Interaction of creatine kinase and adenylate kinase systems in muscle cells

Abstract

Elsewhere in this book the important role of creatine kinase and its metabolites in high energy phosphate metabolism and transport in muscle cells has been reviewed. The emphasis of this review article is mainly on the compartmentalized catalytic activity of adenylate kinase in relation to creatine kinase isoenzymes, and other enzymes of energy production and utilization processes in muscle cells. At present the role of adenylate kinase is considered simply to equilibrate the stores of adenine nucleotides. Recent studies by us and others, however, suggest an entirely new view of the metabolic importance of adenylate kinase in muscle function. This view offers a closer interaction between adenylate kinase and creatine kinase, in the process of energy production (at mitochondrial and glycolytic sites), and energy utilization (at myofibrillar sites and perhaps other sites such as sarcoplasmic reticular, sarcolemmal membrane, etc.), thus being an integral part of the high energy phosphate transport system. This review article opens up the opportunity to further examine the metabolism of adenine nucleotides and their fluxes through the adenylate kinase system in intact muscle cells. Using an intact system, having a preserved integrity of their compartmentalized enzymes and substrates, is essential in clarifying the exact role of adenylate kinase in high energy phosphate metabolism in muscle cells.

ADP delivery from adenylate kinase in the mitochondrial intermembrane space to oxidative phosphorylation increases in the presence of macromolecules

“…Data presented in this paper lend support to the hypothesis of an AK shuttle [10,21,28]. In tissues with high activities of mitochondrial and cytoplasmic AK, like liver, these enzymes can contribute to the ADP transport into the mitochondria at least under conditions of elevated cytoplasmic AMP concentrations.…”

Use of gene targeting for compromising energy homeostasis in neuro-muscular tissues: The role of sarcomeric mitochondrial creatine kinase

“…The AKmit mediated stimulus of oxidative phos phorylation is comparable to, or even higher than, the CKmit mediated increase (Gellerich, 1992;Gellerich et al, 1994). It is therefore tempting to speculate that both shuttles contribute to the A T P /A D P conversions at the mitochondrial site (Savabi, 1994). Bessmann and Carpen ter (1985) suggested the existence of a tetrahedral arrange ment of one molecule of CKmit with two molecules of AKmit clustered around the ANT.…”

Adenylate Kinase 1 Deficiency Induces Molecular and Structural Adaptations to Support Muscle Energy Metabolism

“…Together, the increased steady-state levels for several glycolytic mRNA species and the more direct observation of increased enzymatic activity of PK and PGK, indicate that glycolysis-driven phosphoryl exchange between ADP and ATP may be one of the principal targets for adaptation in fast-twitch muscles of AK1 Ϫ/Ϫ mice. AK1-deficient Muscle Show Increased Mitochondrial Content-Based on theoretical considerations and experimental evidence it is now commonly accepted that the AK, CK, and glycolytic circuits may be intertwined with mitochondrial activity and together form integrated networks for high energy phosphoryl transfer at different subcellular locales (13,16,23,32). As shown in Fig.…”

“…nl/celbio/data.htm for detailed information) onto Hybond N ϩ membranes using a gridding robot (24). 32 P-labeled single-stranded cDNA was used as probe to hybridize membranes with gridded cDNA arrays as previously described in detail elsewhere (24). Four AK1 knockout and control mice were analyzed and statistically compared.…”