2022-05-06 21:00:00
A difficult lesson that scientists studying the biology of molecules must learn is that the same molecule can perform multiple functions in different types of cells. It is true, fortunately not all the molecules of life lead double or triple lives, and most tend to collect themselves at home, with their molecular husband or wife, and do not pose too complicated problems for researchers to find out what life they lead. Others, however, multiply their activities and can be found stimulating various types of cancers, affecting embryonic development or influencing the progress of Alzheimer’s disease, among other interesting activities. These are complicated molecules to tame, and more difficult to understand, but they are the most interesting and the ones that arouse scientific controversy. One of these molecules, which is receiving a recent increase in research attention, is the enzyme called phosphoglycerate dehydrogenase.
The enzyme phosphoglycerate dehydrogenase is an important enzyme in the metabolism of glucose and also in that of the amino acid serine, one of the twenty amino acids necessary for the manufacture of all proteins in our body. The situation of this enzyme at a crossroads of metabolic pathways that links carbohydrates and proteins makes it an important metabolic regulation point. The activity of this enzyme is regulated by the amount of serine available in the cell, since this amino acid can also be incorporated with the diet, in which case the cell does not need to invest resources in its production, and it is inhibited. The activity of the enzyme, however, and also the amount produced, can increase under certain circumstances, for example when the cell needs to reproduce, which happens in the case of uncontrolled cell division that is cancer.
In relation to the latter, recent research, published in the last two years, indicates that the production of the phosphoglycerate dehydrogenase enzyme is increased in various types of cancer, among which we can mention thyroid, pancreatic and breast cancer. The levels of its functioning and the amount of enzyme produced in these tumors are associated with their aggressiveness, with the most aggressive tumors being those that produce the most phosphoglycerate dehydrogenase.
The amount of phosphoglycerate dehydrogenase produced has also been associated with the resistance of hepatic carcinoma tumor cells to an antitumor drug called Sorafenib. This drug is an inhibitor of certain intracellular signals that lead to uncontrolled cell growth and therefore promote tumor growth. Sorafenib blocks those signals and slows down tumor growth. However, some tumor cells adapt to the presence of Sorafenib, mutate and develop resistance to the activity of this antitumor drug. It has been proven that the most resistant cells are the ones that produce the most phosphoglycerate dehydrogenase enzyme. The activity of this enzyme has been confirmed as responsible for resistance, since treatment with another drug that inhibits its activity, that is, it blocks the functioning of the phosphoglycerate dehydrogenase enzyme, makes tumor cells sensitive to Sorafenib again. Thus, treatment with Sorafenib and the phosphoglycerate dehydrogenase inhibitor has been revealed as a more effective antitumor therapy. So far a summary of the importance of the enzyme phosphoglycerate dehydrogenase in cancer.
In 2020, a study, carried out by a large group of French and Swiss researchers, published in the prestigious Cell Metabolism journal, established a relationship between the progression of Alzheimer’s disease and the state of serine metabolism in astrocytes, brain cells that support neurons and also perform important functions in the control of blood flow in the brain. The study was carried out stimulated by previous observations indicating that glucose metabolism was affected in Alzheimer’s patients. Since the metabolism of glucose and that of serine are related, as we have said, the researchers decided to study what the situation of Alzheimer’s patients was in relation to the production of serine in their brains. Studies indicated that serine production was lower than normal in astrocytes from Alzheimer’s patients and in laboratory animals used for research with Alzheimer’s disease. The abnormality also extended to all aspects of brain biology in which the amino acid serine was involved. In particular, the deficiency in the production of serine affected the plasticity of the synapses, that is, their reorganization capacity, a process absolutely necessary for learning and memory. The authors therefore recommended the use of serine dietary supplements to try to slow the progression of the disease.
This reduced production of serine suggested that the enzyme phosphoglycerate dehydrogenase would not be produced at normal levels in the brains of Alzheimer’s patients. On May 3, 2022, researchers from the University of San Diego, in California, published, also in the journal Cell Metabolism, the results of a study aimed precisely at determining the production levels of this enzyme in the brains of Alzheimer’s patients. The results of the study indicated that the production of the enzyme phosphoglycerate dehydrogenase was increased, not decreased, in the brains of Alzheimer’s patients analyzed after death. The brains of those who had died without showing symptoms of this disease showed lower levels of phosphoglycerate dehydrogenase production than those who had died after showing symptoms. The more severe the symptoms, the higher the production levels of this enzyme. The researchers have also confirmed that this relationship between the amount of phosphoglycerate dehydrogenase and the progression of Alzheimer’s disease is maintained in strains of laboratory mice suffering from this disease.
This is how things are now. These studies open up a scientific controversy about the advisability or not of consuming serine supplements as a means to stop Alzheimer’s disease. The results of the French study two years ago seem to advise its consumption, while the results of the American study seem to advise against it, since the amount of enzyme phosphoglycerate dehydrogenase, increasing during the progress of the disease, seems to indicate that the amount of serine produced It should be higher, not lower than normal.
We will have to wait for new studies to elucidate what happens, but without knowing the cause that really pushes the increase in the production of phosphoglycerate dehydrogenase in the brains of Alzheimer’s patients, we will not be able, in my opinion, to reach a satisfactory answer. And it is possible that both an increase in the production of phosphoglycerate dehydrogenase and a decrease in the production of serine are both compatible facts. It is possible that some problem in the production of serine is the reason for the increase in the production of phosphoglycerate dehydrogenase, in an attempt by the cells to compensate for the serine deficit, and that both facts, apparently contradictory, nevertheless reflect a cause deeper that would explain both at the same time. That cause may be yet to be revealed, but it is what I think could help to better understand the generation and development of the terrible neurodegenerative disease that is Alzheimer’s disease.
(Jorge Laborda 05/06/2022)
Works by Jorge Laborda.
Your defenses against coronavirus
Your defenses against coronavirus
Deflamed immunology: An introduction to the immune system and its pathologies
Deflamed immunology: An introduction to the immune system and its pathologies
Deflamed immunology: An introduction to the immune system and its pathologies
Kilo of Science Volume XII eBook
Kilo of Science Volume XII Paper
Kilo of Science Volume I. Jorge Laborda
Kilo of Science Volume II. Jorge Laborda
Kilo of Science Volume III. Jorge Laborda
Kilo of Science Volume IV. Jorge Laborda
Kilo of Science Volume V. Jorge Laborda
Kilo of Science Volume VI. Jorge Laborda
Kilo of Science Volume VII. Jorge Laborda
Kilo of Science Volume VIII. Jorge Laborda
Kilo of Science Volume IX. Jorge Laborda
Kilo of Science Volume X. Jorge Laborda
Kilo of Science Volume XI. Jorge Laborda
Matrix of homeopathy
Chained circumstances. Ed.Lulu
Chained circumstances. Amazon
One moon, one civilization. Why the Moon tells us that we are alone in the Universe
One moon, one civilization. Why the Moon tells us that we are alone in the Universe
One Moon one civilization why the Moon tells us we are alone in the universe
The thousand and one bases of ADN and other science stories
Adenius Fidelius
The intelligence funnel and other essays
The gods have been cloned
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