Physiological Characterization of Arginine Kinase Found in Caenorhabditis elegans

Abstract

Phosphagen kinases (PKs) are a family of enzymes that catalyze the reversible transfer of the high‐energy phosphate group of ATP to a guanidino containing substrate molecule. PKs are involved in maintaining energy homeostasis in response to a sudden, high‐energy demand. There are eight classes of phosphagen kinases based on the substrate they bind. Of these, creatine kinase (CK), found in vertebrates, and arginine kinase (AK), found in invertebrates, are the most widely studied. It has been proposed that AK is the most ancestral PK, and that the others, including CK, have evolved from the AK enzyme. CKs have been well studied physiologically in mice and previous experiments in mice that lack CK isoforms found decreased stress tolerance, decreased muscle function, and increased amounts of mitochondrial volume. By comparison, less is known about the AKs and their role in cellular physiology. We are exploring the potential of using an invertebrate model system for the study of the physiological role of AKs. To facilitate this, we have worked with the C. elegans Genetics Consortium at the University of Oklahoma's Advanced Center for Genome Technology to construct knockouts of four of the AKs in C. elegans. Two of these, W10 and F44 were genetically backcrossed with wild type to isolate the deletion in a wild type background. Through comparison to a wild type strain, the impact that each missing AK isoform has on physiological characteristics, such as aging, energy availability, and burst activity of muscle, will be examined. By comparing two distantly related organisms, with similar PK systems, it is our goal to identify conserved physiological functions of the PK family of enzymes.