UDP-glucose pyrophosphorylase (UGPase) (UGPase)

UDP-glucose pyrophosphorylase (UGPase), primarily represented by the UGP2 isoform in humans, is a fundamental metabolic enzyme that catalyzes the reversible conversion of glucose-1-phosphate and UTP into UDP-glucose and pyrophosphate (Creative Enzymes, 2024; NIH Gene, 2026). UDP-glucose is a critical activated sugar donor required for the biosynthesis of glycogen, glycoproteins, glycolipids, and proteoglycans, positioning UGPase as a central regulator of carbohydrate metabolism and protein glycosylation (NIH PMC, 2020; Wikipedia, 2024). In oncology, UGP2 is frequently overexpressed in cancers such as pancreatic ductal adenocarcinoma and hepatocellular carcinoma, where it promotes tumor progression by maintaining glycogen reserves and ensuring the proper glycosylation of oncogenic signaling proteins like EGFR (NIH PMC, 2021; ACS, 2025). Conversely, biallelic loss-of-function mutations in the UGP2 gene are the primary cause of Barakat-Perenthaler syndrome, a severe neurodevelopmental disorder characterized by early-onset epileptic encephalopathy (Wikipedia, 2024; NIH Gene, 2026). The enzyme is also a significant target in infectious diseases; because prokaryotic UGPases (often called GalU) are evolutionarily distinct from eukaryotic versions, they offer a pathway for developing selective antibiotics against pathogens like Streptococcus pneumoniae (NIH PMC, 2014; Semantics Scholar, 2005). Therapeutic strategies currently focus on small-molecule inhibitors such as GAL-012 and natural products like theaflavin to disrupt the metabolic dependencies of cancer cells (NIH PMC, 2020; ACS, 2025).

Other names

UTP--glucose-1-phosphate uridylyltransferaseGlucose-1-phosphate uridylyltransferaseUDPG pyrophosphorylaseUDP-glucose diphosphorylaseUGP2GalUUridyl diphosphate glucose pyrophosphorylase

Competitive or uncompetitive inhibition of the enzyme's catalytic activity to prevent the conversion of glucose-1-phosphate and UTP into UDP-glucose, thereby disrupting downstream glycogen storage and protein glycosylation pathways.