RESUMEN
This review examines the evidence suggesting that the anaerobic biosynthesis of cobalamin (vitamin B12) evolved during early stages of cell evolution and was quickly recruited in the pathway leading to deoxyribonucleotides, the building blocks of DNA genomes. Biochemical evolution preceding the synthesis of the heme group and related molecules is discussed within the framework of geological evolution in which the appearance and accumulation of an oxygen-rich atmosphere stands as one of the major events in the evolution of the planet and the biosphere.
Asunto(s)
Corrinoides/metabolismo , Hemo/metabolismo , Animales , Corrinoides/genética , ADN/genética , ADN/metabolismo , Evolución Molecular , Evolución Planetaria , Hemo/genética , Humanos , Vitamina B 12/genética , Vitamina B 12/metabolismoRESUMEN
1. Unsaturated vitamin B12-binding protein was isolated from sow's milk whey by affinity chromatography on a vitamin B12-Sepharose column with a yield of 54% (3920-fold purification). The purified binding protein was homogeneous by the criteria of polyacrylamide gel electrophoresis and high speed sedimentation equilibrium. 2. The isolated vitamin B12-binding protein was a glycoprotein with 24% carbohydrates (fucose, galactose, mannose, galactosamine, glucosamine and sialic acid) and high levels of aspartic and glutamic acids. The protein which has a molecular weight of 61,800 determined by ultracentrifugation, consisted of a single polypeptide chain, bound vitamin B12 on an equimolar basis and had a partial specific volume of 0.697 ml/g (mechanical oscillator technique). 3. Its dissociation constant, Kd, for cyanocobalamin was 8.8 x 10(-10)M. The binding protein showed similar affinities for hydroxo-, methyl-, and adenosylcobalamin when compared to cyanocobalamin relative affinity ratios, but lower affinities (31-49%) for cobinamide, Co-alpha-[adenyl] cobamide and Co-alpha-[2-methyl-adenyl] cobamide. Therefore, the substitution of the axial ligand to the cobalt atom in the corrin ring of vitamin B12 had no effect on affinity, whereas the differences in the nucleotide part of the molecule caused a small decrease in energy of the interaction. 4. The present results indicate close similarity of the vitamin B12-binding protein from sow's milk to vitamin B12-binding proteins from other sources, especially those from human milk and from porcine gastric mucosa (nonintrinsic factor). Whether this similarity extends to antigenic and physiological properties remains to be investigated.