carboxylasesoften

Carboxylases are enzymes that catalyze the carboxylation of substrates, meaning they introduce a carboxyl group (CO2 or bicarbonate) into organic molecules. They are essential in metabolism and, in photosynthetic organisms, in fixing inorganic carbon into organic matter. Carboxylases are diverse in their cofactors, reaction mechanisms, and biological roles.

Biotin-dependent carboxylases include pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase. These enzymes typically use ATP to activate CO2 and transfer it to a substrate via a biotin prosthetic group. They participate in replenishing the TCA cycle (pyruvate carboxylase), fatty acid synthesis (acetyl-CoA carboxylase via malonyl-CoA), and the degradation of certain amino acids and odd-chain fatty acids (propionyl-, methylcrotonyl-CoA carboxylases).

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is the best-known non-biotin carboxylase. Located in plants, algae, and many bacteria, it fixes atmospheric CO2 into ribulose-1,5-bisphosphate during photosynthesis, producing 3-phosphoglycerate. RuBisCO also catalyzes oxygenation reactions that compete with carboxylation, affecting photosynthetic efficiency.

Other carboxylases participate in metabolism and physiology across organisms, including bacterial CO2-fixation enzymes and various biosynthetic pathways that generate carboxylated sugars, acids, and amino acids. Clinically, defects in biotin-dependent carboxylases can cause metabolic disorders, and biotechnological efforts exploit carboxylases to produce value-added chemicals through metabolic engineering.