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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ATP metabolism is controlled mainly by ATP synthase (ATP(ase)) and creatine kinase (CK) reactions that regulate cerebral ATP production, transportation, and utilization. These coupled reactions constitute a chemical exchange metabolic network of PCr<-->ATP<-->Pi characterized by two forward and two reverse reaction fluxes, which can be studied noninvasively by in vivo (31)P MRS combined with magnetization transfer (MT). However, it is still debated whether current MT approaches can precisely determine all of these fluxes. We developed and tested a modified in vivo (31)P MT approach based on a multiple single-site saturation (MSS) technique to study the entire PCr<-->ATP<-->Pi network in human occipital lobe at 7T. Our results reveal that 1) the MSS MT approach can explicitly determine all four reaction fluxes with a minimal number of (31)P spectra; 2) the three-spin exchange model accurately determines reverse reaction fluxes, resulting in equal forward and reverse fluxes for both CK and ATP(ase) reactions; and 3) the ATP synthesis rate (8.8 +/- 1.9 micromol/g/min, N = 11) measured in the human brain reflects cerebral oxidative phosphorylation. The MSS MT approach should provide an important modality for noninvasively studying the essential roles of ATP metabolism in brain bioenergetics, function, and diseases.
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PMID:Efficient in vivo 31P magnetization transfer approach for noninvasively determining multiple kinetic parameters and metabolic fluxes of ATP metabolism in the human brain. 1719 Dec 26

A new method for measuring spin-lattice relaxation times and chemical exchange (CE) rate constants in multiple-site exchanging systems is described. The method, chemical exchange and T(1) measurement using progressive saturation (CUPS), was applied to determine T(1)s and analyze phosphorus exchange among phosphocreatine (PCr), ATP, and inorganic phosphate (Pi), mediated by creatine kinase (CK) and ATP synthase, using (31)P-MRS. Two-site exchange was analyzed in vitro and in the rat leg, and three-site exchange was analyzed in the rat heart. Data were fitted to a model of progressive saturation incorporating T(1) relaxation and CE. For the in vitro system at 8.45 T, we found T(1)(PCr)=2.86 s and T(1)(gamma-ATP)=1.72 s. For the rat gastrocnemius at 1.9T, we found T(1)(PCr) = 6.60 s and T(1)(gamma-ATP) = 2.06 s. For the rat heart at 9.4 T, we found T(1)(PCr)=3.35 s, T(1)(gamma-ATP)=0.69 s, and T(1)(Pi=1.83 s. All of these values were within 20% of literature values. Similarly, the determined exchange rates were in the same range as published values. Using simulations, we compared CUPS with transient saturation transfer as a method for measuring T(1)s and rates. The two methods showed similar sensitivity to noise. We conclude that CUPS is a viable alternative for measuring T(1)s and CE rates in exchanging systems.
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PMID:Measurement of spin-lattice relaxation times and chemical exchange rates in multiple-site systems using progressive saturation. 1765 23

Impairment of energy metabolism is a key feature of Huntington disease (HD). Recently, we reported longitudinal neurochemical changes in R6/2 mice measured by in-vivo proton magnetic resonance spectroscopy ((1)H MRS; Zacharoff et al, 2012). Here, we present similar (1)H MRS measurements at an early stage in the milder Q111 mouse model. In addition, we measured the concentration of ATP and inorganic phosphate (P(i)), key energy metabolites not accessible with (1)H MRS, using (31)P MRS both in Q111 and in R6/2 mice. Significant changes in striatal creatine and phosphocreatine were observed in Q111 mice at 6 weeks relative to control, and these changes were largely reversed at 13 weeks. No significant change was detected in ATP concentration, in either HD mouse, compared with control. Calculated values of [ADP], phosphorylation potential, relative rate of ATP synthase (v/V(max)(ATP)), and relative rate of creatine kinase (v/V(max)(CK)) were calculated from the measured data. ADP concentration and v/V(max)(ATP) were increased in Q111 mice at 6 weeks, and returned close to normal at 13 weeks. In contrast, these parameters were normal in R6/2 mice. These results suggest that early changes in brain energy metabolism are followed by compensatory shifts to maintain energetic homeostasis from early ages through manifest disease.
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PMID:Homeostatic adaptations in brain energy metabolism in mouse models of Huntington disease. 2280 74