The effect of orotic acid treatment on the energy and carbohydrate metabolism of the hypertrophying rat heart

Improvement of the energy supply and contractile function in normal and ischemic rat hearts by dietary orotic acid

“…For this concept, the modular organization of the processes of energy production, consumption and distribution obeys the spatial distribution of enzymatic systems within the cardiomyocyte, so that the glycolytic enzymes, linked to sarcolemma, are associated with channels and transporters of ions of the membrane. Our data corroborate previous works, by showing that glycolytic flux was "more open", permitting greater throughput of intermediates with individually increased levels of selected metabolites (Donohoe et al, 1993).…”

“…Previous studies have shown that the increase in contraction activates protein kinase D (PKD) in cardiac myocytes independently of AMPK signaling, and that the PKD activation is linked to contraction-induced GLUT4 translocation and GLUT4-mediated increase in glucose uptake (Luiken et al, 2008). Other possibility is that increased supply of intermediates for the synthesis of myocardial ATP by orotic acid (Donohoe et al, 1993) provides enough cellular ATP levels to decrease the AMP:ATP ratio and consequent activation of AMPK.…”

“…Other studies have shown that treatment of rats with OA increased the glycogen content of normoxic and ischemic hearts, with significant improvement in post-ischemic myocardial function (Ferdinandy et al, 1998;Munsch et al, 1989) and have suggested that synthesis of ATP and total adenine nucleotides can occur by stimulation of glucose uptake, via uridine, and consequent glycolysis for anaerobic production of energy (Donohoe et al, 1993). The challenge is, therefore, to optimize cardiac energetic yield, enabling the tissue to minimize the post-ischemia and reperfusion intracellular ionic overload and to ensure the vital cardiac functions.…”

Myocardial Infarct Size-Limiting and Anti-Arrhythmic Effects of Mildronate Orotate in the Rat Heart

“…The effect of orotic acid was also shown for myocardial degeneration and the development of congestive heart failure in cardiomyopathic hamsters of the UMX7.1 line, where it prolonged survival of the experimental animals [30]. The above mentioned effects are thought to be afforded by improved energy status in infracted or hypertrophying heart [31,32].…”

Metabolic therapy: cardioprotective effects of orotic acid and its derivatives

“…As a consequence, the activation of ribose-5-P formation via reversal of the Ltype pentose pathway in the heart will increase the PRPP generation whose concentration regulates both de novo and the salvage pathways for adenine nucleotide synthesis; the subsequent augmentation of adenylates (AMP, ADP) concentration will further increase the ATP availability, and (iv) the predominant use of the pyrimidine salvage pathway in the heart together with the enhanced production of pyrimidine bases in organs distant from the heart spares myocardial PRPP for the more dominant de novo adenine nucleotide synthesis (16). These latter authors demonstrated the ability of OA treatment to "energize" cardiomyocytes evaluated by the phosphorylation state of the adenine nucleotides, a parameter that is considered the best predictive index of the cellular energy status in normal and hypertrophying hearts (17).…”