Tropinone reductase II

Tropinone reductase II (TRII) is an enzyme that plays a crucial role in the biosynthesis of tropane alkaloids, which are a class of alkaloids found in a variety of plant species. These alkaloids have significant pharmacological properties, including anticholinergic, stimulant, and anesthetic effects. TRII specifically catalyzes the reduction of tropinone to pseudotropine, a key step in the metabolic pathway leading to the production of various tropane alkaloids.

Function

TRII is involved in the biosynthetic pathway of tropane alkaloids, which are primarily synthesized in the roots of plants such as those belonging to the Solanaceae family, including Atropa belladonna (deadly nightshade), Coca (from which cocaine is derived), and Datura stramonium (jimsonweed). The enzyme catalyzes the stereospecific reduction of tropinone to pseudotropine, differing from Tropinone reductase I (TRI) which reduces tropinone to tropine. This reaction is critical as it dictates the type of alkaloids that will be produced downstream in the pathway.

Structure

The structure of TRII has been elucidated through various biochemical and crystallographic studies. It is a monomeric enzyme that requires NADPH as a cofactor for its reductive activity. The active site of TRII is specifically tailored to recognize and bind tropinone, facilitating its reduction to pseudotropine. The enzyme's structure is crucial for its specificity and catalytic efficiency.

Biological Significance

The production of tropane alkaloids is of considerable interest due to their wide range of pharmacological applications. Alkaloids such as scopolamine, hyoscyamine, and cocaine are used in medicine for their anticholinergic, analgesic, and anesthetic properties. The role of TRII in the biosynthesis of these compounds makes it a potential target for genetic and biochemical manipulation aimed at enhancing the production of specific alkaloids for pharmaceutical use.

Genetic Engineering

Advances in genetic engineering have allowed for the manipulation of the genes encoding TRII in various plant species. By overexpressing or silencing the TRII gene, researchers can influence the production of specific tropane alkaloids. This has implications for the pharmaceutical industry, where there is a demand for the large-scale production of these compounds.

Clinical Implications

Understanding the function and structure of TRII can also have clinical implications. For example, inhibitors of TRII could potentially be used to decrease the production of harmful alkaloids in plants, reducing the risk of poisoning from plants containing toxic tropane alkaloids. Conversely, enhancing TRII activity could increase the production of beneficial alkaloids used in medicine.

See Also

• Alkaloid
• Enzyme
• Genetic engineering
• Pharmacology
• Solanaceae