Transketolase

Transketolase is an essential enzyme involved in the pentose phosphate pathway (PPP), a metabolic pathway that plays a crucial role in the production of ribose-5-phosphate and NADPH. This enzyme catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, resulting in the formation of a new ketose and aldose.

Function

Transketolase is responsible for the interconversion of sugars with different carbon lengths. It transfers a two-carbon fragment from a ketose sugar, such as fructose-6-phosphate, to an aldose sugar, such as glyceraldehyde-3-phosphate. This reaction is important for the synthesis of ribose-5-phosphate, a key component in the production of nucleotides and nucleic acids.

Role in the Pentose Phosphate Pathway

The pentose phosphate pathway is a metabolic pathway that occurs in the cytoplasm of cells. It serves two main functions: the generation of NADPH, which is required for biosynthetic reactions and antioxidant defense, and the production of ribose-5-phosphate, a precursor for nucleotide synthesis.

Transketolase plays a crucial role in the non-oxidative phase of the pentose phosphate pathway. In this phase, it catalyzes the transfer of carbon units between different sugars, allowing for the rearrangement and interconversion of sugars with different carbon lengths. This process is essential for the production of ribose-5-phosphate, which is needed for the synthesis of nucleotides and nucleic acids.

Regulation

Transketolase activity is regulated by several factors, including the availability of substrates and the presence of cofactors. Thiamine pyrophosphate (TPP) is a cofactor required for the proper functioning of transketolase. It binds to the enzyme and facilitates the transfer of the ketol group between sugars.

Clinical Significance

Deficiencies in transketolase activity have been associated with several diseases, including Wernicke-Korsakoff syndrome and genetic disorders such as transketolase deficiency. Wernicke-Korsakoff syndrome is caused by a thiamine deficiency, which impairs the activity of transketolase and other thiamine-dependent enzymes. Transketolase deficiency, on the other hand, is a rare genetic disorder characterized by a deficiency in transketolase activity, leading to neurological symptoms and developmental abnormalities.