Page 12 - Think Grain Thin Feed Oct 2025

www.benisonmedia.com ARTICLE metabolic fuel. PFK, plays a special role. escalates or resolves.

Think Grain Think Feed - Volume 11 | Issue 12 | Oct 2025

Instead of only working in
The Pentose Phosphate
Phosphofructokinase (PFK)
the cytoplasm, PK can
Pathway: Fuelling ROS and
catalyzes the key
commitment step of
where it binds to hypoxia-
glycolysis. Increased PFK
The pentose phosphate
activity drives glucose translocate into the nucleus, Inflammation
inducible factor 1-alpha (HIF-
pathway (PPP), which
deeper into the pathway, 1α). This complex enhances branches off from glycolysis,
sustaining rapid energy transcription of pro- is also reprogrammed in
production. Under stress inflammatory cytokines, mastitis. In activated
conditions such as hypoxia particularly interleukin-1β macrophages, PPP activity
or oxidative stress, (IL-1β) (Krawczyk et al., 2010; increases, producing NADPH
upregulation of PFK activity Rodríguez-Prados et al., (Yu et al., 2019). NADPH
promotes a metabolic shift 2010; Liu et al., 2022). drives NADPH oxidases,
toward anaerobic glycolysis, The TCA Cycle Stalls and which generate reactive
ensuring continued ATP Makes Trouble oxygen species (ROS). While
production when Under normal conditions, ROS are essential for
mitochondrial oxidative pyruvate from glycolysis is bacterial killing, their
phosphorylation is impaired. fed into the TCA cycle, overproduction damages
This metabolic plasticity is producing a steady supply of mammary tissue and
particularly important in energy. But mastitis disrupts prolongs inflammation (Saito
rapidly dividing cells, this cycle, leading to et al., 2021; Ushio-Fukai et
including tumour cells and metabolic bottlenecks that al., 2021).
proliferating follicular cells. generate inflammatory Dysbiosis in the gut has
A central regulator of this metabolites. similarly been associated
step is PFKFB3, which Succinate accumulates when with PPP upregulation,
produces fructose-2,6- the cycle is impaired. linking gastrointestinal
bisphosphate, a potent Succinate acts as a pro- microbial imbalance to
allosteric activator of PFK. In inflammatory metabolite, mastitis at the immune-
mastitis, PFKFB3 expression stabilizing HIF-1α and metabolic interface (Horst et
in mammary cells is elevated, promoting sustained IL-1β al., 2021; Kheirandish et al.,
and its inhibition has been production (Tannahill et al., 2022).
shown to reduce reactive 2013; Mills & O'Neill, 2014). At the same time, the PPP
oxygen species generation, Itaconate is produced as an contributes to antioxidant
suppress HIF-1α signalling, alternative pathway product. defence. Sedoheptulose
and alleviate Staphylococcus Itaconate has direct kinase (Shpk), a unique
aureus-induced antibacterial effects against enzyme of this pathway,
inflammation, underscoring pathogens such as generates sedoheptulose-7-
its importance as both a Mycobacterium tuberculosis phosphate, which supports
metabolic driver and a and also reduces NADH production and
potential therapeutic target inflammation by activating enhances cellular antioxidant
(Gao et al., 2024), as shown the Nrf2 pathway and capacity (Haschemi et al.,
in Fig.1. Targeting glycolytic restraining type I interferon 2012; Nagy & Haschemi,
regulators has therefore responses (Michelucci et al., 2015). These findings
emerged as a promising 2013; Mills et al., 2018). Thus, emphasize the dual nature of
strategy to control this the TCA cycle doesn't just the PPP: depending on
metabolic overactivation. slow down in mastitis but context, it can exacerbate
Pyruvate kinase (PK), also actively shapes whether oxidative stress and
produced downstream of the immune response
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