Sources of Glucose

Oral administration of 2H2O to enrich body water with 2H at a low level (~ 5%%) is used to determine the relative contribution of different sources to plasma glucose production. Glucose can be formed as a result of glycogen breakdown or synthesis from glycerol and pyruvate. The pathway of gluconeogenesis from pyruvate involves oxaloacetate (OAA) and hence the citric acid cycle.

sources-glucose-1

Site of proton exchange with deuterium occurring in the pathway of glucose production. The appearance of deuterium in the glucose molecule occurs as a result of proton-deuterium exchange with enriched water at certain points during its synthesis. Specific protons replaced in the intermediates leading up to glucose can be traced to different protons in the glucose molecule.

The site and extent of deuterium exchange is determined using 2H NMR spectroscopy. Measurements of the fractional amount of deuterium present at specific carbons can be used to measure the relative contribution of the different sources. Please see Human Applications for more details.

sources-glucose-2

2H NMR spectrum of deuterated glucose. The relative areas of the peaks corresponding to D2 (representing glucose from all sources), D5 (glucose from glycerol) and D6(S) (glucose produced from PEP, phosphoenol-pyruvate) can be used to calculate the fractional contribution of each source to glucose.