TPK1 Human

The TPK1 gene is located on chromosome 7 (7q35) in humans . The protein encoded by this gene functions as a homodimer, meaning it forms a complex with another identical protein molecule to become functional . The enzyme’s primary function is to catalyze the phosphorylation of thiamine to thiamine pyrophosphate .

Thiamine pyrophosphate (TPP) is a vital cofactor for enzymes such as pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase. These enzymes are integral to the glycolytic pathway and the citric acid cycle, which are critical for cellular energy production . By converting thiamine to TPP, TPK1 ensures the availability of this cofactor for these essential metabolic processes .

Mutations in the TPK1 gene can lead to a rare disorder known as Thiamine Metabolism Dysfunction Syndrome 5 (THMD5) . This condition is characterized by episodic encephalopathy, a neurological disorder that can cause recurrent episodes of brain dysfunction . Patients with THMD5 may experience symptoms such as confusion, ataxia, and seizures, which can be triggered by factors like infections or fasting .

Human recombinant TPK1 is produced using recombinant DNA technology, which involves inserting the human TPK1 gene into a suitable expression system, such as bacteria or yeast, to produce the enzyme in large quantities. This recombinant enzyme is used in research to study its structure, function, and role in thiamine metabolism. It can also be used in diagnostic assays to measure thiamine pyrophosphate levels in biological samples .

Research on TPK1 has provided insights into the molecular mechanisms of thiamine metabolism and its impact on human health. Studies have shown that reduced thiamine binding due to TPK1 mutations is a novel mechanism for TPK deficiency . Understanding these mechanisms can help develop therapeutic strategies for conditions related to thiamine metabolism dysfunction.