caa a22 4500 477119522 CHVBK 20180405111632.0 cr unu---uuuuu 170330e19960301xx s 000 0 eng 10.1007/BF00240038 doi (NATIONALLICENCE)springer-10.1007/BF00240038 Zimmer Heinz-Gerd Carl-Ludwig-Institute of Physiology, University of Leipzig, Liebigstr. 27, D-04103, Leipzig, Germany aut Regulation of and intervention into the oxidative pentose phosphate pathway and adenine nucleotide metabolism in the heart [Elektronische Daten] [Heinz-Gerd Zimmer] The capacity of the oxidative pentose phosphate pathway (PPP) in the heart is limited, since the activity of glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of this pathway, is very low. Two mechanisms are involved in the regulation of this pathway. Under normal conditions, G-6-PD is inhibited by NADPH. This can be overcome in the isolated perfused rat heart by increasing the oxidized glutathione and by elevating the NADP+/NADPH ratio. Besides this rapid control mechanism, there is a long-term regulation which involves the synthesis of G-6-PD. The activity of G-6-PD was elevated in the rat heart during the development of cardiac hypertrophy due to constriction of the abdominal aorta and in the non-ischemic part of the rat heart subsequent to myocardial infarction. The catecholamines isoproterenol and norepinephrine stimulated the activity of myocardial G-6-PD in a time- and dose-dependent manner. The isoproterenol-induced stimulation was cAMP-dependent and due to increased new synthesis of enzyme protein. The G-6-PD mRNA was elevated by norepinephrine. As a consequence of the stimulation of the oxidative PPP, the available pool of 5-phosphoribosyl-l-pyrophosphate (PRPP) was expanded. PRPP is an important precursor substrate for purine and pyrimidine nucleotide synthesis. The limiting step in the oxidative PPP, the G-6-PD reaction, can be bypassed with ribose. This leads to an elevation of the cardiac PRPP pool. The decline in ATP that is induced in many pathophysiological conditions was attenuated or even entirely prevented by i.v. infusion of ribose. In two in vivo rat models, the overloaded and catecholamine-stimulated heart and the infarcted heart, the normalization of the cardiac adenine nucleotide pool by ribose was accompanied by an improvement of global heart function. Combination of ribose with adenine or inosine in isoproterenol-treated rats was more effective to restore completely the cardiac ATP level within a short period of time than either intervention alone. (Mol Cell Biochem 160/161: 101-109, 1996) Kluwer Academic Publishers, 1996 adenine nucleotide synthesis nationallicence catecholamines nationallicence cardiac hypertrophy nationallicence ischemic heart disease nationallicence 5-phosphoribosyl-l-pyrophosphate nationallicence ribose nationallicence Molecular and Cellular Biochemistry Kluwer Academic Publishers; http://www.wkap.nl 160-161/1(1996-03-01), 101-109 0300-8177 160-161:1<101 1996 160-161 11010 https://doi.org/10.1007/BF00240038 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00240038 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Zimmer Heinz-Gerd Carl-Ludwig-Institute of Physiology, University of Leipzig, Liebigstr. 27, D-04103, Leipzig, Germany aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers; http://www.wkap.nl 160-161/1(1996-03-01), 101-109 0300-8177 160-161:1<101 1996 160-161 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer