Abstract:
:Previous studies have demonstrated that using hyperpolarized [2-13 C]pyruvate as a contrast agent can reveal 13 C signals from metabolites associated with the tricarboxylic acid (TCA) cycle. However, the metabolites detectable from TCA cycle-mediated oxidation of [2-13 C]pyruvate are the result of several metabolic steps. In the instance of the [5-13 C]glutamate signal, the amplitude can be modulated by changes to the rates of pyruvate dehydrogenase (PDH) flux, TCA cycle flux and metabolite pool size. Also key is the malate-aspartate shuttle, which facilitates the transport of cytosolic reducing equivalents into the mitochondria for oxidation via the malate-α-ketoglutarate transporter, a process coupled to the exchange of cytosolic malate for mitochondrial α-ketoglutarate. In this study, we investigated the mechanism driving the observed changes to hyperpolarized [2-13 C]pyruvate metabolism. Using hyperpolarized [1,2-13 C]pyruvate with magnetic resonance spectroscopy (MRS) in the porcine heart with different workloads, it was possible to probe 13 C-glutamate labeling relative to rates of cytosolic metabolism, PDH flux and TCA cycle turnover in a single experiment non-invasively. Via the [1-13 C]pyruvate label, we observed more than a five-fold increase in the cytosolic conversion of pyruvate to [1-13 C]lactate and [1-13 C]alanine with higher workload. 13 C-Bicarbonate production by PDH was increased by a factor of 2.2. Cardiac cine imaging measured a two-fold increase in cardiac output, which is known to couple to TCA cycle turnover. Via the [2-13 C]pyruvate label, we observed that 13 C-acetylcarnitine production increased 2.5-fold in proportion to the 13 C-bicarbonate signal, whereas the 13 C-glutamate metabolic flux remained constant on adrenergic activation. Thus, the 13 C-glutamate signal relative to the amount of 13 C-labeled acetyl-coenzyme A (acetyl-CoA) entering the TCA cycle was decreased by 40%. The data strongly suggest that NADH (reduced form of nicotinamide adenine dinucleotide) shuttling from the cytosol to the mitochondria via the malate-aspartate shuttle is limited on adrenergic activation. Changes in [5-13 C]glutamate production from [2-13 C]pyruvate may play an important future role in non-invasive myocardial assessment in patients with cardiovascular diseases, but careful interpretation of the results is required.
journal_name
NMR Biomedjournal_title
NMR in biomedicineauthors
Chen AP,Lau AZ,Gu YP,Schroeder MA,Barry J,Cunningham CHdoi
10.1002/nbm.3845subject
Has Abstractpub_date
2018-01-01 00:00:00issue
1eissn
0952-3480issn
1099-1492journal_volume
31pub_type
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journal_title:NMR in biomedicine
pub_type: 杂志文章
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journal_title:NMR in biomedicine
pub_type: 杂志文章
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journal_title:NMR in biomedicine
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journal_title:NMR in biomedicine
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journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3950
更新日期:2018-11-01 00:00:00
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journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3110
更新日期:2014-06-01 00:00:00
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journal_title:NMR in biomedicine
pub_type: 杂志文章
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更新日期:2008-02-01 00:00:00
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journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.4135
更新日期:2019-11-01 00:00:00
abstract::Metabolic activity in the lung is known to change in response to external insults, inflammation, and cancer. We report measurements of metabolism in the isolated, perfused rat lung of healthy controls and in diseased lungs undergoing acute inflammation using hyperpolarized 1-(13) C-labeled pyruvate. The overall appare...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3139
更新日期:2014-08-01 00:00:00
abstract::To assess infarction development in pig hearts, Mn-enhanced and Gd-enhanced MRI were used. In domestic pigs (25-35 kg, n = 37), the first and second diagonal branches of the left anterior descending coronary artery were ligated to induce acute ischemia and infarction (ischemia+reperfusion) or chronic infarction of inc...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1297
更新日期:2009-02-01 00:00:00
abstract::The application of diffusion tensor imaging (DTI) to the evaluation of developing brain remains an area of active investigation. This review focuses on the changes in DTI parameters which accompany both brain maturation and injury. The two primary pieces of information available from DTI studies-water apparent diffusi...
journal_title:NMR in biomedicine
pub_type: 杂志文章,评审
doi:10.1002/nbm.784
更新日期:2002-11-01 00:00:00
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journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1470
更新日期:2010-05-01 00:00:00
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journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1614
更新日期:2011-06-01 00:00:00
abstract::Organs consist of several types of cells with specialized functions. This cellular localization of function is often referred to as compartmentation. Due to the intrinsic low sensitivity of MR methods it is generally not possible in vivo to obtain images or spectra of single cells. Instead the MRS signal is the sum of...
journal_title:NMR in biomedicine
pub_type: 杂志文章,评审
doi:10.1002/nbm.692
更新日期:2001-04-01 00:00:00
abstract::A novel iodoacetamide label 4-perfluoro-tert-butyl-phenyliodoacetamide (PFP) containing nine fluorine atoms in equivalent positions has been synthesized. It provides a homogeneous 19F NMR resonance line which can be detected with high sensitivity when coupled to proteins. As an example, the sulfhydryl groups of actin ...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1940050605
更新日期:1992-11-01 00:00:00
abstract::The aim of this study was to acquire high-quality in vivo (1) H spectra concurrently from two voxels at ultra-high field (7 T) without specialized hardware. To this end, an acquisition scheme was developed in which first-order shims and flip angles are dynamically updated to acquire spectra from both of the brain's mo...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3328
更新日期:2015-07-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2001-06-01 00:00:00
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journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3619
更新日期:2017-04-01 00:00:00
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doi:10.1002/nbm.3778
更新日期:2019-04-01 00:00:00
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更新日期:2015-11-01 00:00:00
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journal_title:NMR in biomedicine
pub_type: 杂志文章
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更新日期:2020-09-01 00:00:00
abstract::Elevated brain myo-inositol (m-Ins) concentration (a putative marker of neuroinflammation) has been reported in patients suffering from type 2 diabetes mellitus (T2DM). Obesity alone and T2DM have been found to be associated with a lower concentration of N-acetyloaspartate and N-acetylaspartylglutamate (tNAA, a marker...
journal_title:NMR in biomedicine
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doi:10.1002/nbm.3957
更新日期:2018-09-01 00:00:00
abstract::Dynamic contrast-enhanced MRI (DCE MRI) has been used to study tumor response to treatment for many years. In this study, the modified full width at half-maximum (mFWHM), calculated from the wash-in slope histogram, is proposed as a parameter for the evaluation of changes in tumor heterogeneity which respond to radiot...
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更新日期:2013-04-01 00:00:00
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journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/1099-1492(200008)13:5<297::aid-nbm648>3.0.
更新日期:2000-08-01 00:00:00
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journal_title:NMR in biomedicine
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更新日期:2000-11-01 00:00:00
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journal_title:NMR in biomedicine
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