3-Hydroxybutyryl-CoA dehydrogenase

3-Hydroxybutyryl-CoA dehydrogenase is an enzyme that plays a crucial role in the metabolic process known as beta-oxidation, in which fatty acids are broken down to generate acetyl-CoA, a key molecule in energy production. This enzyme specifically catalyzes the third step of beta-oxidation, the conversion of 3-hydroxybutyryl-CoA to acetoacetyl-CoA, while simultaneously reducing NAD+ to NADH. This reaction is vital for the metabolism of fatty acids, particularly during periods of fasting or low-carbohydrate intake, when fatty acids become a primary energy source.

Function[edit | edit source]

The primary function of 3-Hydroxybutyryl-CoA dehydrogenase is to facilitate the conversion of 3-hydroxybutyryl-CoA, a molecule generated during the second step of beta-oxidation, into acetoacetyl-CoA. This reaction is essential for the continued breakdown of fatty acids, allowing for the release of acetyl-CoA, which can then enter the citric acid cycle (also known as the Krebs cycle) to produce energy. Additionally, the reaction produces NADH, which is a crucial cofactor in the electron transport chain, further contributing to energy production within the cell.

Structure[edit | edit source]

3-Hydroxybutyryl-CoA dehydrogenase is a protein that is encoded by the HBDH gene in humans. The enzyme is located in the mitochondria, where beta-oxidation primarily occurs. Its structure allows it to bind to its substrate, 3-hydroxybutyryl-CoA, and catalyze its conversion to acetoacetyl-CoA efficiently.

Clinical Significance[edit | edit source]

Mutations in the gene encoding 3-Hydroxybutyryl-CoA dehydrogenase can lead to metabolic disorders, including 3-Hydroxyacyl-CoA Dehydrogenase Deficiency, a rare condition that affects the body's ability to break down certain fatty acids. This can result in symptoms such as hypoglycemia, muscle weakness, and cardiomyopathy. Early diagnosis and dietary management are crucial for managing this condition.