Thiamine transporter (THTR)

Thiamine transporters, primarily Thiamine transporter 1 (THTR-1/SLC19A2) and Thiamine transporter 2 (THTR-2/SLC19A3), are specialized membrane proteins that mediate the high-affinity uptake of thiamine (vitamin B1) into cells [1, 2]. Thiamine is a critical micronutrient required for the synthesis of thiamine pyrophosphate, an essential cofactor for key enzymes in glucose metabolism, such as the pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase [3]. THTR-1 is ubiquitously expressed and serves as the primary route for intestinal absorption and renal reabsorption, while THTR-2 is highly expressed in the brain and is vital for maintaining cerebral thiamine levels [2, 4]. Genetic mutations in SLC19A2 lead to Thiamine-responsive megaloblastic anemia (TRMA), whereas mutations in SLC19A3 cause Biotin-thiamine-responsive basal ganglia disease (BTBGD), both of which are severe metabolic disorders [5, 6]. These transporters are also significant in pharmacology as sites of drug-induced toxicity; for instance, the JAK2 inhibitor fedratinib was found to potently inhibit THTR-2, leading to cases of Wernicke’s encephalopathy in clinical trials [7]. Additionally, common drugs like metformin have been shown to interact with these transporters, potentially affecting thiamine homeostasis in diabetic patients [8]. Understanding the kinetics and expression patterns of these transporters is essential for managing nutritional deficiencies and predicting potential toxicities of new therapeutic agents [4, 7].

Other names

SLC19A2SLC19A3Solute carrier family 19 member 2Solute carrier family 19 member 3THTR-1THTR-2Thiamine transporter 1Thiamine transporter 2

Facilitated transport of thiamine across the plasma membrane into the cytoplasm; competitive inhibition of thiamine uptake by certain drugs.