The Impact of Fermentation, Mitochondria and Regulation on Disease Treatment

Posted March 1, 2022 by beauty33

The Impact of Fermentation, Mitochondria and Regulation on Disease Treatment
Some cells only produce ATP through phosphorylation at the substrate level, either because they lack an electron transport chain or because they do not have a suitable terminal electron acceptor. They used glycolysis to generate 2 ATP and 2 pyruvate, and 2 NADH from a glucose molecule. However, these cells cannot continue glycolysis indefinitely, because when all available NAD+ has been reduced to NADH, they will quickly deplete NAD+. In respiratory cells, NADH transfers electrons to the electron transport chain and regenerates NAD+. In the absence of respiration, this method of regenerating NAD+ is not available.

The fermentation reaction reduces pyruvate and the electrons from NADH regenerate NAD+ (as opposed to pyruvate oxidation). These reactions produce ethanol in yeast and lactic acid in mammalian cells (hypoxic muscle cells and most tumor cells). The fermentation reaction takes place in the cytoplasm of prokaryotic and eukaryotic cells. In the absence of oxygen, pyruvate will not enter the mitochondria of eukaryotic cells.

Many (perhaps most) cancer cells have most of their energy from glycolysis and lactic acid fermentation, even if there is sufficient oxygen. Several explanations have been proposed. One is that cancer cells can promote biosynthesis and cell growth by not converting organic carbon into carbon dioxide, but using organic carbon to build cell biomolecules. Another hypothesis is that increasing glycolysis can allow tumor cells to outperform normal cells or immune system cells in terms of glucose. The third hypothesis is that the secretion of lactic acid leads to changes in the tumor cell environment, which is conducive to the growth and spread of tumor cells.

In nuclear cells, all metabolic pathways occur in the cytoplasm, except for chemical permeation and oxidative phosphorylation that occur on the plasma membrane. Prokaryotic cells can use alternative electron acceptors (such as nitrate and sulfate) for anaerobic respiration, although they prefer oxygen as the terminal electron acceptor to drive chemically permeable ATP synthesis. In the absence of any suitable electron acceptors, they use the fermentation route.

In eukaryotic cells, glycolysis and fermentation reactions occur in the cytoplasm. The rest of the pathway, starting with the oxidation of pyruvate, occurs in the mitochondria. Most eukaryotic mitochondria can only use oxygen as the terminal electron receptor for respiration. In the presence of oxygen, pyruvate enters the mitochondrial matrix and is oxidized to acetyl-CoA, which is then oxidized to CO2 through the citric acid cycle. The electron transport chain and ATP synthase are located on the inner mitochondrial membrane.

According to the endosymbiosis theory of mitochondrial origin, the position of the electron transport chain in the inner mitochondrial membrane and the pyruvate oxidation and citric acid cycle in the mitochondrial matrix are reasonable. These positions correspond to the plasma membrane and cytoplasm of the endosymbiont of aerobic bacteria, most likely a type of α-proteus, which is the ancestor of mitochondria. The outer mitochondrial membrane is derived from the endosomal membrane that initially engulfed the endosymbiont.

Further evidence supporting the endosymbiosis theory is that mitochondria have their own DNA in the form of circular chromosomes, which are topologically similar to bacterial chromosomes. The sequence of mitochondrial DNA is most similar to the gene sequence in α-proteobacteria. Mitochondrial ribosomes are more similar in structure to bacterial ribosomes than eukaryotic ribosomes. Mitochondria multiply in eukaryotic cells through fission, again similar to bacterial cell division.
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Last Updated March 1, 2022