Vanadyl sulfate (Fig. 1 is the chemical structure of vanadyl sulfate) is a compound consumed by athletes and bodybuilders to enhance muscular strength and development. The biochemical function of vanadyl sulfate in the human body is not completely understood, yet a great deal of attention has been paid to this compound due to its ability to mimic insulin. Although all of the molecular details concerning vanadyl sulfate as an insulin mimic are unclear some aspects have been elucidated as described below.
After ingestion of vanadyl sulfate, vanadyl is further oxidized into vanadate (Fig. 2 is the chemical structure of vanadate) which competitively inhibits the protein tyrosine phosphatase 1B (PTP1B). PTP1B negatively regulates insulin function by dephosphorylating and inactivating the insulin receptor (Fig. 3 schematically shows how vanadate inhibition of PTP1B stimulates the function of insulin leading to glucose influx into the cell via the glucose transporter GLUT4). During the PTP1B catalyzed dephosphorylation reaction the catalytic cysteine residue’s sulfur atom nucleophilically attacks the phosphate group from the insulin receptor’s phosphotyrosine residue leading to dephosphorylation (Fig. 4 shows the dephosphorylation reaction catalyzed by PTP1B). The transition state during this reaction is a pentacovalent intermediate (Fig. 5 depicts the pentacovalent transition state intermediate) that is structurally mimicked by vanadate (Fig 6 illustrates vanadate bound in the active site of PTP1B near the catalytic cysteine residue). This makes vanadate an excellent competitive inhibitor of PTP1B preventing the insulin receptor’s phosphotyrosine binding and dephosphorylation as enzyme’s like PTP1B preferably bind the transition state in order to lower the free energy of activation promoting catalysis. Consequently vanadate inhibition of PTP1B enhances insulin activity increasing the conversion of glucose into energy (ATP) for greater athletic performance.
