Vitamin B12-dependent enzymes and transport proteins

Vitamin B12-dependent enzymes and transport proteins constitute a critical metabolic and physiological system responsible for the absorption, systemic transport, and intracellular utilization of cobalamin (Vitamin B12) [2, 6]. In humans, this system includes two primary enzymes: methionine synthase (MTR), which facilitates the conversion of homocysteine to methionine in the cytoplasm, and methylmalonyl-CoA mutase (MUT), which converts methylmalonyl-CoA to succinyl-CoA in the mitochondria [1, 2]. The transport pathway involves a series of specialized proteins, including haptocorrin, intrinsic factor (IF), and transcobalamin II (TCII), along with their respective receptors like cubilin and CD320 [2, 6, 7]. These proteins ensure that B12 is protected from degradation in the gastrointestinal tract and efficiently delivered to peripheral tissues [5, 6]. Dysregulation or deficiency in any component of this system leads to severe clinical conditions such as pernicious anemia, megaloblastic anemia, and various inborn errors of metabolism characterized by elevated homocysteine or methylmalonic acid [3, 4, 7]. Therapeutically, these proteins are targeted through cobalamin supplementation to treat deficiencies, while their overexpression in certain cancers is being explored for targeted drug delivery and diagnostic imaging [3, 5].

Other names

Cobalamin-dependent enzymesCobalamin transport proteinsB12-binding proteinsVitamin B12 metabolic pathwayCobalamin metabolism and transport system

Drugs targeting this system primarily act through cofactor replacement to restore enzymatic activity in deficiency states [2, 7], or through the inhibition of specific components, such as the irreversible inactivation of methionine synthase by nitrous oxide [1]. Additionally, the high affinity of transport proteins and receptors for cobalamin is exploited in oncology for the targeted delivery of cytotoxic agents or imaging labels to tumor cells overexpressing these proteins [3, 5].