Abstract
Aerobic glycolysis or the Warburg effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although the WE is ubiquitous, its biological role remains controversial, and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, here we evolved resistance to koningic acid (KA), a natural product that specifically inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme, during the WE. We found that KA-resistant cells lose theWEbut continue to conduct glycolysis and surprisingly remain dependent on glucose as a carbon source and also on central carbon metabolism. Consequently, this altered state of glycolysis led to differential metabolic activity and requirements, including emergent activities in and dependences on fatty acid metabolism. These findings reveal that aerobic glycolysis is a process functionally distinct from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 111-124 |
| Number of pages | 14 |
| Journal | Journal of Biological Chemistry |
| Volume | 295 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2020 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Evolved resistance to partial GAPDH inhibition results in loss of the Warburg effect and in a different state of glycolysis. / Liberti, Maria V.; Allen, Annamarie E.; Ramesh, Vijyendra; Dai, Ziwei; Singleton, Katherine R.; Guo, Zufeng; Liu, Jun O.; Wood, Kris C.; Locasale, Jason W.
In: Journal of Biological Chemistry, Vol. 295, No. 1, 01.01.2020, p. 111-124.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evolved resistance to partial GAPDH inhibition results in loss of the Warburg effect and in a different state of glycolysis
AU - Liberti, Maria V.
AU - Allen, Annamarie E.
AU - Ramesh, Vijyendra
AU - Dai, Ziwei
AU - Singleton, Katherine R.
AU - Guo, Zufeng
AU - Liu, Jun O.
AU - Wood, Kris C.
AU - Locasale, Jason W.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Aerobic glycolysis or the Warburg effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although the WE is ubiquitous, its biological role remains controversial, and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, here we evolved resistance to koningic acid (KA), a natural product that specifically inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme, during the WE. We found that KA-resistant cells lose theWEbut continue to conduct glycolysis and surprisingly remain dependent on glucose as a carbon source and also on central carbon metabolism. Consequently, this altered state of glycolysis led to differential metabolic activity and requirements, including emergent activities in and dependences on fatty acid metabolism. These findings reveal that aerobic glycolysis is a process functionally distinct from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions.
AB - Aerobic glycolysis or the Warburg effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although the WE is ubiquitous, its biological role remains controversial, and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, here we evolved resistance to koningic acid (KA), a natural product that specifically inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme, during the WE. We found that KA-resistant cells lose theWEbut continue to conduct glycolysis and surprisingly remain dependent on glucose as a carbon source and also on central carbon metabolism. Consequently, this altered state of glycolysis led to differential metabolic activity and requirements, including emergent activities in and dependences on fatty acid metabolism. These findings reveal that aerobic glycolysis is a process functionally distinct from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions.
UR - http://www.scopus.com/inward/record.url?scp=85077475427&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077475427&partnerID=8YFLogxK
U2 - 10.1074/jbc.RA119.010903
DO - 10.1074/jbc.RA119.010903
M3 - Article
C2 - 31748414
AN - SCOPUS:85077475427
VL - 295
SP - 111
EP - 124
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 1
ER -