karboksülaasi

Karboksülaasi (carboxylase) is an enzyme that catalyzes the addition of a carboxyl group to a substrate, typically using CO₂ and a cofactor such as biotin. The reaction is essential in several metabolic pathways, including the assimilation of inorganic carbon in autotrophic organisms and the synthesis of important biomolecules in animals. Carboxylases are classified as CO₂-dependent, water-dependent, or heterologously expressed enzymes based on their catalytic mechanisms and membrane associations.

The first carboxylase identified was ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), the key enzyme of photosynthetic carbon fixation in plants, algae, and cyanobacteria. Subsequent discoveries revealed a variety of carboxylase enzymes in animal tissues, such as pyruvate carboxylase, involved in gluconeogenesis, and anaplerotic reactions that replenish tricarboxylic acid cycle intermediates. In bacteria, carboxylases participate in the biosynthesis of essential amino acids, fatty acids, and the activation of fatty acids to acyl-CoA derivatives.

Carboxylases generally require biotin as a prosthetic group; the biotin moiety is covalently attached to a lysine residue on the enzyme and undergoes cyclic transfer of a carboxyl group. This mechanism is facilitated by ATP and involves the formation of a carboxyphosphate intermediate. In addition to biotin-dependent enzymes, formate dehydrogenase and other metal-dependent carboxylases use Zn²⁺ or Fe²⁺ to coordinate CO₂ activation.

Therapeutic interventions targeting carboxylases are under investigation for metabolic disorders like congenital hyperinsulinism, where inhibition of pyruvate carboxylase could reduce insulin secretion. Moreover, engineered carboxylases are explored in synthetic biology for CO₂ capture and conversion in industrial bioprocesses.