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Metabolic Stability of 3‐ O ‐Methyl‐d‐Glucose in Brain and Other Tissues
Author(s) -
Jay Thérèse M.,
Dienel Gerald A.,
Cruz Nancy F.,
Mori Kentaro,
Nelson Thomas,
Sokoloff Louis
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb04588.x
Subject(s) - hexokinase , biochemistry , in vivo , metabolism , yeast , medicine , endocrinology , biology , chemistry , glycolysis , microbiology and biotechnology
3‐ O ‐Methyl‐d‐glucose (methylglucose) is often used to study blood‐brain barrier transport and the distribution spaces of hexoses in brain. A critical requirement of this application is that it not be chemically converted in the tissues. Recent reports of phosphorylation of methylglucose by yeast and heart hexokinase have raised questions about its metabolic stability in brain. Therefore, we have re‐examined this question by studying the metabolism of methylglucose by yeast hexokinase and rat brain homogenates in vitro and rat brain, heart, and liver in vivo. Commercial preparations of yeast hexokinase did convert methylglucose to acidic products, but only when the enzyme was present in very large amounts. Methylglucose was not phosphorylated by brain homogenates under conditions that converted 97% of [U‐ 14 C]glucose to ionic derivatives. When [ 14 C]methylglucose, labeled in either the methyl or glucose moiety, was administered to rats by an intravenous pulse or a programmed infusion that maintained the arterial concentration constant and total 14 C was extracted from the tissues 60 min later, 97–100% of the 14 C in brain, >99% of the 14 C in plasma, and >90% of that in heart and liver were recovered as unmetabolized [ 14 C]methylglucose. Small amounts of 14 C in brain (1–3%), heart (3–6%), and liver (4–7%) were recovered in acidic products. Plasma glucose levels ranging from hypoglycemia to hyperglycemia had little influence on the degree of this conversion. The distribution spaces for methylglucose were found to be 0.52 in brain and heart and 0.75 in liver.