Biomedical subjects

P J Card

Publications and source records attributed to P J Card.

4 recordsLinked to original sources

PubMed1988

Fluorine-19 NMR imaging of glucose metabolism.

Metabolic imaging reflecting glucose metabolism in the glycolytic and aldose reductase sorbitol (ARS) pathways was performed noninvasively in rat using fluorinated glucose analogs, 2-fluoro-2-deoxy-D-glucose (2-FDG) or 3-fluoro-3-deoxy-D-glucose (3-FDG), and fluorine-19 (19F) nuclear magnetic resonance (NMR) imaging. 19F images of 2-FDG-6-phosphate, a main metabolite of 2-FDG in the glycolytic pathway, showed high glucose utilization in the brain, spinal cord, and heart. Images of 3-fluoro-3-deoxy-D-sorbitol (3-FDSL), a main metabolite of 3-FDG in the ARS pathway, demonstrated the heterogeneous nature of the spatial distribution of aldose reductase activities, being highest in the brain and lens. The extremely low toxicity of 3-FDG indicates promise for clinical application of 3-FDG NMR imaging.

Animals↗

PubMed1987

Noninvasive demonstration of in vivo 3-fluoro-3-deoxy-D-glucose metabolism in rat brain by 19F nuclear magnetic resonance spectroscopy: suitable probe for monitoring cerebral aldose reductase activities.

The metabolism of 3-fluoro-3-deoxy-D-glucose (3-FDG) in rat brain in vivo was investigated noninvasively using 19F nuclear magnetic resonance (NMR) spectroscopy. Following an intravenous infusion of 3-FDG, 400 mg/kg, four resonances assigned to the alpha and beta anomers of 3-FDG, 3-fluoro-3-deoxy-D-sorbitol, and 3-fluoro-3-deoxy-D-fructose were clearly resolved in brain, a result indicating that 3-FDG is metabolized primarily into the aldose reductase sorbitol (ARS) pathway. An orally administered aldose reductase inhibitor, sorbinil, caused reduction of the flux of 3-FDG into the ARS, an observation suggesting that the method can be applied in quantitative studies of ARS pathway activities. Studies of 24-h urine specimens showed that in addition to the two metabolites observed in brain, F- was excreted into the urine. 3-FDG appears to be a suitable metabolic probe for assessing glucose metabolism in the ARS pathway by in vivo 19F NMR spectroscopy.

Aldehyde Reductase↗

PubMed1986

Substrate recognition by a sucrose transporting protein.

Protoplasts derived from developing soybean cotyledons were used to study substrate recognition by a sucrose transporting protein in plant membranes. When used as alternate substrate inhibitors of [14C] sucrose influx, five different fructosyl-substituted sucrose derivatives, phenyl-alpha-D-glucopyranoside, and phenyl-alpha-D-thioglucopyranoside proved to bind effectively to the sucrose carrier-active site. These results are interpreted to indicate that a large portion of substrate recognition by this carrier may arise from the interaction of a relatively hydrophobic portion of the sucrose molecule and a hydrophobic region of the carrier protein binding site. Binding of phenyl-alpha-D-thioglucopyranosides in which various substitutions were made for the glucosyl hydroxyls shows that the glucosyl hydroxyls at positions 3, 4, and 6 are involved in substrate recognition by the carrier protein.

Carrier Proteins↗

PubMed1985

Transport and metabolism of 1'-fluorosucrose, a sucrose analog not subject to invertase hydrolysis.

The novel sucrose derivative 1'-fluorosucrose (alpha-d-glucopyranosyl-beta- d-1-deoxy-1-fluorofructofuranoside) was synthesized in order to help define mechanisms of sucrose entry into plant cells. Replacement of the 1'-hydroxyl by fluorine very greatly reduces invertase hydrolysis of the derivative (hydrolysis at 10 millimolar 1'-fluorosucrose is less than 2% that of sucrose) but does not reduce recognition, binding, or transport of 1'-fluorosucrose by a sucrose carrier. Transport characteristics of 1'-fluorosucrose were studied in three different tissues. The derivative is transported by the sucrose carrier in the plasmalemma of developing soybean cotyledon protoplasts with a higher affinity than sucrose (K(m) 1'-fluorosucrose 0.9 millimolar, K(m) sucrose 2.0 millimolar). 1'-Fluorosucrose is a competitive inhibitor of sucrose uptake with an apparent K(i) also of 0.9 millimolar, while the K(i) of sucrose competition of 1'-fluorosucrose uptake was 2.0 millimolar. Thus, both sugars are recognized at the same binding site in the plasmalemma. Both sucrose and 1'-fluorosucrose show very similar patterns of phloem translocation from an abraded leaf surface through the petiole indicating that recognition of 1'-fluorosucrose by sucrose carriers involved in phloem loading is likely as well.1'-Fluorosucrose is a very poor substrate for invertase and as such is absorbed only slowly by corn root segments, a tissue in which sucrose hydrolysis by a cell wall invertase is required prior to active hexose uptake.The kinetics of 1'-fluorosucrose uptake by soybean cotyledon protoplasts indicate that membrane passage and substrate release to the protoplast interior are rate limiting to transport. Recognition of sucrose at the inner membrane surface of the carrier protein is apparently different than recognition and binding at the external surface.

Journal Article↗