ABSTRACT
All five of the mammalian carboxylases catalyze the incorporation of bicarbonate as a carboxyl group into a substrate and employ a similar catalytic mechanism. In the carboxylase reaction, the carboxyl moiety is first attached to biotin at the ureido nitrogen opposite the side chain. Then the carboxyl group is transferred to the substrate. The reaction is driven by the hydrolysis of ATP to ADP and inorganic phosphate. Subsequent reactions in the pathways of the five mammalian carboxylases release CO2 from the product of the enzymatic reaction. Thus, these reaction sequences rearrange the substrates into more useful intermediates but do not violate the classic observation that mammalian metabolism does not result in the net fixation of carbon dioxide.[4]
The five carboxylases are pyruvate carboxylase (EC 6.4.1.1), methylcrotonyl-CoA carboxylase (EC 6.4.1.4), propionyl-CoA carboxylase (EC 6.4.1.3), and two isoforms of acetyl-CoA carboxylase (EC 6.4.1.2), denoted I and II, which are also known as a ACC and
b ACC. Each carboxylase catalyzes an essential step in intermediary metabolism (Fig. 2).
