Huntington’s disease (HD) is a monogenic neurodegenerative disorder with a significant peripheral
component to the disease pathology. This includes an HD-related cardiomyopathy, with an unknown
pathological mechanism. In this study, we aimed to define changes in the metabolism of cardiac
nucleotides using the well-established R6/2 mouse model. In particular, we focused on measuring the
activity of enzymes that control ATP and other adenine nucleotides in the cardiac pool, including
eNTPD, AMPD, e5'NT, ADA and PNP. We employed HPLC to assay the activities of these enzymes by
measuring the concentrations of adenine nucleotide catabolites in the hearts of symptomatic R6/2 mice.
We found a reduced activity of AMPD (12.9 ± 1.9 nmol/min/mg protein in control; 7.5 ± 0.5
nmol/min/mg protein in R6/2) and e5'NT (11.9 ± 1.7 nmol/min/mg protein in control; 6.7 ± 0.7
nmol/min/mg protein in R6/2). Moreover, we detected an increased activity of ADA (1.3 ± 0.2
nmol/min/mg protein in control; 5.2 ± 0.5 nmol/min/mg protein in R6/2), while no changes in eNTPD
and PNP activities were detected. Analysis of cardiac adenine nucleotide catabolite levels revealed an
increased inosine level (0.7 ± 0.01 nmol/mg dry tissue in control; 2.7 ±0.8 nmol/mg dry tissue in R6/2)
and a reduced concentration of cardiac adenosine (0.9 ± 0.2 nmol/mg dry tissue in control; 0.2 ± 0.08
nmol/mg dry tissue in R6/2). This study highlights a decreased rate of degradation of cardiac nucleotides
in HD mouse model hearts, and an increased capacity for adenosine deamination, that may alter
adenosine signaling.