Changes in glucose metabolism

Wartburg Effect

It was observed in tumoral cells by Otto Warburg and his colleagues in the 1920’s, the increase in

glycolysis continue to be even in presence of high O2, some explications could be that the ATP

required for proliferation is less than the needed for normal maintenance; there is a limit in the

mitochondrial production that is reached and the production of ATP is the same by either

glycolysis or oxidative phosphorylation because of the shorter time of glycolysis. The

consequences of the Warburg effect are around the increase in glycolysis; The pyruvate is

converted to lactate due to the lower flux to Krebs Cycle, leading to acidification which causes

damage to the stroma and space for proliferation, and production of NADH; Intermediaries on the

glycolysis can be used for anabolic purposes, Pentose Phosphate Pathway is an example that

produces ribose and NADPH2 which are used to cell division; Signalization pathways are present

in high glycolysis like: Production of ROS that are related to OIS and to avoid cellular damages

NADPH2 is consumed, Chromatin suffer changes by acetylation of histones with Acetyl CoA

and deacetylation of histones with Nutrient Stress; Protection against the Immune System is

given by the lower glycolysis flux of the Tumor Infiltrated Lymphocytes that reduces their

activity. Incongruences with these “beneficial” consequences of the Warburg Effect are: Lactate

is were all the Carbons end, instead of intermediaries and the NADH produced must be

consumed to keep glycolysis flux; Proteins required to high glycolysis flux are more than the

needed for cellular division; Intermediaries for biosynthesis can also be obtained from Krebs

Cycle; The Signalization pathways presented are difficult to confirm because of their indirect

nature.
Exercise

There are two determinants in exercise which are related to the increase of the ATP use,

Duration, and Intensity. Duration can be short-term and long-term, in the first one the major ATP

source are Phosphocreatine and glycolysis, in the second one Oxidative Phosphorylation has a

bigger contribution. Intensity, in Low Intensity plasma Free Fatty Acids are used as major ATP

source, in Moderate Intensity The Intramuscular Triglyceride and glycogen/ IMTG start to be

more important and in High Intensity the Phosphocreatine is low and glycogen has an even

bigger role. The higher ATP consume in exercise produces metabolites like AMP, ADP, Lactate

and ROS. The energy sources in exercise are glucose, lipids, and Phosphocreatine; glucose can

come from glycogen or blood stream, normally it comes from gluconeogenesis and

glycogenolysis in liver, but if there have been a meal recently gut can also provide; Lipids can be

obtained from IMTG and blood stream. The Uptake of these sources is increased with GLUT4

for glucose and FATP, FAT/CD36, FABpm for lipids, the lipases activity is also increased.

Calcium, metabolites and other can cause the Uptake increase by AKT pathway, AMPK

pathway and enzymes activity.

References

 Hargreaves M, Spriet LL. Exercise Metabolism: Fuels for the Fire. Cold Spring Harb

Perspect Med. 2018 Aug 1;8(8):a029744. doi: 10.1101/cshperspect.a029744. PMID:

28533314; PMCID: PMC6071548.

 Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells?

Trends Biochem Sci. 2016 Mar;41(3):211-218. doi: 10.1016/j.tibs.2015.12.001. Epub

2016 Jan 5. Erratum in: Trends Biochem Sci. 2016 Mar;41(3):287. Erratum in:

Trends Biochem Sci. 2016 Mar;41(3):287. PMID: 26778478; PMCID: PMC4783224.