Vitamin B12 and Folic Acid

Introduction

• The two maturation factors — Vitamin B₁₂ (cobalamins) and folic acid (pteroylglutamic acid) are the B-group "maturation factors" whose deficiency produces megaloblastic anaemia — large red-cell precursors in marrow and large, short-lived progeny in blood.
• Shared final lesion — The basic defect in both is impaired DNA synthesis; because they are metabolically interlinked, the anaemia of either is morphologically indistinguishable — the same block in thymidylate/DNA synthesis reached by two routes.
• Nucleo-cytoplasmic asynchrony — Defective nuclear (chromosomal) division with near-normal cytoplasmic maturation → abnormal cells, intramedullary cell death and ineffective haematopoiesis; severe deficiency affects all cell lines → pancytopenia, plus damage to other high-turnover tissues (GI mucosa).
• Historical threads — Minot & Murphy (1926) — dietary liver reverses pernicious anaemia; Castle — an extrinsic factor (diet) + intrinsic factor (stomach) give the haemopoietic principle (B₁₂, isolated 1948). Wills' factor — a macrocytic anaemia in Indian women responding to crude liver extract but not the purified anti-pernicious fraction — proved to be folic acid.