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From: The wide phenotypic spectrum of thiamine metabolism dysfunction syndrome 5 and its treatment
Thiamine pathways: (A) Thiamine undergoes phosphorylation to produce thiamine pyrophosphate (TPP) through the action of thiamine pyrophosphokinase 1 (hTPK1). Further phosphorylation by mitochondrial thiamine triphosphosphate synthase results in thiamine triphosphate (TTP). Thiamine can be dephosphorylated to thiamine monophosphate (TMP) and thiamine by thiamine phosphatase. (B) The absorption of thiamine in the small intestine and its entry into cells involve transporters encoded by SLC19A2/SLC19A3. Inside cells, thiamine is pyrophosphorylated to its active form (TPP) by hTPK1. TPP serves as a cofactor for three dehydrogenases in mitochondria: (1) pyruvate dehydrogenase complex (PDHC), (2) branched-chain alfa-keto acid dehydrogenase (BCKDH), and (3) alpha-ketoglutarate dehydrogenase (α-KGDH). Outside of mitochondria, TPP functions as a cofactor for Transketolase and 2-hydroxyacyl-CoA Lyase 1 (HACL1)