4 - Cobalamin binding proteins and their receptors

Summary

Introduction

Mammalian cobalamin binding proteins include those proteins that bind cobinamides. All molecules containing four reduced pyrrole rings linked together (called ‘corrin’ because they are at the core of the molecule) are called corrinoids. The prefix ‘cob’ is used when a cobalt atom is present, and such corrinoids are termed cobinamides. The cobinamides that show biological activity in microorganisms and/or mammals are called vitamin B₁₂ and those that are active only in human and mammalian metabolism are called cobalamins. The two naturally occurring forms of cobalamin (cbl) in man are methyl-cobalamin (found mostly in the cytoplasm) and adenosylcobalamin (found in mitochondria). Cobinamides used by bacteria lack the ribosyl, aminopropanol, or nucleotide groups of cobalamin, or contain substitutions on these moieties (Hogenkamp, 1975).

The cobalamin binding proteins are three in number, each with a different membrane receptor that identifies the cell that subserves the function of the binding protein. Intrinsic factor (IF) refers to a protein secreted by the stomach which mediates the transepithelial absorption of cbl in the ileum (Allen, 1975). Haptocorrins comprise a group of immunologically identical proteins produced in a variety of body fluids (plasma, milk, amniotic fluid, saliva) from many cell types (granulocytes, mammary gland, salivary duct and acinar cells) (Nexo et al., 1985; Grasbeck et al., 1962). These proteins were formerly referred to as R protein (for rapid electrophoresis) or non-intrinsic factor (Stenman, 1975a).