Biosynthesis of the pigments of life

Many vitally im portan t functions in living systems are carried out by metal ions held as complexes within organic ligands, the organic p a rt of the molecule being a te trapyrrolic macrocycle. Chlorophyll, haemoglobin, the cytochromes and vitam in B12 all fall into this family of ‘pigm ents of life’, a list th a t emphasizes their central im portance in living systems. Research on the biosynthesis of these pigm ents has involved the synergistic com bination of synthesis, structure determ ination, carbon nuclear magnetic resonance and isotopic labelling with radioactive and stable isotopes in conjunction with enzymology and kinetics. The lecture describes the logical series of experim ents based on these approaches which have led to a step-by-step knowledge of the biosynthesis of the parent macrocycle (uroporphyrinogen-III) from which the other pigm ents are derived. One main pathw ay from the parent macrocycle involves oxidative transform ations and leads eventually to protohaem required inter alia for haemoglobin and myoglobin. The second im portan t pathw ay makes use of C-m ethylation to convert the parent macrocycle through many stages finally into vitam in B 12. The biosynthetic studies on vitam in B 12 are outlined with particular emphasis on the use of isotopic labelling with both radioactive and stable isotopes of carbon and hydrogen. Roughly tw o-thirds of the entire biosynthetic pathw ay to vitam in B12 has now been elucidated. The scarcity of several of the known interm ediates on the pathw ay severely hampers future researches and progress tow ards the to tal synthesis of these key materials is reviewed. Finally, the lecture brings out the evolutionary interest of w hat has been discovered about the biosynthesis of the pigments of life.