The aerobic glycolysis or aerobic defined as the use of excess glucose is not processed by oxidative phosphorylation to the formation of products "fermentative", even under conditions of high oxygen concentrations and despite the drop in energy efficiency.
It commonly occurs in tissues with high proliferative rates, whose consumption of glucose and oxygen is high. Examples of this are cancer tumor cells, some parasitic cells in the blood of mammals and even cells in some areas of the brain of mammals.
Glycolytic pathway (Source:] via Wikimedia Commons)
The energy extracted by the catabolism of glucose is conserved in the form of ATP and NADH, which are used downstream in various metabolic pathways.
During aerobic glycolysis, pyruvate is directed towards the Krebs cycle and the electron transport chain, but it is also processed through the fermentation pathway for the regeneration of NAD + without additional production of ATP, which ends with the formation of lactate.
Aerobic or anaerobic glycolysis occurs primarily in the cytosol, with the exception of organisms such as trypanosomatids, which possess specialized glycolytic organelles known as glycosomes.
Glycolysis is one of the best known metabolic pathways. It was completely formulated in the 1930s by Gustav Embden and Otto Meyerhof, who studied the pathway in skeletal muscle cells. However, aerobic glycolysis has been known as the Warburg effect since 1924.
Reactions
The aerobic catabolism of glucose occurs in ten enzymatically catalyzed steps. Many authors consider that these steps are divided into a phase of energy investment, which aims to increase the content of free energy in the intermediaries, and another of replacement and the gain of energy in the form of ATP.
Energy investment phase
1-Phosphorylation of glucose to glucose 6-phosphate catalyzed by hexokinase (HK). In this reaction, one molecule of ATP is inverted for each glucose molecule, which acts as a phosphate group donor. It yields glucose 6-phosphate (G6P) and ADP, and the reaction is irreversible.
The enzyme necessarily requires the formation of a complete Mg-ATP2- for its operation, which is why it requires magnesium ions.
2-Isomerization of G6P to fructose 6-phosphate (F6P). It does not involve energy expenditure and is a reversible reaction catalyzed by phosphoglucose isomerase (PGI).
3-Phosphorylation of F6P to fructose 1,6-bisphosphate catalyzed by phosphofructokinase-1 (PFK-1). A molecule of ATP is used as the phosphate group donor and the reaction products are F1,6-BP and ADP. Thanks to its value of ∆G, this reaction is irreversible (just like reaction 1).
4-Catalytic breakdown of F1,6-BP into dihydroxyacetone phosphate (DHAP), a ketosis, and glyceraldehyde 3-phosphate (GAP), an aldose. The enzyme aldolase is responsible for this reversible aldol condensation.
5-Triose phosphate isomerase (TIM) is responsible for the interconversion of triose phosphate: DHAP and GAP, without additional energy input.
Energy recovery phase
1-GAP is oxidized by glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which catalyzes the transfer of a phosphate group to GAP to form 1,3-bisphosphoglycerate. In this reaction, two molecules of NAD + are reduced per molecule of glucose, and two molecules of inorganic phosphate are used.
Each NADH produced passes through the electron transport chain and 6 ATP molecules are synthesized by oxidative phosphorylation.
2-Phosphoglycerate kinase (PGK) transfers a phosphoryl group from 1,3-bisphosphoglycerate to ADP, forming two ATP and two 3-phosphoglycerate (3PG) molecules. This process is known as substrate-level phosphorylation.
The two ATP molecules consumed in the reactions of HK and PFK are replaced by PGK at this step in the pathway.
3-3PG is converted to 2PG by phosphoglycerate mutase (PGM), which catalyzes the displacement of the phosphoryl group between carbon 3 and 2 of glycerate in two reversible steps. The magnesium ion is also required by this enzyme.
4-A dehydration reaction catalyzed by enolase converts 2PG into phosphoenolpyruvate (PEP) in a reaction that does not require energy investment, but generates a compound with greater energy potential for the transfer of the phosphate group later.
5-Finally, pyruvate kinase (PYK) catalyzes the transfer of the phosphoryl group in PEP to an ADP molecule, with the concomitant production of pyruvate. Two molecules of ADP are used per molecule of glucose and 2 molecules of ATP are generated. PYK uses potassium and magnesium ions.
Thus, the total energy yield of glycolysis is 2 molecules of ATP for each molecule of glucose that enters the pathway. Under aerobic conditions, the complete degradation of glucose involves obtaining between 30 and 32 molecules of ATP.
Fate of glycolytic intermediates
After glycolysis, pyruvate undergoes decarboxylation, producing CO2 and donating the acetyl group to acetyl coenzyme A, which is also oxidized to CO2 in the Krebs cycle.
Electrons released during this oxidation are transported to oxygen through mitochondrial respiratory chain reactions, which ultimately drives ATP synthesis in this organelle.
During aerobic glycolysis, the excess pyruvate produced is processed by the enzyme lactate dehydrogenase, which forms lactate and regenerates part of the NAD + consumed steps up in glycolysis, but without the formation of new ATP molecules.
Lactate Dehydrogenase Mechanism (Source: Jazzlw via Wikimedia Commons)
In addition, pyruvate can be used in anabolic processes that lead to the formation of the amino acid alanine, for example, or it can also act as a skeleton for the synthesis of fatty acids.
Like pyruvate, the end product of glycolysis, many of the reaction intermediates serve other functions in catabolic or anabolic pathways important to the cell.
Such is the case of glucose 6-phosphate and the pentose phosphate pathway, where the ribose intermediates present in nucleic acids are obtained.
References
- Akram, M. (2013). Mini-review on Glycolysis and Cancer. J. Canc. Educ., 28, 454–457.
- Esen, E., & Long, F. (2014). Aerobic Glycolysis in Osteoblasts. Curr Osteoporos Rep, 12, 433–438.
- Haanstra, JR, González-Marcano, EB, Gualdrón-López, M., & Michels, PAM (2016). Biogenesis, maintenance and dynamics of glycosomes in trypanosomatid parasites. Biochimica et Biophysica Acta - Molecular Cell Research, 1863 (5), 1038–1048.
- Jones, W., & Bianchi, K. (2015). Aerobic glycolysis: beyond proliferation. Frontiers in Immunology, 6, 1–5.
- Kawai, S., Mukai, T., Mori, S., Mikami, B., & Murata, K. (2005). Hypothesis: structures, evolution, and ancestor of glucose kinases in the hexokinase family. Journal of Bioscience and Bioengineering, 99 (4), 320–330.
- Nelson, DL, & Cox, MM (2009). Lehninger Principles of Biochemistry. Omega Editions (5th ed.).