An enzyme is a protein that serves as a biological catalyst, significantly speeding up specific chemical reactions within cells without being consumed in the process. Transketolase is one such enzyme, playing a role in how our cells process energy and building blocks. It is widely expressed across various tissues in the human body, including the liver, mammary glands, adrenal glands, and cornea.
Transketolase’s Metabolic Role
Transketolase plays a central role within the pentose phosphate pathway (PPP), a metabolic route distinct from the primary energy-generating pathways. This enzyme facilitates the transfer of two-carbon units between sugar molecules, connecting the PPP with glycolysis, the main carbohydrate metabolic pathway. Through this action, transketolase helps regulate the flow of carbon compounds, allowing cells to adjust to varying metabolic needs.
The PPP is not primarily designed to produce adenosine triphosphate (ATP), the cell’s main energy currency, but rather generates two other important products: NADPH and ribose-5-phosphate. NADPH is a molecule important for maintaining cellular health, particularly in antioxidant defense. It helps protect cells from damage caused by reactive oxygen species. Ribose-5-phosphate is another important output of the PPP, serving as a foundational building block for the synthesis of nucleotides. Nucleotides are the basic units that form DNA and RNA, which carry genetic information and are involved in protein synthesis. Therefore, transketolase’s activity in the PPP indirectly supports genetic integrity and cellular replication.
The Cofactor: Thiamine
Transketolase requires a specific “helper molecule” known as thiamine pyrophosphate (TPP) to function correctly. TPP is derived from dietary thiamine, commonly known as Vitamin B1. TPP binds to transketolase, enabling the enzyme to perform its carbon transfer reactions.
A deficiency in thiamine directly impacts transketolase activity, leading to impaired function of the pentose phosphate pathway. When transketolase cannot operate efficiently due to insufficient TPP, the body’s ability to produce NADPH and ribose-5-phosphate is compromised. Reduced NADPH levels can diminish antioxidant capacity, making cells more vulnerable to oxidative stress.
Severe thiamine deficiency can lead to serious health conditions, such as Wernicke-Korsakoff syndrome, which primarily affects the nervous system. The neurological symptoms observed in this syndrome are partly attributed to the impaired transketolase function in brain cells. The brain relies heavily on glucose metabolism and is particularly sensitive to disruptions in pathways like the PPP, which support its metabolic needs.
Transketolase and Human Health
Beyond its direct link to thiamine deficiency, altered transketolase activity or genetic variations in the enzyme are associated with other health conditions. For example, some types of cancer exhibit increased activity of the pentose phosphate pathway, a phenomenon linked to the Warburg effect. This elevated PPP activity, driven by transketolase, helps rapidly dividing cancer cells produce the necessary building blocks and NADPH for growth and survival.
The enzyme’s involvement in glucose metabolism also suggests a potential role in diabetes. Research is exploring how changes in transketolase activity might contribute to metabolic imbalances seen in diabetic conditions, though these interactions are complex.
Additionally, rare genetic disorders affecting the TKT gene, which codes for transketolase, have been identified. One such condition, transketolase deficiency (SDDHD), is an inherited recessive mutation causing developmental delays, short stature, and congenital heart defects. Its expression levels have been observed to increase during certain infections and in conditions like HIV-1 and sepsis, suggesting a broader involvement in the body’s response to stress and disease.