Labile heme pool (LHP)

The labile heme pool (LHP) refers to the small, transient fraction of intracellular heme that is not sequestered within hemoproteins. This pool serves as a critical regulatory and signaling reservoir, providing bioavailable heme for the maturation of newly synthesized hemoproteins and modulating the activity of various transcription factors and enzymes, such as Bach1 and ALAS1. In healthy cells, the LHP is maintained at low concentrations to prevent the pro-oxidant and cytotoxic effects of free heme, which can catalyze the formation of reactive oxygen species (ROS) via the Fenton reaction. Dysregulation of the LHP is central to the pathogenesis of several diseases; for instance, malaria parasites must detoxify heme released from hemoglobin, and drugs like chloroquine act by disrupting this process to increase toxic labile heme levels. Conversely, in porphyrias, exogenous hemin is administered to replenish the regulatory heme pool and suppress the overproduction of toxic precursors.

Other names

Regulatory heme poolFree heme poolHeme poolNon-protein-bound hemeBioavailable hemeIntracellular heme pool

Inhibition of heme crystallization, feedback inhibition of ALAS1, and inhibition of heme oxygenase.