{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Bisphosphoglycerate mutase (BPGM) plays a central role in modulating oxygen delivery by catalyzing the conversion of 1,3‐bisphosphoglycerate to 2,3‐bisphosphoglycerate (2,3‐BPG), a key effector that decreases hemoglobin’s oxygen affinity. Recent studies have demonstrated that in the placenta, BPGM is expressed in labyrinthine trophoblasts where its activity influences maternal circulating 2,3‐BPG levels, thereby enhancing oxygen release to the developing fetus and potentially contributing to fetal growth regulation under conditions of growth restriction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In a related context, alterations in BPGM—including genetic variants—have been linked to familial erythrocytosis by modifying hemoglobin–oxygen interactions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, aberrant BPGM expression appears to extend beyond classical oxygen transport. Proteomic analyses in respiratory syncytial virus (RSV) infection have revealed significant upregulation of BPGM in conjunction with increased glycolytic activity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while studies in steroid-induced osteonecrosis of the femoral head have identified BPGM as a potential serum biomarker—a finding that may reflect its roles in regulating erythrocyte function and immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Developmental studies indicate that BPGM expression distinguishes in vivo from in vitro conditions during early embryogenesis; notably, while hemoglobin subunits are predominantly expressed in vivo, BPGM is expressed at higher levels in in vitro–derived human embryos, suggesting a compensatory or regulatory mechanism for oxygen homeostasis during early development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, dynamic changes in BPGM transcript levels have been observed in rodent models of contextual fear conditioning, hinting at a broader role of metabolic reprogramming in neuronal tissue."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond mammalian systems, members of the d‐PGMase superfamily—which include BPGM homologues—have been implicated in carbohydrate metabolism in plants, where overexpression studies reveal impacts on glucose uptake and partitioning."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, systems‐level metabolic analyses in human erythrocyte enzymopathies underscore that altered BPGM flux can significantly affect red blood cell metabolic homeostasis, thereby contributing to the pathogenesis of metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight the multifaceted functions of BPGM—from fine‐tuning oxygen delivery via modulation of hemoglobin affinity to participating in broader metabolic adaptations in both physiological and pathological settings.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M Gu, D C Pritlove, C A R Boyd, et al. 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