Inhibitors of COMT are clinically used for the treatment Parkinson’s disease. Here, we report first natural pentacyclic triterpenoid-type inhibitors and their structure-activity relationships inhibition mechanism. The most potent compounds were found to be oleanic acid, betulinic acid celastrol with IC50 values 3.89–5.07 μM, that acted as mixed (uncompetitive plus non-competitive) COMT, represe...

Catechol-O-methyltransferase (COMT) is a magnesium-dependent, catecholamine-metabolizing enzyme, whose impaired activity has been positively associated with cardiovascular diseases, particularly hypertension. Consumption of some natural mineral-rich waters has been shown to exert protective effects on cardiovascular risk factors, eg. by decreasing arterial blood pressure and blood lipids. Howev...

Reward processing depends on dopaminergic neurotransmission and is modulated by factors affecting dopamine (DA) reuptake and degradation. We used fMRI and a guessing task sensitive to reward-related activation in the prefrontal cortex and ventral striatum to study how individual variation in genes contributing to DA reuptake [DA transporter (DAT)] and degradation [catechol-o-methyltransferase (...

BACKGROUND A putative interaction between cannabis and variation at rs4680 within the catechol-methyl-transferase (COMT) gene on psychosis has been reported, but not adequately replicated. AIMS To examine whether the relative risk of developing psychosis following use of cannabis is dependent upon variation within COMT. METHOD A longitudinal study of 2630 individuals from the Avon Longitudi...

BACKGROUND Personality traits such as novelty seeking (NS) are associated with substance dependence but the mechanism underlying this association remains uncertain. Previous studies have focused on the role of the dopamine pathway. OBJECTIVE Examine the relationships between allelic variants of the catechol-O-methyltransferase (COMT) gene, NS personality traits, and age of onset of drug use i...

Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are important estrogen-metabolizing enzymes that may affect breast cancer risk. Few studies have directly measured the expression of CYP1B1 and COMT genes in breast tissue samples. The subjects in this study were a subgroup of participants of the Shanghai Breast Cancer Study including 64 patients diagnosed with breast cancer a...

Twin studies have indicated a common genetic origin for intelligence and for variations in brain morphology. Our previous diffusion tensor imaging studies found an association between intelligence and white matter integrity of specific brain regions or tracts. However, specific genetic determinants of the white matter integrity of these brain regions and tracts are still unclear. In this study,...

Preeclampsia (PE) and fetal growth restriction (FGR) are serious complications of pregnancy, associated with greatly increased risk of maternal and perinatal morbidity and mortality. These complications are difficult to diagnose and no curative treatments are available. We hypothesized that the metabolomic signature of two models of disease, catechol-O-methyl transferase (COMT(-/-)) and endothe...

INTRODUCTION Smoking behaviors, including heaviness of smoking and smoking cessation, are known to be under a degree of genetic influence. The enzyme catechol O-methyltransferase (COMT) is of relevance in studies of smoking behavior and smoking cessation due to its presence in dopaminergic brain regions. While the COMT gene is therefore one of the more promising candidate genes for smoking beha...

INTRODUCTION Preterm birth is associated with a range of neurodevelopmental deficits, including corpus callosum (CC) abnormalities, which persist into late adolescence and early adulthood. A common single-nucleotide polymorphism in the catechol-o-methyl transferase (COMT) gene (Val158Met) is associated with cognition and brain structure and may play a role in neurodevelopment. It is not known w...