PC

The PC gene provides instructions for making an enzyme called pyruvate carboxylase. This enzyme is active in mitochondria, which are the energy-producing centers within cells.

Pyruvate carboxylase is responsible for a chemical reaction that converts a molecule called pyruvate to another molecule called oxaloacetate. This reaction is essential for several different cellular functions. In the kidneys and liver, it is the first step in a process called gluconeogenesis. Gluconeogenesis generates glucose, a simple sugar that is the body's main energy source. This chemical reaction also occurs in the pancreas, where it helps regulate the secretion of a hormone called insulin. Insulin controls the amount of glucose in the blood that is passed into cells for conversion to energy.

In fat-storing (adipose) tissue, pyruvate carboxylase is involved in the formation of certain fats (lipogenesis). This enzyme also plays an important role in the nervous system, where it replenishes the building blocks needed to make brain chemicals called neurotransmitters. Additionally, pyruvate carboxylase is necessary for the formation of myelin, which is the fatty covering that insulates and protects certain nerve cells.

pyruvate carboxylase deficiency - caused by mutations in the PC gene

Only a few mutations in the PC gene have been identified in people with pyruvate carboxylase deficiency. Some of these mutations change a single protein building block (amino acid) in pyruvate carboxylase, which may reduce the amount of this enzyme in cells or disrupt its ability to effectively convert pyruvate to oxaloacetate. Other genetic changes lead to the production of an abnormally short version of the enzyme that is completely nonfunctional.

If pyruvate carboxylase is missing or altered, it cannot carry out its role in generating glucose. Any disruption in gluconeogenesis impairs the body's ability to make energy in mitochondria. Additionally, a loss of pyruvate carboxylase allows potentially toxic compounds such as lactic acid and ammonia to build up and damage organs and tissues. Researchers suggest that the loss of pyruvate carboxylase function in the nervous system, particularly the role of the enzyme in myelin formation and neurotransmitter production, also contributes to the neurologic features of pyruvate carboxylase deficiency.