The phosphorylation of thiamine (B1) occurs by two main enzymes: thiamine diphosphokinase, which catalyzes the formation of thiamine pyrophosphate (TPP) using ATP,
The protein encoded by this gene functions as a homodimer and catalyzes the conversion of thiamine (B1) to thiamine pyrophosphate (ThDP) , a cofactor for some enzymes of the glycolytic and energy production pathways. Defects in this gene are a cause of thiamine metabolism dysfunction syndrome-5. [provided by RefSeq, Apr 2017]
GeneCards Summary for TPK1 Gene
TPK1 (Thiamin Pyrophosphokinase 1) is a Protein Coding gene. Diseases associated with TPK1 include Thiamine Metabolism Dysfunction Syndrome 5 and Childhood Encephalopathy Due To Thiamine Pyrophosphokinase Deficiency. Among its related pathways are Metabolism of water-soluble vitamins and cofactors and Metabolism. Gene Ontology (GO) annotations related to this gene include kinase activity and thiamine binding.
LÄHDE: Martin A. Crook, in Laboratory Assessment of Vitamin Status, 2019
Thiamine TPP is produced by thiamine diphosphokinase and is an essential cofactor for the decarboxylation of 2-oxoacids, such as the conversion of pyruvate to acetyl coenzyme a and also other pathways including pyruvate dehydrogenase (PDH), α-ketogluterate dehydrogenase (KGDH), and branched-chain α-keto acid dehydrogenase (BCKDH), (Fig. 6.2). In thiamine deficiency, pyruvate cannot be metabolized and accumulates in the blood. Thiamine TPP is also an essential cofactor for transketolase in the pentose-phosphate pathway
Thiamine is essential for the optimal function of the nervous system and repair of myelin nerve sheaths. In turn magnesium is an important cofactor for thiamine-dependent enzymes.2–9 In addition, other reputed noncofactor roles of thiamine compounds are shown within the oxidative stress response, gene regulation, cholinergic system, immune function, chloride channels, and neurotransmission.2–6
LÄHDE: Barbara Plecko, Robert Steinfeld, in Swaiman's Pediatric Neurology (Sixth Edition), 2017
Thiamine Pyrophosphokinase Deficiency
Autosomal-recessive thiamine pyrophosphokinase deficiency (OMIM 606370) presents with a late-onset Leigh-like disease and basal ganglia changes on MRI. During acute episodes, elevated blood and CSF lactate and enhanced excretion of α-ketoglutarate are consistent findings. Thiamine pyrophosphate (TPP) concentrations in blood and muscle are reduced, and diagnosis is confirmed by sequencing of the TPK1 gene. Thiamine supplementation at 100- to 200 mg/day was of limited benefit in symptomatic patients. Earlier intervention with doses around 500 mg/day may be associated with better prognosis.
- TPK1 , Thiamin pyrophosphokinase 1 , (7q35)
Orphanet: 58 Childhood encephalopathy due to thiamine pyrophosphokinase (TPK1) deficiency is a rare inborn error of metabolism disorder characterized by early-onset, acute, encephalopathic episodes (frequently triggered by viral infections), associated with lactic acidosis and alpha-ketoglutaric aciduria, which typically manifest with variable degrees of ataxia, generalized developmental regression (which deteriorates with each episode) and dystonia. Other manifestations include spasticity, seizures, truncal hypotonia, limb hypertonia, brisk tendon reflexes and reversible coma.
MalaCards based summary: Childhood Encephalopathy Due to Thiamine Pyrophosphokinase Deficiency and has symptoms including ataxia and muscle spasticity. An important gene associated with Childhood Encephalopathy Due to Thiamine Pyrophosphokinase Deficiency is TPK1 (Thiamin Pyrophosphokinase 1). Affiliated tissues include whole blood and brain.
Thiamine triphosphate: a ubiquitous molecule in search of a physiological role
Thiamine triphosphate (ThTP) was discovered over 60 years ago and it was long thought to be a specifically neuroactive compound. Its presence in most cell types, from bacteria to mammals, would suggest a more general role but this remains undefined. In contrast to thiamine diphosphate (ThDP), ThTP is not a coenzyme. In E. coli cells, ThTP is transiently produced in response to amino acid starvation, while in mammalian cells, it is constitutively produced at a low rate. Though it was long thought that ThTP was synthesized by a ThDP:ATP phosphotransferase, more recent studies indicate that it can be synthesized by two different enzymes: (1) adenylate kinase 1 in the cytosol and (2) FoF1-ATP synthase in brain mitochondria. Both mechanisms are conserved from bacteria to mammals. Thus ThTP synthesis does not seem to require a specific enzyme. In contrast, its hydrolysis is catalyzed, at least in mammalian tissues, by a very specific cytosolic thiamine triphosphatase (ThTPase), controlling the steady-state cellular concentration of ThTP. In some tissues where adenylate kinase activity is high and ThTPase is absent, ThTP accumulates, reaching ≥ 70% of total thiamine, with no obvious physiological consequences. In some animal tissues, ThTP was able to phosphorylate proteins, and activate a high-conductance anion channel in vitro. These observations raise the possibility that ThTP is part of a still uncharacterized cellular signaling pathway. On the other hand, its synthesis by a chemiosmotic mechanism in mitochondria and respiring bacteria might suggest a role in cellular energetics.