Biology:Enzymatical processes

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Enzymatical processes topic wants to enhance the central role of enzymes, the real workers from whose silent and tireless work depends the well-being of all cells in fact, intra-cellular reactions that take place in the cells are facilitated and therefore accelerated by enzymes.

Role of the enzymes and the first discoveries on their characteristics

Enzymes are biological catalysts that allow to accelerate chemical reactions, or the speed with which they take place. 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 Importance of Enzymes in Diagnostic

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.
Figure 1. Diagnostic with Enzymes

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 it 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). 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 phosphofructokinase. 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.

Enzymes in therapy

Thanks to the progresses in the field of the research have provided the bases for the development of new "enzymatic drugs", in fact, it's known the many enzyme substrates can be used in support of traditional medical treatments for different types of pathologies.[4][5] The use of biodynamic components favor cellular metabolic reactivation, obtaining excellent results, because they 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.[6] The discoveries and furtherance with which the therapeutic enzymes are being produced have led to new opportunities and prompted new open doors in the field of medication for both therapeutic and analytical purposes.[7] It has been found that 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.[8] For example, some researches showed how it's possible to improve the quality of life of patients and nowadays many laboratories are evaluating the current discoveries and advancements in therapeutic enzymes to provide a scope of improvement for the existing enzymes and help overcome the challenges to further develop new ones.[9] 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.[10]

Enzymes in Agriculture

With the high use of pesticides and herbicides, both the soil and the plants are deprived of enzymes capable of working organic matter. This leads to the depletion of the soil, nutrients and an increase in infections. Following these observation European Union (EU) has issued a new legislation and the Italian Senate, on 20th May 2021, approved a draft law "Ddl 988" about Provisions for the protection, development and competitiveness of agricultural, agri-food and aquaculture production using biological methods. The latter would allow to work with enzymes in agriculture, enriching the soil with vital nutrients for plants and obtain all the substances necessary to overcome adversity. Thanks to enzymological studies in agricolture it's possible to renew the soil by means of natural processes that characterize all living organisms and ecological systems. From the reseaches are well known the advantage of the crop rotation because it allows to the enzymes to settle in the soil and periodically enrich it guaranteeing resistance to parasites for cultivated plants.[11]

References

  1. ↑ Lemieux, Raymond U.; Spohr, Ulrike (1994). "How Emil Fischer was Led to the Lock and Key Concept for Enzyme Specificity". Advances in Carbohydrate Chemistry and Biochemistry 50: 1–20. doi:10.1016/S0065-2318(08)60149-3. PMID 7942253. 
  2. ↑ Ben-Naim, Arieh (2018). The lock and key model for Molecular Recognition. Is it time for a paradigm shift?. 
  3. ↑ Monod, Jacques (2 December 2012). "The phenomenon of enzymatic adaptation and its bearings on problems of genetics and cellular differentiation". in Ullmann, Agnes. Selected Papers in Molecular Biology by Jacques Monod. Elsevier. pp. 68–134. ISBN 978-0-323-14263-2. https://books.google.com/books?id=TchQ6gPzO_4C&pg=PA68. 
  4. ↑ Kunamneni, Adinarayana; Ogaugwu, Christian; Goli, Diwakar (2018). "Enzymes as therapeutic agents". Enzymes in Human and Animal Nutrition. pp. 301–312. doi:10.1016/B978-0-12-805419-2.00015-0. ISBN 978-0-12-805419-2. 
  5. ↑ Baldo, Brian A. (February 2015). "Enzymes Approved for Human Therapy: Indications, Mechanisms and Adverse Effects". BioDrugs 29 (1): 31–55. doi:10.1007/s40259-015-0116-7. PMID 25648140. 
  6. ↑ Torricelli, Piera; Antonelli, Francesco; Ferorelli, Pasquale; Borromeo, Ilaria; Shevchenko, Anna; Lenzi, Stefano; De Martino, Angelo (March 2020). "Oral nutritional supplement prevents weight loss and reduces side effects in patients in advanced lung cancer chemotherapy". Amino Acids 52 (3): 445–451. doi:10.1007/s00726-020-02822-7. PMID 32034492. 
  7. ↑ Tandon, Siddhi; Sharma, Anjali; Singh, Shikha; Sharma, Sumit; Sarma, Saurabh Jyoti (June 2021). "Therapeutic enzymes: Discoveries, production and applications". Journal of Drug Delivery Science and Technology 63: 102455. doi:10.1016/j.jddst.2021.102455. 
  8. ↑ Ferorelli, Pasquale; Antonelli, Francesco; Shevchenko, Anna; Mischiati, Carlo; Doepp, Manfred; Lenzi, Stefano; Borromeo, Ilaria; Feriotto, Giordana et al. (20 July 2021). "Reduction in Fatigue Symptoms Following the Administration of Nutritional Supplements in Patients with Multiple Sclerosis". Medical Sciences 9 (3): 52. doi:10.3390/medsci9030052. PMID 34287336. 
  9. ↑ Pleszczyńska, Małgorzata; Wiater, Adrian; Bachanek, Teresa; Szczodrak, Janusz (May 2017). "Enzymes in therapy of biofilm-related oral diseases: Enzymes in Therapy of Oral Diseases". Biotechnology and Applied Biochemistry 64 (3): 337–346. doi:10.1002/bab.1490. PMID 26969579. 
  10. ↑ Mohamed, Mona Mostafa; Sloane, Bonnie F. (October 2006). "Cysteine Cathepsins: Multifunctional Enzymes in Cancer". Nature Reviews Cancer 6 (10): 764–775. doi:10.1038/nrc1949. PMID 16990854. 
  11. ↑ Singh, Geeta; Bhattacharyya, Ranjan; Das, T.K.; Sharma, A.R.; Ghosh, Avijit; Das, Shrila; Jha, Pramod (1 December 2018). "Crop rotation and residue management effects on soil enzyme activities, glomalin and aggregate stability under zero tillage in the Indo-Gangetic Plains". Soil and Tillage Research 184: 291–300. doi:10.1016/j.still.2018.08.006. https://www.sciencedirect.com/science/article/pii/S0167198718309103. 

Further reading




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