Document Type

Article

Publication Date

2-2025

Publisher

Elsevier

Source Publication

Archives of Biochemistry and Biophysics

Source ISSN

0003-9861

Original Item ID

DOI: 10.1016/j.abb.2024.110280

Abstract

Pyruvate carboxylase (PC) catalyzes the carboxylation of pyruvate to oxaloacetate which serves as an important anaplerotic reaction to replenish citric acid cycle intermediates. In most organisms, the PC-catalyzed reaction is allosterically activated by acetyl-coenzyme A. It has previously been reported that vertebrate PC can catalyze the hydrolysis of acetyl-CoA, offering a potential means for the enzyme to attenuate its allosteric activation. However, in the years since this initial report, there has been no further investigation of this phenomenon. The allosteric binding site for acetyl-CoA is now well characterized, enabling more detailed studies on acetyl-CoA hydrolysis at the allosteric site. Here, we confirm that slow acetyl-CoA hydrolysis is catalyzed by a bacterial PC from Staphylococcus aureus, indicating that this phenomenon is a broad feature of PC enzymes spanning the domains of life. Surprisingly, the enzyme can hydrolyze acetyl-CoA even when the binding site for the acetyl moiety is eliminated through truncation of the biotin carboxylase domain. This suggests that an alternative site for acetyl-CoA binding and hydrolysis may be present in the carboxyltransferase domain of S. aureus PC. We conclude that PC has evolved to minimize the rate of acetyl-CoA hydrolysis at the allosteric site and update the description of PC-catalyzed acetyl-CoA hydrolysis to suggest that this reaction is unlikely to play a significant physiological, metabolic or catalytic role.

Comments

Accepted version. Archives of Biochemistry and Biophysics, Vol. 764 (February 2025). DOI. © Elsevier Inc. Used with permission.

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