I'm a PC (Pyruvate Carboxylase)…and diabetes was not my idea!

Abstract

NIH estimates that 23 million Americans have diabetes, and 6.2 million are undiagnosed. If untreated, diabetes can cause complications, including heart disease and neuropathy. Type two diabetes patients cannot regulate glucose due to insulin resistance or deficiency. Pyruvate carboxylase (PC) plays an important role in insulin release from pancreatic β cells. Abnormal PC activity has been correlated with type two diabetes. PC is a dimer of dimers, each monomer a single chain with four domains: N‐terminal biotin carboxylase (BC), central carboxyltransferase (CT), C‐terminal biotin carboxyl carrier protein (BCCP), and allosteric domains. PC catalyzes the conversion of pyruvate to oxaloacetate (OAA). The process begins when biotin is carboxylated at the BC active site. The BCCP domain transfers the carboxybiotin to an active site in the CT domain. OAA is formed at the CT domain by adding a carboxyl group to pyruvate. Researchers concluded that the BCCP domain swings between active sites on opposite chains, instead of sites on the same chain. The Brown Deer SMART Team (Students Modeling A Research Topic), in collaboration with MSOE, built a model of PC using 3D printing technology illustrating this movement of the BCCP domain. Current research is focused on increasing PC activity through controlling a binding site in the allosteric domain, which may increase insulin production.Supported by a grant from NIH‐NCRR‐SEPA.