Creatine kinase in ischemic and inflammatory disorders.

David Kitzenberg,Sean P Colgan,Louise E Glover

doi:10.1186/s40169-016-0114-5

David Kitzenberg, Sean P Colgan + Show 1 more

Open Access

https://doi.org/10.1186/s40169-016-0114-5

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Abstract

The creatine/phosphocreatine pathway plays a conserved and central role in energy metabolism. Compartmentalization of specific creatine kinase enzymes permits buffering of local high energy phosphates in a thermodynamically favorable manner, enabling both rapid energy storage and energy transfer within the cell. Augmentation of this metabolic pathway by nutritional creatine supplementation has been shown to elicit beneficial effects in a number of diverse pathologies, particularly those that incur tissue ischemia, hypoxia or oxidative stress. In these settings, creatine and phosphocreatine prevent depletion of intracellular ATP and internal acidification, enhance post-ischemic recovery of protein synthesis and promote free radical scavenging and stabilization of cellular membranes. The creatine kinase energy system is itself further regulated by hypoxic signaling, highlighting the existence of endogenous mechanisms in mammals that can enhance creatine metabolism during oxygen deprivation to promote tissue resolution and homeostasis. Here, we review recent insights into the creatine kinase pathway, and provide rationale for dietary creatine supplementation in human ischemic and inflammatory pathologies.

Highlights

Creatine (Cr) plays a pivotal role in cellular energy homeostasis, in tissues with highly dynamic energy demands such as the brain, striated muscle and the gut
The Cr/creatine kinase (CK) circuit is tightly linked to mitochondrial structure and energetics, as MitCK is coupled to adenosine triphosphate (ATP) export via the adenine nucleotide transporter (ANT), and to ATP synthesis and respiratory chain activity
Heritable defects in Cr biosynthesis (AGAT, guanidinoacetate methyltransferase (GAMT)) and Cr transport (SLC6A8) have been identified and are Creatine, the intestinal barrier and inflammatory bowel disease Cytosolic brain creatine kinase (CKB) is prominently expressed in smooth muscle and epithelial cells of the human intestine [28], and immunolocalization studies indicate retention of the Na+Cl− dependent Cr transporter selectively to the enterocyte apical membrane [29]

Summary

Introduction

Creatine (Cr) plays a pivotal role in cellular energy homeostasis, in tissues with highly dynamic energy demands such as the brain, striated muscle and the gut. Heritable defects in Cr biosynthesis (AGAT, GAMT) and Cr transport (SLC6A8) have been identified and are Creatine, the intestinal barrier and inflammatory bowel disease Cytosolic CKB is prominently expressed in smooth muscle and epithelial cells of the human intestine [28], and immunolocalization studies indicate retention of the Na+Cl− dependent Cr transporter selectively to the enterocyte apical membrane [29].

Results

Conclusion