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PIMT and RBC metabolism
in gene expression (e.g., transcription factors and/or enzymes involved in post-translational modification) as a result of unrepaired oxidation of aspartate and/or asparagine, which then changes the baseline genetic expression of enzymes involved in metabolic pathways. However, this explanation would only apply to nucleated cells, and not mature RBC. Given that the same general changes were seen in both RBC and other organs, this hypothesis is not favored as a general mechanism. A third
AB
and even less likely hypothesis, but one we cannot formal- ly rule out based upon existing data, is that PIMT has addi- tional enzymatic activities that have not yet been identi- fied. The exact mechanism(s) by which PIMT activity broadly affects metabolism will require further investiga- tion to elucidate; however, the findings in this manuscript demonstrate that PCMT1 is required for a number of dis- tinct metabolic pathways and is essential for RBC to sur- vive oxidative stress.
C
Figure 6. Metabolomics of phenylhydrazine-treated red blood cells from bone marrow-trans- planted wild-type and PCMT1-/- knockout x Ubi-GFP.B6 chimerae. (A) Metabolomics of PHZ- treated red blood cells (RBC) from bone marrow-transplanted wild-type (WT) and PCMT1-/- knockout (PCMT1 KO) x Ubi-GFP.B6 chimerae; (B) a significant increase in the percentage of clearance of PCMT1 KO RBC was noted following injection of phenylhydrazine (PHZ) in vivo; (C) this phenotype was accompanied by significant metabolic alterations in the PCMT1 KO RBC.
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