IDO1 and hyperinsulinemic hypoglycemia, familial, 4: Both TDO2 and IDO require heme for catalytic activity and cyclical restoration of TDO2 and IDO catalysis by heme availability would be expected to lead to markedly increased flux through the kynurenine pathway stemming from upregulation of the enzyme monomer synthesis as a compensatory mechanism during the heme deficiency phase, as observed by Wetterberg et al. [155] in an animal model.