Six fucose‐α(1–2) sugars and α‐fucose assigned in the human brain using in vivo two‐dimensional MRS

Abstract

A growing body of literature has indicated that fucose-α(1-2)-galactose sugars are implicated in the molecular mechanisms that underlie neuronal development, learning and memory in the human brain. An understanding of the in vivo roles played by these terminal fucose residues has been hampered by the lack of technology to non-invasively monitor their levels in the human brain. We have implemented in vivo two-dimensional MRS technology to examine the human brain in a 3-T clinical MR scanner, and report that six fucose-α(1-2)-galactose residues and free α-fucose are available for inspection. Fucose-α(1-3)-galactose residues cannot yet be assigned using this technology as they resonate under the water resonance. This new application offers an unprecedented insight into the molecular mechanisms by which fucosylated sugars contribute to neuronal processes and how they alter during development, ageing and disease.

Diurnal variability of cerebral metabolites in healthy human brain with 2D localized correlation spectroscopy (2D L‐COSY)

“…Changes in fucose levels (0700–1700) is also worth mentioning, as we noted an increase in fucose in the afternoon (+23.4%). The glycosylation of various sugars is complex and a previous 2D L‐COSY study identified six different types of fucose residues with variation from person to person according to age and health state . We did not find any diurnal variation with GABA concentrations and this validates the study by Evans et al that time of day had no bearing on GABA levels from two brain regions .…”

“…The glycosylation of various sugars is complex and a previous 2D L-COSY study identified six different types of fucose residues with variation from person to person according to age and health state. 30 We did not find any diurnal variation with GABA concentrations and this validates the study by Evans et al that time of day had no bearing on GABA levels from two brain regions. 19 GSH, Hca, and lipids/MM are other metabolites that showed significant variations during the 10-hour period from morning to evening.…”

Reliability of neurometabolite detection with two‐dimensional localized correlation spectroscopy at 3T

“…Thus, 2D L‐COSY still remains the technique of choice for the detection of J‐coupled metabolite and improved spectral dispersion . Low concentration metabolites such as GABA, GSH, glucose, and fucose have been found to be biomarkers for many neurological disorders . 2D L‐COSY has a great potential in detecting these important low concentration metabolites with higher confidence.…”

“…27 Low concentration metabolites such as GABA, GSH, glucose, and fucose have been found to be biomarkers for many neurological disorders. 2,11,42,44,45 2D L-COSY has a great potential in detecting these important low concentration metabolites with higher confidence.…”

Safety evaluation of the human-identical milk monosaccharide, l-fucose

“…This is due particularly in light of the results of a number of studies indicating a role for fucosylation in cognitive function, learning, and memory Matthies et al, 1996;Murrey and Hsieh-Wilson, 2008;Mountford et al, 2014). L-Fucose is highly enriched at neuronal synapses (Murrey et al, 2006), where the majority of the fucosylated glycoconjugates exist as complex Nlinked glycoprotein structures.…”