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Biodynamic enzymology

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Biodynamic Enzymology enhances the central role of enzymes, the real workers from whose silent and tireless work depends the well-being of all cells and, when operating in an abnormal way, follows the trigger of reactive or degenerative processes capable of compromising the quality and/or duration of any organism. Intracellular reactions that take place in the cells are facilitated and therefore accelerated by enzymes. In all living systems, the purpose of the processes produced by enzymes is to reach the balance of an energy system that in this case affects the cells and then the referenced organs of the body. In fact, the enzymes allow the achievement of a given order (defined system enthalpy) that contrasts non-harmonious disorder when we speak of the contrary: entropy. To get an idea of how many enzymes are present in the human body, just think that about 80% of proteins present in the human body are enzymes.

Role of the enzymes and the first discoveries on their characteristics

The in-depth study of biology and branches connected to it is now focused on the use of predefined and well-established concepts. The same dogma of biology states that life starts from DNA and therefore does not take into account what's before. The DNA is in fact the product of a series of chemical reactions that happen thanks to the help of the enzymes. From this point of view, we should focus the study of the subject starting from the main elements of life: The Enzymes. Enzymes are biological catalysts that allow us to accelerate chemical reactions, or the speed with which they take place. They are proteinic macromolecules in which the structure is a depository of "memories", interactive with specific substrates. The initial study on enzymes assumed the active site of the enzyme as a rigid structure and the adaptation of a substrate in the active site more or less like a key in the lock. This first idea was suggested for the first time in 1894 by the German biochemist Emil Fischer,[1][2] In a model structured in this way, or according to the "key and lock" version, it was possible to guess how the enzymes were specific and coordinated between them. A more useful view of enzyme-substrate interaction derives from the model of induced adaptation.[3] This model assumes that the initial link of the substrate molecule to the active site will distort both the enzyme and the substrate, stabilizing the molecule of the latter in its transition state and thus making the link more susceptible to the catalytic attack.

The Quaternary Conformation of Proteins

The arrangements of proteins and protein sub-units in three-dimensional complexes constitutes the so-called quaternary structure; Integrations between sub-units are stabilized and driven by the same forces that stabilize the tertiary structure, which can be attributed to non-covalent multiple interactions. The first oligomeric protein to be subjected to X-ray analysis was the hemoglobin that contains four EME polypeptide chains, in which iron atoms are in ferrous state; The protein part, called globin, consists of two alfa chains (each of 141 aminoacidal residues) and from two beta chains (each of 146 aminoacidal residues). The way of wrapping and folding a polypeptide chain is long and obviously complicated and the principles that drive this process have not yet been identified in detail; Most proteins fall spontaneously in their right conformation, this behavior confirms that all data concerning the conformation must be contained in the same sequence of amino acids. One of the most important factors that govern the way to fold up a polypeptide lies in the distribution of its polar and non-polar aminoacids; While the protein is synthesized, its various hydrophobic aminoacids tend to be segregated within the molecule, at the same time all the polar aminoacids tend to dispose near the external portion of the protein molecule, where they are able to interact with the water and other polar groups.

The Importance of Enzymes in Diagnostic

Figure 1. Diagnostic with Enzymes

Because the measure of an enzymatic activity is useful for a clinical routine diagnosis the following conditions must be met.

1. The enzyme must be present in the blood, in the urine, or in other tissue fluids that can be easily found. Tissue biopsies should not be practiced as routine, but only in cases where the diagnostic value is particularly important.

2. The enzyme must be easily dosable and is even better if the method can be automated.

3. The quantitative differences between the enzymatic activities of normal and sick subjects must be significant, and there must be a good correlation between the levels of enzymatic activity and the pathological state.

4. It is also advisable that the enzyme is sufficiently stable to allow sample conservation at least for limited periods of time.

The serum is the fluid on which most analysis are done. Urine can only be used for few enzymes secreted by the kidneys. The enzymes in the serum can be divided into two categories:

  • specific plasma enzymes: for example, enzymes that carry out a plasma activity, such as enzymes involved in blood coagulation, in the activation of the complement, and in the metabolism of lipoproteins;
  • non-specific plasma enzymes: this category includes those enzymes that do not carry out physiological functions in the plasma for example enzymes inside the cells: amylase, lipase, phosphatase and other enzymes associated with cellular metabolism, whose presence in a normal serum in high quantity can be attributed to cellular suffering and/or tissue damage.

Several studies of Italian Scientist Ferorelli P. have determined and developed a new technique, by means of biodynamic components (substrates) obtained from the transformation of specific enzymes, that modulates all endogenous enzymes to organize reactions consistently with the principles of thermodynamics. In pathological conditions some tissue can be inflamed or about to reach necrosis. In several studies it's shown that act on metabolic pathways, by means of this biodynamic components, leads to improving of the cells and to coordinating of cellular metabolism, allowing to overcome the diseases.[4] Ideally, for diagnostic purposes, it would be desirable to analyze specific enzymes that would allow to identify the tissue from which they come; but unfortunately there exist isoenzymes that have a different distribution and they are aspecific in various tissues. The most studied case is that of the dehydrogenase lactate. The enzyme consists of four subunits. There are two types of subunits that, combining in various ways, give rise to five different forms of lactate dehydrogenase ɑ1ß, ɑ2ß, ß3, ɑß4, and ß5. These five forms, separable electrophoretically, are differently distributed in tissues (figure 1). In this way, although through the dosage of the activity of the dehydrogenase lactase present in the serum it is not possible to go back to the original tissue, the identification may be possible if the isoenzymatic distribution is determined by electrophoresis. Also for other enzymes in the serum we know multiple forms, such as alkaline phosphatase, amylase, creatine kinase, ceruloplasmin, 6-phosphate dehydrogenase glucose and aspartatransferase, but none of these isoenzymes was well characterized as the lactate dehydrogenase. Some of these isoenzymes can be identified with methods other than electrophoretic mobility, such as specificity (Figure 1). Today it is possible, in some cases, to distinguish the isoenzymes, make use of monoclonal antibodies. This method has been applied to recognize the different isoenzymes of human phospho fruttochinase, and to identify what was the absent form in the hereditary deficiencies of phospho fruttochinase. The isoenzymatic representations, in addition to give us indications on the origin of the tissue, are also useful in legal medicine. Since numerous enzymes of the serum and of the red blood cells are present in different isoenzimatic forms, the particular distribution in a blood sample can help to identify its origin. The isoenzymatic representations that are normally used by the Metropolitan Police Science Laboratory are those of adenosine deaminase, adenylated kinase, dehydrate carbonate, acid phosphatase, extrerasy, phospho-glucomutasi, aminopeptidase and lactilglutionione Liasi.

Complementary enzyme therapy

Complementary enzyme therapy concerns the set of treatments placed in support of traditional medical treatments for different types of pathologies, such as in the case of tumors, autoimmune diseases or chronic diseases such as Multiple Sclerosis. The use of biodynamic components favor cellular metabolic reactivation, obtaining excellent results.[5] The biodynamic components are able to maintain a cellular stability defined as "allostatic" during the pathological processes and are able to provide the energy necessary for intracellular support. In countries such as Germany or Austria which are commonly more accustomed to the use of biodynamic components to support many pathologies, it has been found that complementary enzymatic therapies can open new scenarios on the management of these pathologies, starting from biochemistry (and therefore from study of the cell) also arriving at the resolution of the pathology itself. For example, some researches about cardiovascular pathologies showed that the use of biodynamic components allowed the reduce of carotid plaques and a reduction of fatty liver and cholesterol levels,[6][7] Other researches showed how it's possible to improve the quality of life and increase body weight of patients in advanced lung cancer chemotherapy.[8] Usually, weight loss in patients with cancer is caused by cancer cachexia and chemotherapy-induced nausea and vomiting. These observations have been taken into consideration by Dr. Giuseppe Cotellessa, researcher and inventor of an original physical-mathematical procedure patented by ENEA on the basis of important practical applications beneficial for humanity. He mentioned about the potential action of biodynamic components on the regression of lung cancer and evaluation of the patient's quality of life.[9] Moreover, the effects of treatment with biodynamic components have also been studied from a metabolic point of view.[10] Data collected during the experiments, although preliminary, would suggest that the biodynamic components increases the performance of normal cells in the body, improving the quality of life of the patient. On the contrary, their activity would cause the reduction of energy in cancer cells slowing down the disease progression. It could deduce that these new technologies could help the treatment of cancer patients, obviously not as an antitumor drug, but as useful strategy to improve the quality of life by reducing the adverse symptoms of chemotherapy.

Bibliography

  • (IT) Nicholas C. Price, Lewis Stevens, Principi di enzimologia, Antonio Delfino Editore, 1996, ISBN 887287100X.
  • (IT) Fernando Mazzucato, Andrea Giovagnoni, Manuale di tecnica, metodologia e anatomia radiografica tradizionali, Piccin, 2018.

References

  1. Lemieux RU, Spohr U. How Emil Fischer was led to the lock and key concept for enzyme specificity. Adv Carbohydr Chem Biochem. 1994;50:1-20. (https://www.sciencedirect.com/science/article/abs/pii/S0065231808601493?via%3Dihub)
  2. Arieh Ben-Naim, The lock and key model for Molecular Recognition. Is it time for a paradigm shift? physics.bio-ph. 2018
  3. Jacques Monod. The phenomenon of enzymatic adaptation and its bearings on problems of genetics and cellular differentiation. Elsevier, 2 dic 2012 (https://books.google.it/books?hl=it&lr=&id=TchQ6gPzO_4C&oi=fnd&pg=PA68&dq=enzyme+model+of+induced+adaptation&ots=omxWjmrJgN&sig=-UAOAKmoHFIOFUpAA6R0p1XkdKs#v=onepage&q=enzyme%20model%20of%20induced%20adaptation&f=false)
  4. Ferorelli Pasquale, Antonelli Francesco, Shevchenko Anna, Doepp Manfred, Lenzi Stefano, Beninati Simone, Beneficial Effects of Oral Administration of a Nutritional Supplement in Asymptomatic and Symptomatic COVID-19 Patients, Journal of Food and Nutrition Sciences.
  5. Torricelli Piera, Antonelli Francesco, Ferorelli Pasquale, De Martino Angelo, Shevchenko Anna, Beninati Simone, Multiple Sclerosis: Effect of Oral Administration of an Antioxidant Dietary Supplement in C57BL6/N Induced Model of Experimental Autoimmune Encephalomyelitis, American Journal of Clinical and Experimental Medicine.
  6. Torricelli Piera, Ferorelli Pasquale, De Martino Angelo, Antonelli Francesco, Shevchenko Anna, Beninati Simone, Regression of Carotid Plaques in Individuals at Low-to-intermediate Cardiovascular Risk Treated with Citozym and Propulzym, European Journal of Preventive Medicine.
  7. Torricelli P., Ferorelli P., De Martino A., Antonelli F., Beninati S., The Influence of Preventive Multiple Micronutrients Supplementation on Liver Steatosis in High-cholesterol Fed C57BL6/N Mice, American Journal of Life Sciences.
  8. Torricelli P, Antonelli F, Ferorelli P, et al. Oral nutritional supplement prevents weight loss and reduces side effects in patients in advanced lung cancer chemotherapy.
  9. https://genioitalianogiuseppecotellessa.blogspot.com/2020/11/texidrofolico-sulla-regressione-del.html
  10. Antonelli Francesco, Ferorelli Pasquale, De Martino Angelo, Borromeo Ilaria, Shevchenko Anna, Beninati Simone, Effect of a Novel Dietary Supplement on Cancer Cells Metabolism, International Journal of Tumor Therapy, Vol. 8 No. 1, 2019, pp. 10-15. doi: 10.5923/j.ijtt.20190801.03



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