The pentose phosphate pathway (PPP) branches from glucose 6-phosphate (G6P), produces NADPH and ribose 5-phosphate (R5P), and shunts carbons back to the glycolytic or gluconeogenic pathway. The PPP has been demonstrated to be a major regulator for cellular reduction-oxidation (redox) homeostasis and biosynthesis. Enzymes in the PPP are reported to play important roles in many human diseases. In this review, we will discuss the role of the PPP in type 2 diabetes and cancer.

Metabolic alterations underlying clear cell renal cell carcinoma (ccRCC) progression include aerobic glycolysis, increased pentose phosphate pathway activity and reduced oxidative phosphorylation. Phosphofructokinase (PFK), a key enzyme of the glycolytic pathway, has L, M, and P isoforms with different tissue distributions. The mRNA level of the platelet isoform of phosphofructokinase (PFKP) is reported to be up-regulated in ccRCC patients. However, it remains unclear whether PFKP plays an important role in promoting aerobic glycolysis and macromolecular biosynthesis to support cell proliferation in ccRCC. Here we found that the up-regulated PFKP became the predominant isoform of PFK in human ccRCC. Suppression of PFKP not only impaired cell proliferation by inducing cell cycle arrest and apoptosis, but also led to decreased glycolysis, pentose phosphate pathway and nucleotide biosynthesis, accompanied by activated tricarboxylic acid cycle in ccRCC cells. Moreover, we found that p53 activation contributed to cell proliferation and metabolic defects induced by PFKP knockdown in ccRCC cells. Furthermore, suppression of PFKP led to reduced ccRCC tumor growth in vivo. Our data indicate that PFKP not only is required for metabolic reprogramming and maintaining cell proliferation, but also may provide us with a valid target for anti-renal cancer pharmaceutical agents.

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BackgroundTwo experiments were conducted to estimate the net energy (NE) of corn, soybean meal, expeller-pressed rapeseed meal (EP-RSM) and solvent-extracted rapeseed meal (SE-RSM) using indirect calorimetry and to validate the NE of these four ingredients using pig growth performance.MethodsIn Exp.1, 24 barrows (initial BW = 36.4 ± 1.6 kg) were allotted to 1 of 4 diets which included a corn basal diet, a corn-soybean meal basal diet and two rapeseed meal diets containing 20% EP-RSM (9.5% ether extract) or SE-RSM (1.1% ether extract) substituted for corn and soybean meal. The design allowed the calculation of NE values of corn, soybean meal and rapeseed meals according to the difference method. In Exp.2, 175 growing pigs (initial BW = 36.0 ± 5.2 kg) were fed 1 of 5 diets for 28 d, with five pigs per pen and seven replications (pens) per treatment in order to validate the measured energy values. Diets were a corn-soybean meal diet and four diets including 10% or 20% EP-RSM and 10% or 20% SE-RSM.ResultsThe NE of corn, soybean meal, EP-RSM and SE-RSM were 12.46, 11.34, 11.71 and 8.83 MJ/kg DM, respectively. The NE to ME ratio of corn (78%) was similar to tabular values, however, the NE to ME ratios of soybean meal (70%) and rapeseed meal (76%) were greater than tabular values. The greater NE value in EP-RSM than in SE-RSM is consistent with its higher EE content. Increasing EP-RSM or SE-RSM did not affect the growth performance of pigs and the caloric efficiency of NE was comparable for all diets.ConclusionsThe NE of EP-RSM was similar to soybean meal, and both were greater than SE-RSM. The DE, ME and NE values measured in Exp.1 are confirmed by results of Exp. 2 with comparable caloric efficiencies of DE, ME or NE for all diets.