Metabolic Applications of High-Resolution 13c Nuclear Magnetic Resonance Spectroscopy

Quantitative fMRI and oxidative neuroenergetics

“…Pioneering studies by Shulman and colleagues, originally at Bell Laboratories and later at Yale, showed that 13 C MRS had the potential to provide detailed measurements of metabolic fluxes (for a historical perspective see (Alger and Shulman, 1984)). Following initial studies in the late 1970’s in cell suspensions and perfused organs, the 13 C MRS method, and a related 1 H MRS method called proton observe carbon edit (POCE), was applied to the rodent and human brain (Behar et al, 1986; Cerdan et al, 1990; Fitzpatrick et al, 1990; Gruetter et al, 1992; Petroff et al, 1986; Rothman et al, 1985; Rothman et al, 1992).…”

Real or Imaginary? Human Metabolism through Nuclear Magnetism

“…In the isolated perfused rat liver, 15 NH 4 Cl, ornithine, and lactate generate 15 N-urea. 15 N-NMR is able to demonstrate the end product and the nitrogen intermediates-glutamate, glutamine, alanine, argininosuccinate, and citrulline (Fig. 3)-and so permits study of regulatory steps of the cycle in the intact organ.…”

“…This study, which is still in progress, addresses one of Krebs' other great interests, the role of glutamine and the activity of glutamate transaminase, work that was originally performed in kidney slices (9). In the brain, 15 NH C 4 is incorporated into glutamine by glutamine synthetase, an enzyme found exclusively in astrocytes. In the intact brain, ux rates for glutamine synthesis, glutaminase, glutamate dehydrogenase , and transaminase all appear to be only 1-2% of that for their respective isolated enzymes when the latter are provided with optimum amounts of (known) cofactors ( Fig.…”

Functional Magnetic Resonance Imaging in Medicine and Physiology

“…However, some metabolites may show dramatic differences in concentration upon alteration in physiology or function. For instance, lactate, phosphocreatine, free phosphate, and adenosine triphosphate (ATP) change by an order of magnitude in concentration in early stages of ischemia (43,44). Since these metabolites are easily identified by the particular chemical shift (Eq.…”

“…Other nuclei may provide alternative or additional information. For instance, proton NMR may reveal concentrations of neurotransmitters, osmolites, and glycolysis products (44). Labeling with the nonradioactive 13C nucleus (44) may be used to unravel biochemical pathways in vivo, similar to conventional labeling with the radioactive 14C nucleus used in other techniques.…”