S4hydroxyglutarate

S4-hydroxyglutarate (S4HG) is an organic compound classified as a hydroxyglutarate, a derivative of glutaric acid with a hydroxyl group attached to the fourth carbon. It is a stereoisomer of 4-hydroxyglutarate, differing in the spatial arrangement of its atoms. The "S" designation indicates its specific configuration, following the Cahn–Ingold–Prelog priority rules, which categorizes chiral molecules based on their three-dimensional structure.

S4-hydroxyglutarate is primarily studied in the context of metabolic disorders and neurological research. It is a metabolite produced through the oxidation of lysine and hydroxylysine, amino acids involved in collagen synthesis. Elevated levels of 4-hydroxyglutarate isomers, including S4HG, have been linked to certain genetic conditions such as 4-hydroxybutyrate dehydrogenase deficiency and 4-hydroxyglutaric aciduria type I, a rare metabolic disorder caused by mutations in the *HGD* gene. This disorder can lead to neurological symptoms, including developmental delays, movement disorders, and seizures.

In biochemical research, S4-hydroxyglutarate is often examined for its role in cellular signaling and its potential impact on mitochondrial function. Some studies suggest that altered levels of hydroxyglutarates may contribute to oxidative stress and mitochondrial dysfunction, which are implicated in neurodegenerative diseases. Additionally, S4HG has been explored as a biomarker for monitoring disease progression or treatment response in metabolic and neurological disorders.

S4-hydroxyglutarate is typically analyzed using mass spectrometry techniques, such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS), due to its low abundance in biological samples. Synthetic S4-hydroxyglutarate is occasionally used in laboratory settings to investigate its biochemical effects or as a reference standard for analytical validation. Further research is ongoing to elucidate its precise physiological roles and potential therapeutic implications.