Vitamin-B(12) is a generic term for corrinoid compounds that exhibit the
biological activity of
cyanocobalamin and are collectively referred to as
cobalamins.
Methylcobalamin and 5-deoxyadenosylcobalamin are the active
cobalamins in human metabolism.
Cobalamin plays a crucial role in the maintenance of
homocysteine and
methylmalonyl-CoA homeostasis and is required for erythrocyte formation and
DNA synthesis. Data from human and animal studies indicate that
cobalamin deficiency impairs neuronal function; a process that is thought to contribute to age-related
cognitive decline and
dementia.
Cobalamin deficiency also results in dysfunction of the peripheral nervous system; among other disorders. Although there is a detailed understanding of the biochemical pathways that are perturbed in
cobalamin deficiency, the mechanisms underlying age-related dyshomeostasis in such pathways remain to be addressed. Because
cobalamin utilization is dependent on its efficient transit through lysosomes, and mounting evidence indicates that lysosomal function deteriorates in aging long-lived post-mitotic cells such as neurons, in the present article we review published data that supports the proposition that impaired lysosomal processing of
cobalamin may play a significant role in age-related (neuro) degenerative diseases.