Thematic collection honors 55 years of PEPCK research
Over the past 55 years, many important studies on the enzymology, genetics and metabolic role of phosphoenolpyruvate carboxykinase (GTP) (also known as PEPCK) have graced the pages of the Journal of Biological Chemistry. Whether it’s the original trilogy of articles from 1954 by Merton F. Utter describing the purification and preliminary characterization of the mitochondrial form of PEPCK (then referred to as oxalacetic carboxylase) or Richard W. Hanson’s widely read 2007 article detailing the metabolic effects of overexpressing the cytosolic form of PEPCK in mouse skeletal muscle, JBC always has published cutting-edge research on the important enzyme.
Perhaps fittingly, then, the journal has decided to mark the 55th anniversary of the publication of Utter’s articles with a special PEPCK compendium that combines both research and review articles.
On the research side, the collection features the seminal article by Utter and Kiyoshi Kurahashi describing the purified enzyme, along with 10 other articles that have appeared in the JBC in the past decade.
The recent articles cover a variety of biological areas, including the regulation of PEPCK transcription by factors such as glucocorticoids, functional insights gained from recent structural analysis and the evolving story of the enzyme’s metabolic role in vertebrates.
The compendium also contains three minireview articles published in the JBC in October. The first, by Gerald M. Carlson and Todd Holyoak, provides insight into the reaction mechanism of PEPCK. Despite the efforts of many dedicated researchers, the mechanism of PEPCK has remained elusive over the years, but recent high-resolution structures of the enzyme from a variety of organisms have revealed details about the reaction’s reversibility and nucleotide specificity.
That new information has clarified the metabolic role of PEPCK, a topic covered in the second minireview by Jianqi Yang, Satish C. Kalhan and Hanson. Rather than being involved exclusively in gluconeogenesis as originally thought, PEPCK plays a broader role in cataplerosis, the process of removing anions from the citric acid cycle. Thus, PEPCK has a role in four metabolic pathways: gluconeogenesis, glyceroneogenesis, serine synthesis and the conversion of amino acid carbon skeletons to pyruvate for subsequent oxidation in the citric acid cycle.
The third minireview, by Jianqi Yang, Lea Reshef, Hanoch Cassuto, Gabriela Aleman and Hanson, discusses transcription control of the gene for the cytosolic form of PEPCK. The authors note the emerging importance of histone modification as a key regulator of tissue-specific PEPCK-C transcription and also highlight the insights that may be gained from a critical analysis of the PEPCK-C gene promoter across an evolutionary range of species.
Hanson, who in addition to contributing to the minireview series helped coordinate the JBC compendium, notes that, despite 55 years of research on the mechanisms, metabolism and molecular biology of PEPCK, many gaps in our knowledge still remain. However, he said he is confident that research on the fascinating enzyme shows no signs of slowing down, and he’s looking forward to celebrating many more PEPCK anniversaries in the future.
Nick Zagorski (firstname.lastname@example.org) is a science writer at ASBMB.