The pentose pathway: A random harvest

Williams, John F.; Arora, Krishan; Longenecker, John P.

doi:10.1016/0020-711x(87)90239-4

Cited by 46 publications

(20 citation statements)

References 257 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, attempts at identifying a mammalian ortholog have been unsuccessful. Alternatively, SBP has also been reported to function in an alternative “L-type” PPP in liver that eventually feeds into the nonoxidative arm (Williams et al, 1987). Our finding provides a unique connection of this pathway to a driver oncogene and may provide a novel diagnostic and therapeutic avenue for these Ras-driven tumors.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism

Ying

Kimmelman

Lyssiotis

et al. 2012

Cell

1,699

1,697

View full text Add to dashboard Cite

SUMMARY Tumor maintenance relies on continued activity of driver oncogenes, although their rate-limiting role is highly context dependent. Oncogenic Kras mutation is the signature event in pancreatic ductal adenocarcinoma (PDAC), serving a critical role in tumor initiation. Here, an inducible KrasG12D-driven PDAC mouse model establishes that advanced PDAC remains strictly dependent on KrasG12D expression. Transcriptome and metabolomic analyses indicate that KrasG12D serves a vital role in controlling tumor metabolism through stimulation of glucose uptake and channeling of glucose intermediates into the hexosamine biosynthesis and pentose phosphate pathways (PPP). These studies also reveal that oncogenic Kras promotes ribose biogenesis. Unlike canonical models, we demonstrate that KrasG12D drives glycolysis intermediates into the nonoxidative PPP, thereby decoupling ribose biogenesis from NADP/NADPH-mediated redox control. Together, this work provides in vivo mechanistic insights into how oncogenic Kras promotes metabolic reprogramming in native tumors and illuminates potential metabolic targets that can be exploited for therapeutic benefit in PDAC.

show abstract

Section: Discussionmentioning

confidence: 99%

Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism

Ying

Kimmelman

Lyssiotis

et al. 2012

Cell

1,699

1,697

View full text Add to dashboard Cite

show abstract

“…Interestingly, the proposed reactions of the nonoxidative PPP are not firmly established; experimentally measured degree of 14 C isotope labelling and its distribution in carbon atoms of fructose-6-phosphate differs from that predicted by reaction sequences (Horecker et al, 1954;Williams et al, 1987;Schenk et al, 1998). This discrepancy demonstrates the presence of other types of nonoxidative PPP reactions, although the molecular and biochemical basis of these reactions remain elusive.…”

Section: Discussionmentioning

confidence: 99%

Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted

et al. 2006

View full text Add to dashboard Cite

Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic properties, which are likely to be caused by the internal deletion of conserved residues. We propose that TKTL1 upregulation in tumours leads to enhanced, oxygen-independent glucose usage and a lactatebased matrix degradation. As inhibition of transketolase enzyme reactions suppresses tumour growth and metastasis, TKTL1 could be the relevant target for novel anti-transketolase cancer therapies. We suggest an individualised cancer therapy based on the determination of metabolic changes in tumours that might enable the targeted inhibition of invasion and metastasis.

show abstract

“…This table is limited to the reactions that yield reaction products with a length of at least et al (1989) and by Williams et al (1987), but were only experimentally observed in small quantities in liver tissue, erythrocytes, and higher plants.…”

Section: Pitfall I: Incomplete Metabolic Reaction Modelsmentioning

confidence: 95%