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                                                                                                                                                         Fig. 1. Metabolic reprogramming during mastitis and the role of PFKFB3.
             Image Source: Laboratorios LABIS
























                                                                                                                                                         Mastitis has long been seen   mitochondria, thereby
                                                                                                                                                         as an infectious disease. New   supporting elevated
                                                                                                                                                         research shows it is also a   glycolytic flux in proliferating
                                                                                                                                                         metabolic disorder. During   or metabolically active cells.
                                                                                                                                                         infection, immune and     In mastitis, HK activity is
                                                                                                                                                         mammary epithelial cells   increased to secure a
                                                                                                                                                         shift from oxidative      continuous supply of
                                                                                                                                                         metabolism to aerobic
                                                                                                                                                         glycolysis —a rapid but less
            Mastitis and Metabolism:                                                                                           pathways highlight the    efficient method of
                                                                                                                                                         generating energy. This is
                                                                                                                               immune metabolic basis of
            The Overlooked Connection                                                                                          bovine infectious diseases.   similar to the Warburg effect
                                                                                                                                                         described in cancer cells
                                                                                                                               Integrating these insights
                                                                                                                                                         (O'Neill et al., 2016).
                                                                                                                               with epitope mapping for
            “During mastitis, immune cells accelerate glycolysis to support                                                    diagnostic development,   Glycolysis on overdrive:
            defence, while invading bacteria exploit host metabolism to                                                        along with the design of   HKII, PFKP, and PKM2
            drive their growth.”                                                                                               potential inhibitors using in   Glycolysis is initiated by
                                                                                                                               silico docking, could further   hexokinase (HK), which
            by Sundram Singh and Swati Sangolgi, Master's (Animal Biochemistry), ICAR-NDRI, Karnal
                                                                                                                               advance both detection and   phosphorylates glucose and
                                                                                                                               therapeutic strategies.   thereby traps it within the
                                               Abstract                           through HIF-1α–mediated cytokine
                                                                                                                               Emerging evidence on these   cell. In the context of
                                               Mastitis, one of the costliest diseases   production. At the same time,
                                                                                                                               enzymes in mastitis and   mastitis, HK functions as the
                                               in dairy herds, is increasingly    disruption of the tricarboxylic acid
                                                                                                                               sepsis highlights their   critical gateway enzyme that
                                               recognized not only as an infectious   (TCA) cycle leads to the accumulation
                                                                                                                               potential as targets for   secures a continuous energy
                                               disorder but also as a metabolic one.   of succinate—a pro-inflammatory
                                                                                                                               innovative diagnostic and   supply. Its expression and
                                               During infection, mammary and      metabolite—and itaconate, which
                                                                                                                               metabolic interventions,   activity are closely regulated
                                               immune cells undergo profound      exerts antibacterial and anti-
                                                                                                                               offering new opportunities   by signalling pathways such
                                               metabolic reprogramming that fuels   inflammatory effects.
                                                                                                                               for earlier disease detection,   as PI3K/Akt/mTOR, which are
                                               both defence and inflammation.     The pentose phosphate pathway (PPP)
                                                                                                                               reduced dependence on     activated by insulin and
                                               Glycolysis is rapidly upregulated,   is also redirected to produce NADPH,
                                                                                                                               antibiotics, and more     growth factors. This
                                               driven by key enzymes such as      sustaining reactive oxygen species
                                                                                                                               sustainable approaches to   regulation enhances HK
                                               hexokinase (HK), phosphofructokinase   (ROS) generation that contributes to
                                                                                                                               udder health management.  transcription and promotes
                                               (PFK), and pyruvate kinase (PK), which   pathogen clearance but also causes
                                                                                                                               Introduction              its association with
                                               amplify inflammatory signalling    tissue damage. These interconnected
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