L-proline is ubiquitous in biologically important peptides and proteins, as well as other natural products.…”

Computational Design of Four-Helix Bundle Proteins That Bind Nonbiological Cofactors

“…Porphyrinic cofactors such as hemes and chlorophylls are also essential in fundamental biological energy conversion processes such as photosynthesis and cellular respiration (21). These and other tetrapyrrolic compounds have been called the "pigments of life" (22)(23)(24)(25). The versatility of heme-and other porphyrin-containing proteins draws upon several features: the delocalized π-conjugated porphyrin macrocycle, the multiple oxidation states of the central metal ion, the amino acid residues that coordinate the metal ion, and the residues near the cofactor.…”

The biosynthesis of porphyrins, chlorophylls, and vitamin B12

“…The next step is thought to be a reduction to give glutamate 1semialdehyde (2), catalysed by a NAD(P)H-dependent dehydrogenase. This is the step in the pathway that is sensitive to feedback inhibition by haem,29*30 although it has been concluded from the results of a study of Chlamydomonas mutants that the synthesis of ALA is also controlled by repression of the synthesis of the enzymes.…”

“…This is the step in the pathway that is sensitive to feedback inhibition by haem,29*30 although it has been concluded from the results of a study of Chlamydomonas mutants that the synthesis of ALA is also controlled by repression of the synthesis of the enzymes. 33 The glutamate 1semialdehyde (2) that is produced has again been identified chromatographically with synthetic material and synthetic (2) has also been reported to be converted into ALA by the enzyme However, there is some dispute as to the identity of the synthetic material, as it is claimed that (2) is extremely unstable and cannot be isolated before it undergoes polymeri ~a t i o n . ~~ The last step in the pathway in Scheme 2 is an intramolecular transamination reaction and has been observed to be inhibited in v i m by the common pyridoxal-directed inhibitor gabaculine.…”