Trafficking of considerable amounts of arguably performance and/or body-enhancing compounds has been observed during the past 4 years, the majority of which is categorized as relevant to sports drug testing. Several substances are of fake/non-approved nature and represent enormous health risks to the 'customer'.
Diphospho-myo-inositol phosphates (PP-InsP5 and bis-PP-InsP4) were isolated from Dictyostelium in order to clarify the precise positional isomerism by two-dimensional 1H/31P-NMR analysis. The diphosphorylated inositol phosphates are 4-PP-Ins(1,2,3,5,6)P5 and 4,5-bis-PP-Ins(1,2,3,6)P4 or their corresponding enantiomers. The vicinal arrangement of the diphospho groups with its steric and electrostatic constraints possibly qualifies bis-PP-InsP4 as a metabolite with high phosphate-group-transfer potential in phosphotransferase reactions.
Two diphospho-myo-inositol phosphates from Dictyostelium were recently investigated by two-dimensional 1H/31P NMR analysis and assigned to be either D-4-diphospho-myo-inositol pentakisphosphate (D-4-PP-InsP5) and D-4,5-bisdiphospho-myo-inositol tetrakisphosphate (D-4,5-bis-PP-InsP4) or their corresponding enantiomers D-6-PP-InsP5 and D-5,6-bis-PP-InsP4. In the present study the naturally occurring enantiomers were identified by using defined synthetic PP-InsP5 isomers as substrates for a partially purified PP-InsP5 5-kinase from Dictyostelium. This enzyme specifically phosphorylates the naturally occurring PP-InsP5 and the synthetic D-6-PP-InsP5, leading to D-5,6-bis-PP-InsP4. In contrast, neither D-4-PP-InsP5 nor D-1-PP-InsP5 or D-3-PP-InsP5 are converted by the enzyme.
Abstract-Myoglobin is an important intracellular O 2 binding hemoprotein in heart and skeletal muscle. Surprisingly, disruption of myoglobin in mice (myo Ϫ/Ϫ ) resulted in no obvious phenotype and normal cardiac function was suggested to be mediated by structural alterations that tend to steepen the oxygen pressure gradient from capillary to mitochondria. Here we report that lack of myoglobin causes a biochemical shift in cardiac substrate utilization from fatty acid to glucose oxidation. Proteome and gene expression analysis uncovered key enzymes of mitochondrial -oxidation as well as the nuclear receptor PPAR␣ to be downregulated in myoglobin-deficient hearts. Using FDG-PET we showed a substantially increased in vivo cardiac uptake of glucose in myo Ϫ/Ϫ mice (6.7Ϯ2.3 versus 0.8Ϯ0.5% of injected dose in wild-type, nϭ5, PϽ0.001), which was associated with an upregulation of the glucose transporter GLUT4. The metabolic switch was confirmed by 13 C NMR spetroscopic isotopomer studies of isolated hearts which revealed that [1,[6][7][8][9][10][11][12][13] C 2 ]glucose utilization was increased in myo Ϫ/Ϫ hearts (38Ϯ8% versus 22Ϯ5% in wild-type, nϭ6, PϽ0.05), and concomitantly, [U-13 C 16 ]palmitate utilization was decreased in the myoglobin-deficient group (42Ϯ6% versus 63Ϯ11% in wild-type, nϭ6, PϽ0.05). Because of the O 2 -sparing effect of glucose utilization, the observed shift in substrate metabolism benefits energy homoeostasis and therefore represents a molecular adaptation process allowing to compensate for lack of the cytosolic oxygen carrier myoglobin. Furthermore, our data suggest that an altered myoglobin level itself may be a critical determinant for substrate selection in the heart. The full text of this article is available online at http://circres.ahajournals.org. (Circ Res. 2005;96:e68-e75.) Key Words: metabolism Ⅲ -oxidation Ⅲ glucose Ⅲ oxygen Ⅲ heart I t is well known that red and white muscle are not only characterized by a largely different content of myoglobin (Mb), but also by significant differences in metabolism closely related to their physiological function. 1,2 Red muscles exhibit slow twitch speed, are fatigue resistant, and have an aerobic fat-, glucose-, and ketone-based metabolism. In contrast, white muscle fibers are fast contracting anaerobic fibers and easily fatigued because they have few respiratory proteins and metabolize glucose only as far as lactate. Similar to the red skeletal muscle, the heart has a high, enduring energy demand, which under normal conditions is primarily met by metabolism of fatty acids (FAs). 3 Nevertheless, in several cardiac diseases, such as ischemic cardiomyopathy, heart failure, hypertrophy, and dilated cardiomyopathy, a reduced oxidation of FAs and an enhanced glucose utilization has been found. 4 Interestingly, dilated and ischemic cardiomyopathies have also been reported to be accompanied by a decreased myocardial Mb content. 5 However, whether there is more then a mere correlation between muscle Mb level and substrate metabolism has not been ex...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.