Deoxyribonucleotide Synthesis and the Role of Vitamin B12 in Erythropoiesis

Abstract

Publisher Summary This chapter reviews the current knowledge of the several pathways of deoxyribonucleotide synthesis in bacteria and animal cells other than bone marrow and discusses the available evidence bearing on the pathway in human bone marrow. Current knowledge of the pathways of deoxyribonucleotide synthesis has been derived mainly from studies in two strains of bacteria—Escherichia coli, species lacking a nutritional requirement for vitamin B12 and Lactobacillus leichmannii, a nutritional vitamin B12 auxotroph. The system from E. coli utilizes ribonucleoside diphosphates as substrates; and L. leichmannii reduces ribonucleoside triphosphates. The more striking difference between the two enzyme systems is the fact that the enzyme from L. leichmannii, but not that from E. coli, has an absolute requirement for the vitamin B12 coenzyme, 5,6-dimethylbenzimidazolyl 5′-deoxyadenosine cobamide (DBCC). The ribonucleotide reductases from Novikoff hepatoma cells and E. coli have some properties in common that distinguish them from the corresponding enzyme of L. leichmannii, including (1) the preferred substrate is a ribonucleoside diphosphate, (2) no requirement for a cobamide coenzyme has been demonstrated, (3) an absolute requirement for Mg++, and (4) similar patterns of allosteric effects, among which is an inhibitory effect of deoxyadenosine triphosphate on the reductions of all four ribonucleotides.