Sorbitol-6-phosphate dehydrogenase (S6PDH)

Sorbitol-6-phosphate dehydrogenase (S6PDH) is an enzyme that catalyzes the reversible, NAD+-dependent conversion of D-sorbitol 6-phosphate to D-fructose 6-phosphate. This enzyme is primarily found in bacteria and plants, playing a central role in the metabolism of sugar alcohols and the phosphotransferase system (PTS). In pathogenic bacteria such as Streptococcus mutans, S6PDH is essential for the fermentation of sorbitol, a process that leads to the production of lactic acid and the subsequent development of dental caries (PubMed: 3891151). In plants, particularly those in the Rosaceae family like apples and pears, S6PDH is the key regulatory enzyme for sorbitol biosynthesis, which is vital for carbon transport and osmotic stress response (PubMed: 8643590). While humans do not possess a direct ortholog of S6PDH, the enzyme is a target for antimicrobial research aimed at disrupting bacterial energy pathways without affecting human glucose metabolism. The structural similarity of S6PDH to other members of the short-chain dehydrogenase/reductase (SDR) family presents a challenge for drug design, requiring high selectivity to avoid off-target effects (UniProt: P14229). Current research explores S6PDH inhibitors as potential non-fluoride agents for oral health maintenance.

Other names

D-sorbitol-6-phosphate dehydrogenaseKetose-6-phosphate reductaseS6P dehydrogenaseSorbitol-6-P dehydrogenase

Inhibition of bacterial sugar metabolism and energy production by blocking the conversion of sorbitol-6-phosphate to fructose-6-phosphate.