Phosphopantetheine adenylyltransferase (PPAT) (PPAT)

Phosphopantetheine adenylyltransferase (PPAT) is a critical enzyme in the Coenzyme A (CoA) biosynthetic pathway, catalyzing the penultimate step where 4'-phosphopantetheine is converted into dephospho-CoA. In humans, this enzymatic activity is contained within the bifunctional protein Coenzyme A synthase (COASY). While traditionally studied as a target for novel antibacterial agents due to its essentiality in microbes, recent research has identified human PPAT as a metabolic vulnerability in certain cancers, such as cervical carcinoma [2, 7]. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been shown in recent studies to exert off-target inhibitory effects on PPAT [7, 9]. When combined with metformin, empagliflozin-mediated inhibition of PPAT disrupts the intracellular Acyl-CoA/CoA ratio, triggering a 'metabolic crisis' that suppresses tumor cell growth and induces apoptosis [7]. This interaction represents a novel mechanism for drug repurposing in oncology, extending the utility of empagliflozin beyond its established roles in diabetes and heart failure.

Other names

4'-phosphopantetheine adenylyltransferaseDephospho-CoA pyrophosphorylaseCoenzyme A synthase (adenylyltransferase domain)CoaDPhosphopantetheine Adenylyl Transferase

Inhibition of the adenylyltransferase activity of Coenzyme A synthase, leading to a disruption of the intracellular Acyl-CoA/CoA ratio and subsequent metabolic stress in malignant cells.