Biochemical characterization of muscle tissue of limb girdle muscular dystrophy: An ¹H and ¹³C NMR study

Abstract

The metabolic differences between the muscle biopsies of patients with limb girdle muscular dystrophy (LGMD) and normal controls were characterized using high-resolution 1H and 13C NMR spectroscopy. In all, 44 metabolites were unambiguously assigned in the perchloric acid extracts of skeletal muscle tissue, using 2D double quantum filtered (DQF COSY), total correlation (TOCSY), and 1H/13C heteronuclear multiple quantum coherence (HMQC) spectroscopy. The concentrations of glycolytic substrate, glucose (p=0.03), gluconeogenic amino acids, glutamine (p=0.02) and alanine (p=0.009) together with glycolytic product, lactate (p=0.04), were found to be significantly lowered in LGMD patients as compared with controls. The reduction in the concentration of glucose may be attributed to the decrease in the concentration of gluconeogenic amino acids in the degenerated muscle. Reduction in the rate of anaerobic glycolysis and lowered substrate concentration appear to be the possible reasons for the decrease in the concentration of lactate. A significant reduction in the concentration of choline in LGMD patients was also observed compared with controls. Lower concentration of choline may be the result of decreased rate of membrane turnover in LGMD patients. The data presented here provide an insight into the potentials of in-vitro NMR spectroscopy in the study of muscle metabolism.

Advancements in magnetic resonance imaging‐based biomarkers for muscular dystrophy

“…Sodium ( 23 Na) spectroscopy, for instance, can be used to examine osmotic properties and ion homeostasis in skeletal muscle in DMD . Carbon ( 13 C) spectroscopy can also be used to study glycolytic pathway elements in muscle but has not yet been extensively studied in vivo in the muscular dystrophy population …”

“…88,89 Carbon ( 13 C) spectroscopy can also be used to study glycolytic pathway elements in muscle but has not yet been extensively studied in vivo in the muscular dystrophy population. 90,91…”

First experience of compressible gas dynamics simulation on the Los Alamos roadrunner machine

“…DMD, the most severe muscular dystrophy, showed more severe metabolic alterations compared to healthy volunteers than BMD and LGMD patients 26. A similar suggestion was made for metabolic differences between DMD and LGMD patients as uncovered by in vitro 1 H MRS 27, 28. As explained above, clinically it is difficult to assess involvement of individual muscles, except for a few specific ones like the TA muscle.…”

In vivo 2D magnetic resonance spectroscopy of small animals

“…Among these 2D studies, there are almost more publications about studies in man (COSY tissues extracts [126]; DQF-COSY and/or TOCSY tissues extracts [127,128]; muscle biopsy [129,130] and in vivo localized 2D J spectroscopy and/or DQF constant-time COSY on human Anterior Tibialis [32,131]; and VOSY-COSY [69]) than in small animals.…”