Carboxylase

Tie JK et al (2016) Characterization of vitamin K-dependent carboxylase mutations that cause bleeding and nonbleeding disorders. Blood 127:1847-1855.

Enzymes that incorporate C02 as a carboxy group into a substrate. The process catalyzed by a carboxylase is called carboxylation. The process of carboxylation is ATP-dependent. Carboxylases have biotin as a prosthetic group.

The most important carboxylase is ribulose-1,5-bisphosphate carboxylase, an enzyme that binds carbon dioxide to ribulose-1,5-bisphosphate during photosynthesis (Calvin cycle
)This carboxylation introduces carbon dioxide from water or air into the metabolism of photosynthetic plants.

Other important carboxylases are:

• Acetyl-CoA-carboxylase, which converts acetyl-coenzyme A to malonyl-coenzyme A (fatty acid synthesis)
• Pyruvate carboxylase, which converts pyruvate (pyruvic acid) to oxalate (citrateklus)
• Glutamate carboxylase, which carboxylates glutamic acid to y-carboxyl-glutamic acid (vitamin K cycle)

Carboxylases play an important role in the synthesis of the coagulation factors Factor II, Factor VII, Factor IX, and Factor X as well as Protein S and Protein C. Vitamin K catalyzes the final step in the synthesis of these factors. Here, glutamic acid is carboxylated to y-carboxyl-glutamic acid under the action of a carboxylase, together with CO2 as substrate.

A lack of enzyme activity of pyruvate, propionyl-CoA and 3-methylcrotonyl-CoA carboxylase leads to complex disorders in the breakdown of carbohydrates and the amino acids leucine, isoleucine, valine, threonine and methionine (see below carboxylase defect multiple).

1. Narang MA et al (2004) Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase. Hum Mol Genet 13: 15-23
2. Sweetman L, Nyhan WL (1986) Inheritable biotin-treatable disorders and associated phenomena. Ann Rev Nutr 6: 317-343