Major metabolic pathways of glucose in normal human lymphocytes and the effect of cortisol

Abstract

1. 1. Intact normal human lymphocytes were incubated in vitro with [1- 14C]-, [2- 14C]- and [6- 14C]glucose and the fate of 14C in the cells was followed. Parallel incubations with the addition of cortisol were performed. 2. 2. Glucose was catabolized mainly via the Embden-Meyerhof pathway and approx. 70% of utilized glucose was converted to lactate. The contribution of the pentose cycle to overall glucose metabolism was approx. 2% and recycling in the pentose cycle was demonstrated. Approx. 1% of utilized glucose was metabolized via the Krebs cycle. Of the utilized glucose label 2–4% was accounted for by glycogen- 14C and approx. 2% by 14C in supporting tissue. 14C incorporation into acetate was low and 14C activity in total lipids was extremely low. 3. 3. Degradations of glucose liberated from glycogen indicated an extensive operation of the transaldolase exchange mechanism and absence or very low activity of fructose 1,6-diphosphatase. The labeling pattern in the C-1, C-2 and C-3 positions of glucose obtained from glycogen, when the cells were incubated with [1- 14C]- and [2- 14C]glucose, suggested reversal of the pentose pathway. Observed discrepancies between randomization in lactate and glucose of glycogen could possibly be explained by assuming the existence of 2 separate glucose 6-phosphate pools. 4. 4. Cortisol inhibited glucose utilization. The relative contribution of glycogen synthesis, lactate formation, pentose cycle and Krebs cycle to overall glucose metabolism was unchanged by cortisol. Concomitantly total lactate production was no suppressed in the presence of cortisol, suggesting lactate formation from endogenous sources.