Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway
The goal of this work is to investigate the potential for and limitations of in vivo nuclear magnetic resonance (NMR) spectroscopy for quantitation of glucose flux through the pentose phosphate pathway (shunt). Interest in the shunt is motivated by the possibility that its activity may be greatly increased in cancer and in the pathological states of cardiac and cerebral ischemia. The ability to dynamically monitor flux through the pentose shunt can give new knowledge about metabolism in pathological states. {sup 13}C NMR spectroscopy was used to monitor shunt activity by determination of the ratios of ({sup 13}C-4) to ({sup 13}C-5)-glutamate, ({sup 13}C-3) to ({sup 13}C-2)-alanine or ({sup 13}C-3) to ({sup 13}C-2)-lactate produced when ({sup 13}C-2)-glucose is infused. These methods provide measures of the effect of oxidative stresses on shunt activity in systems ranging from cell free enzyme-substrate preparations to cell suspensions and whole animals. In anaerobic cell free preparations, the fraction of glucose flux through the shunt was monitored with a time resolution of 3 minutes. This work predicts the potential for in vivo human studies of pentose phosphate pathway activity based on the mathematical simulation of the {sup 13}C fractional enrichments of C4 and C5-glutamate as a function of shunt activity and on the signal-to- noise ratio acquired in {sup 13}C NMR human studies from the current literature.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE; DOHHS; USDOE, Washington, DC (United States); Department of Health and Human Services, Washington, DC (United States)
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 5313663
- Report Number(s):
- LBL-31592; ON: DE92010257; CNN: HL07367
- Resource Relation:
- Other Information: Thesis (Ph.D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
75 CONDENSED MATTER PHYSICS
SUPERCONDUCTIVITY AND SUPERFLUIDITY
BRAIN
BIOCHEMISTRY
GLUCOSE
METABOLISM
PENTOSES
AEROBIC CONDITIONS
ALANINES
CARBON 13
IN VIVO
LACTATES
NEOPLASMS
NUCLEAR MAGNETIC RESONANCE
RATS
YEASTS
ALDEHYDES
AMINO ACIDS
ANIMALS
BODY
CARBOHYDRATES
CARBON ISOTOPES
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHEMISTRY
DISEASES
EUMYCOTA
EVEN-ODD NUCLEI
FUNGI
HEXOSES
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MAMMALS
MICROORGANISMS
MONOSACCHARIDES
NERVOUS SYSTEM
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PLANTS
RESONANCE
RODENTS
SACCHARIDES
STABLE ISOTOPES
VERTEBRATES
550500* - Metabolism
550200 - Biochemistry
665100 - Nuclear Techniques in Condensed Matter Physics - (1992-)