Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis.

Background: Thiamine diphosphate (ThDP), an indispensable cofactor for oxidative energy metabolism, is synthesized through the reaction thiamine + ATP ⇆ ThDP + AMP, catalyzed by thiamine pyrophosphokinase 1 (TPK1), a cytosolic dimeric enzyme. It was claimed that the equilibrium of the reaction is in favor of the formation of thiamine and ATP, at odds with thermodynamic calculations. Here we show that this discrepancy is due to feedback inhibition by the product ThDP.

Haploinsufficiency of the Attention-Deficit/Hyperactivity Disorder Risk Gene in Mice Causes Alterations in Cognition and Expression of Genes Involved in Myelination and Sialylation.

Genome wide association meta-analysis identified , a gene encoding the beta-galactosidase-alpha-2,3-sialyltransferase-III, as a risk gene for attention-deficit/hyperactivity disorder (ADHD). Although loss-of-function mutations in are implicated in non-syndromic autosomal recessive intellectual disability (NSARID) and West syndrome, the impact of haploinsufficiency on brain function and the pathophysiology of neurodevelopmental disorders (NDDs), such as ADHD, is unknown. Since null mutant mice display severe developmental delay and neurological deficits, we investigated the effects of partial inactivation of in heterozygous (HET) knockout ( ) mice on behavior as well as expression of markers linked to myelination processes and sialylation pathways.

Dibenzoylthiamine Has Powerful Antioxidant and Anti-Inflammatory Properties in Cultured Cells and in Mouse Models of Stress and Neurodegeneration.

Thiamine precursors, the most studied being benfotiamine (BFT), have protective effects in mouse models of neurodegenerative diseases. BFT decreased oxidative stress and inflammation, two major characteristics of neurodegenerative diseases, in a neuroblastoma cell line (Neuro2a) and an immortalized brain microglial cell line (BV2). Here, we tested the potential antioxidant and anti-inflammatory effects of the hitherto unexplored derivative O,S-dibenzoylthiamine (DBT) in these two cell lines.