Many chromatin-modifying enzymes use common metabolites as cofactors, but the connections between central metabolism and epigenetics remain poorly explored. The link between NAD+ levels and sirtuin function has been well established, but recent work for our lab has uncovered an unanticipated depth in the links between metabolism and epigenetics. We found that disruption of an early step in the pentose phosphate pathway affected heterochromatin stability in a spatially heterogeneous manner within yeast colonies. This spatial heterogeneity in silencing likely reflects spatial heterogeneity in metabolism within yeast colonies. The pentose phosphate pathway is a major source of both five carbon sugars and NADPH. Here, we present evidence that it is the cellular NADPH levels that affect the stability of heterochromatin at the yeast silent mating locus HML.