Cardiac expression and location of hexokinase changes in a mouse model of pure creatine-deficiency.

Cardiac expression and location of hexokinase changes in a mouse model of pure creatine-deficiency. Am J Physiol Heart Circ Physiol. 2020 Dec 18;: Authors: Branovets J, Karro N, Barsunova K, Laasmaa M, Lygate CA, Vendelin M, Birkedal R Abstract Creatine kinase (CK) is considered the main phosphotransfer system in the heart, important for overcoming diffusion restrictions and regulating mitochondrial respiration. It is substrate limited in creatine-deficient mice lacking L-arginine:glycine amidinotransferase (AGAT) or guanidinoacetate methyltranferase (GAMT). Our aim was to determine the expression, activity and mitochondrial coupling of hexokinase (HK) and adenylate kinase (AK), as these represent alternative energy transfer systems. In permeabilized cardiomyocytes, we assessed how much endogenous ADP generated by HK, AK or CK stimulated mitochondrial respiration and how much was channeled to mitochondria. In whole heart homogenates, and cytosolic and mitochondrial fractions, we measured the activities of AK, CK and HK. Lastly, we assessed the expression of the major HK, AK and CK isoforms. Overall, respiration stimulated by HK, AK and CK was ~25, 90 and 80%, respectively, of the maximal respiration rate, and ~20, 0 and 25%, respectively, was channeled to the mitochondria. The activity, distribution and expression of HK, AK and CK did not change in GAMT KO mice. In AGAT KO mice, we found no changes in AK, but we found a higher HK act...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research