Figure 1

Metabolic scheme. Carbon flow from [U-¹³C]-glucose through glycolysis, Krebs cycle, PPP, pyruvate carboxylation, malate/Asp shuttle, and synthesis of GSH and pyrimidine nucleotides as discussed in the text. Also shown are the expected ¹³C isotopomers of key metabolites in this network. Excretion of lactate and Ala into serum is part of the alanine and Cori cycles. Solid oval represents the plasma membrane and the dashed oval represents the mitochondrial space. Double-headed arrows: exchange or reversible processes. The label patterns arise from [U-¹³C]-glucose. Open circles: ¹²C; filled circles: ¹³C. Glc = glucose, G6P = glucose-6-phosphate, Rib = nucleotide ribose, DHAP, GAP = dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, PEP = phosphoenolpyruvate, Pyr = pyruvate, Lac = lactate, Cit = citrate, 2 = OG = 2-oxoglutarate, Mal = malate, OAA = oxalacetate, U = uracil base. Critical enzymes are shown in cyan. HK= hexokinase (entry to glycolysis), G6PDH = glucose-6-phosphate dehydrogenase (entry to the oxidative branch of the pentose phosphate pathway), TK, TA transketolase and transaldolase (non-oxidative pentose phosphate pathway), PK = pyruvate kinase, PDH = pyruvate dehydrogenase, PC = pyruvate carboxylase, AAT = aspartate amino transferase, MDH = malate dehydrogenase, ME = malic enzyme. Glutaminolysis is the pathway from Gln to pyruvate via ME, leading to unlabeled malate, Asp, Ala and lactate. Where two patterns are shown in the Krebs' cycle intermediates, this is due to the scrambling at the succinate step (first turn only). For U and OAA, the labeling from PC activity gives rise to a third labeling pattern, shown in red. The isotopomer pattern for U shows the three ring carbons (4,5,6) derived from Asp. The exchange of [¹³C-1,2,3]-Asp via the malate/Asp shuttle into the cytosol leads to the synthesis of [¹³C-1,2,3]-malate.