Pyruvate carboxylase (PC) is a mitochondrial enzyme catalyzing the ATP-dependent carboxylation of pyruvate to oxaloacetate (1). This is a central biochemical reaction controlling whole-body energetics (2). It is the first step of gluconeogenesis and the main anaplerotic reaction to replenish tricarboxylic acid (TCA) cycle intermediates. Additionally, it is involved in e.g. lipogenesis or insulin secretion.
PC shows high expression in liver and kidney, the primary organs of gluconeogenesis, which synthesize and export glucose into the bloodstream (3).
In the brain, PC plays a critical anaplerotic role during metabolism as well. It is predominately expressed in astrocytes and is needed for the de novo synthesis of glutamate, the main excitatory neurotransmitter (see Featured Topic The Glutamatergic Synapse). Recent literature indicates that PC is also expressed in a subpopulation of neurons (4). There is evidence that gluconeogenesis exists in brain astrocytes (5) and this is becoming more recognized as an important alternative glucose source for neurons, specifically in ischemic stroke and brain tumors. PC has been associated with metabolic reprogramming of cancer cells and tumor progression in a variety of cancer models (2).