Heme

ALAS and PLP

Evolution of these regions may have played a role in alterations of PLP binding and its regulation for ALAS to play specific roles in adaptation of heme synthesis to cell-specific contexts. As PLP is generally maintained at a low concentration in the cell (Hamfelt, 1967; Cheung et al., 2003), and its spontaneous conjugation to apoALAS is slow (Kardon et al. 2015), it is likely that vertebrate ALAS requires other, yet to be discovered chaperones that facilitate PLP incorporation to form the holoenzyme. (R1)

FECH

Complex with MFRN1 and ABCB10

FECH is also in complex with MFRN1 and ABCB10, facilitating the transfer of ferrous iron to FECH for heme synthesis (R1)

FAM210B

The presence of FAM210B, a protein that is upregulated by during erythroid differentiation, is also required for maximal FECH activity in differentiating erythroid cells, even though it is not required for maintenance of FECH protein levels. …. While FAM210B is necessary for the optimal activity of soluble FECH, the regulation of FECH by FAM210B is even more profound when the mitochondrial membranes are intact, as FAM210B interacts with PPOX and FECH, and is necessary for maximal import of iron into the mitochondria during erythroid differentiation and is proposed to facilitate the interaction between MFRN1 and FECH (R1)