Role of the phosphocreatine system on energetic homeostasis in skeletal and cardiac muscles

Abstract

Adenosine triphosphate is the present energy currency in the body, and is used in various cellular and indispensable processes for the maintenance of cell homeostasis. The regeneration mechanisms of adenosine triphosphate, from the product of its hydrolysis – adenosine diphosphate – are therefore necessary. Phosphocreatine is known as its quickest form of regeneration, by means of the enzyme creatine kinase. Thus, the primary function of this system is to act as a temporal energy buffer. Nevertheless, over the years, several other functions were attributed to phosphocreatine. This occurs as various isoforms of creatine kinase isoforms have been identified with a distinct subcellular location and functionally coupled with the sites that generate and use energy, in the mitochondria and cytosol, respectively. The present study discussed the central and complex role that the phosphocreatine system performs in energy homeostasis in muscle cells, as well as its alterations in pathological conditions.

An impaired metabolism of nucleotides underpins a novel mechanism of cardiac remodeling leading to Huntington's disease related cardiomyopathy

“…It is also well established that the major source of ATP regeneration is the creatine kinase system [47]. Depletion of the phosphocreatine (PCr) concentration is a typical feature of heart failure and has been described in many different animal models of cardiomyopathy [48,49].…”

Unique Metabolic Adaptations Dictate Distal Organ-Specific Metastatic Colonization

“…Hepatic creatine production and export to other organs is an important system for ATP recycling and storage (da Silva et al, 2009). Creatine can hold a phosphate group as phosphocreatine, and acts as a phospho-donor to maintain a proper ADP:ATP ratio or replenish ATP in conditions of intense exercise or brain activity (Guimaraes-Ferreira, 2014). Liver metastases originating from colorectal tumors induce the secretion of creatine kinase, brain-type (CKB) into the microenvironment through downregulation of miR-483 and miR-551a (Loo et al, 2015).…”

Galanin receptors activation modulates myocardial metabolic and antioxidant responses to ischaemia/reperfusion stress

“…In addition, the administration of peptide G1 significantly increased myocardial PCr/Cr ratio and ΣCr content, thus reflecting, respectively, better integrity of cell membranes 10 and the functional coupling of the different isoforms of creatine kinase in the phosphocreatine "shuttle" system. 12 Improving myocardial energy state by the peptides was accompanied by a profound decrease in lactate accumulation in the AAR indirectly indicating a decrease in glycogenolysis. Energy metabolism is an important determinant of cell survival and maintaining the structure and function of cell organelles in the post-ischaemic heart.…”

“…3 The N-terminal part is a fragment of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) and the C-terminal part is the other bioactive dipeptide L-carnosine capable of scavenging hydroxyl radicals (Table 1). 6 A fragment of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) contains residues Trp, 2 Asn, 5 Gly 8 and Tyr, 9 which are necessary for interaction of the peptide with the GalR2 receptor 7,8 and thereby to trigger cardioprotective effects. L-carnosine tailing to C-terminal part of peptide G1 enhances its resistance to the action of exopeptidases due to the insertion of βAla14.…”

“…Post-ischaemic administration of the peptides improved functional recovery of isolated perfused rat hearts and reduced infarct size in rats in vivo. 4,5 The chimeric ligand [βAla14, His15]-galanin (2-15) (G1), which is composed of galanin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) and the dipeptide carnosine, exhibited the most beneficial effect. 3 The mechanisms of action of peptide G1 remain unclear.…”