Ligandin: review and update of a multifunctional protein

Abstract

Ligandin is an abundant soluble protein of relatively short half life which is induced by many drugs and chemicals and stabilized in the absence of thyroid hormone. The protein is strategically concentrated in cells associated with transport and detoxification of a large variety of potential endogenous ligands such as bilirubin and perhaps heme, and exogenous, such as a multitude of drugs and chemicals. The protein is a dimer in rat liver. Whether it is a primary gene product or whether at least two genes are involved is not known. The protein has broad, low affinity catalytic activity for ligands having electrophilic groups and hydrophobic domains. It either catalyzes formation of GSH conjugates (e.g. bromosulphophthalein), noncovalently binds prior to biotransformation or excretion in bile (e.g. bilirubin), or covalently binds (e.g. activated carcinogens) potential ligands. Recent studies expand the scope of ligandinology to include its possible role in chemical carcinogenesis, diagnosis of inflammatory and neoplastic disease of the liver and kidney, and participation in intracellular transport. Although some of the roles that have been outlined are speculative, any single function is important. These are primitive enzymes and nonspecific binding proteins but "it is precisely their simplistic design that allows such protein serviceability".