PROTEINS AND ENZYMES REJECT COINCIDENCE

Prof. Dr. Ömer İrfan KÜFREVİOĞLU
Atatürk University,Faculty of Science, Chemistry Department, Biochemistry,Erzurum
[email protected]

Perfect Organization among the Biomolecules in Living Beings

Although millions of living beings consume oxygen and millions produce it, the oxygen content in the atmosphere has been maintained at 21% for thousands of years. These scientific facts are great evidences for the existence of Allah, who creates and governs all living creatures on earth with His infinite power and knowledge.

Biomolecules in living beings are very diverse and have a complex structure. For example, the Escherichia coli bacterium, on which biochemists work most and whose biochemical properties are elucidated most, has about 7,000 kinds of compounds. About 4,000 of those compounds in this bacterium, which  can be seen under the microscope only after it is magnified tens of thousands of times and which has a weight of 500 billionth of a gram, are proteins and more than three thousand of them are nucleic acids. Thousands of complex organic compounds in this bacterial structure are synthesized from water, ammonia and glucose molecules: A skill that a chemist cannot imagine is displayed here. If a chemist were asked to synthesize an amino acid and a lipid in a single vessel using the same starting materials, he would not accept it at all because only one reaction can be carried out in a single vessel; and the synthesis he is asked to make from the starting materials mentioned above is possible with more than one hundred reactions. However, if we suppose that the E.coli cell is a vessel, approximately 7000 kinds of organic compounds are made from simple water, ammonia and glucose in 20 minutes and the cell is divided. [1]

There is an excellent circulation among biomolecules in the living sphere called the biosphere. Nitrogen, which is present in the structure of proteins and nucleic acids, is an important element transferred among living beings. Although the nitrogen molecule (N2) is very abundant in the atmosphere, it does not react easily due to the triple covalent bond between two nitrogen atoms. In nitrogen fixation bacteria,nitrogen is converted to ammonia (NH3) by using ATP (energy source). Soil microorganisms then oxidize NH3 to NO^-2(nitrite) and to NO^-3(nitrate). Plants absorb nitrogen from soil in the form of NO^-3and reduce it to NH3, amino acids and other compounds. After they are used by animals, they are released again to the soil in reduced form. These incidents are called nitrogen cycle (Figure 1).

The parameters such as the number, variety and lifespan of bacteria, plants, animals and humans that function in the nitrogen cycle should be kept under constant control so that nitrogen can always be kept at 78% in the air.

The parameters such as the number, variety and life of bacteria, plants, animals and humans that function in the nitrogen cycle should be kept under constant control so that nitrogen is always kept at 78% in the air.

The same thing applies to oxygen. Although millions of living beings consume oxygen and millions produce it, the oxygen content in the atmosphere has been maintained at 21% for thousands of years. These scientific facts are great evidences for the existence of Allah, who creates and governs all living creatures on earth with His infinite power and knowledge.

Figure 1. Nitrogen Cycle in the realm of living beings.

Acceleration of Reactions by Enzymes

One million carbon dioxide molecules bind to the active site of the carbonic anhydrase enzyme in one second and they are converted to bicarbonate.

Reactions in living beingsaccelerate at least one hundred million times with enzymes. Catalysis of all chemical reactions in biological systems is carried out with molecules called enzymes. Some of these reactions are very simple, such as the combination of CO2 with H2O, and some are extremely complex, such as the replication of an entire chromosome. Enzymes have a remarkable catalytic power. Today, more than 2000 enzymes have been identified; all of them are proteinsexcept for some catalytic RNA molecules.

Enzymes are catalysts that are used to accelerate chemical reactions in living organisms. No byproducts are allowed to occur at that time. Thus, 100% product yield is achieved in the system.

Carbonic anhydrase is one of the enzymes with the highest catalytic power (1,000,000 s^-1). That is, the;

Synthesis or degradation reactions that cannot be carried out under normal laboratory conditions by chemical scientists occur in living beings without any by-product. In other words, it is understood that the enzymes are the officers of a being who has infinite knowledge, will and power working based on His plan and program.

reaction on a carbonic anhydrase molecule (Figure 2) occurs in 1/1.000.000 seconds, that is,1 microsecond. It means one million carbon dioxide molecules bind to the active site of the carbonic anhydrase enzyme in one second and they are converted to bicarbonate. It is observed in the studies carried out on other enzymes that the reactions accelerate10⁸ to 10²⁰ times in the presence of enzymes.

Thus, reactions carried out under very high temperature and very high pressure occur under normal intracellular conditions and atmospheric pressure. In addition, enzymes are highly specific to both the types of reactions they catalyze and the substrates they convert into products. They usually catalyze a single chemical reaction or similar reactions of the same type. Thus, synthesis or degradation reactions that cannot be carried out under normal laboratory conditions by chemical scientists occur in living beings without any by-product. In other words, it is understood that the enzymes are the officers of a being who has infinite knowledge, will and power,working based on his plan and program.

Figure 2. Three dimensional (tertiary) structure of human carbonic anhydrase II enzyme. [2]

Protein Synthesis (Translation)  Occurs in Seconds

Proteins are the most important compounds of all living beings and the most abundant compounds of cells. They have hundreds of vital functions such as enzymatic catalysis, transport of small molecules and ions in blood and their storage in tissues, mechanical movement, mechanical support, and the formation of the body's defense system by entering the antibody structure.

Proteins acquire primary structure when amino acids are attachedby peptide bond in ribosomes. Subsequently, after the secondary structure formed by hydrogen bonds, they acquire tertiary structure, and, in some proteins, a three-dimensional structure called quaternary. Thus, they have the structure to function biologically. [3]

Figure 2 shows the tertiary structure of human carbonic anhydrase II as an example.

A protein acquires primary structure in biological factories with supramolecular structure, which are called ribosomes and which consist of proteins and RNAs, in the cell. It has been determined that An E.coli cell has approximately 20 thousand ribosomes and a growing mammalian cell has about 10 million ribosomes. A protein synthesis of 100 amino acids occurs in about 5 seconds in an E. coli cell. However, when we explain the subject of protein synthesis in a lesson, the narration of the incidents that occur during the coupling of two amino acids sometimes takes tens of hours. Hundreds of kinds of macromolecules work in coordination for this work. Among these macromolecules are ribosomes consisting of a complex of RNA and a large number of proteins, as well as enzymes activating tRNAs, dissolved protein synthesis factors and mRNA in the protein structure.

Let us also express a fact that there is no place for chance during protein synthesis: Amino acids do not move freely in the cell very much. Since they will be used in protein synthesis, almost all [amino acyl-tRNA + GTP + EF-Tu) (elongation factor)] are in the form of triple complexes. They try to match the mRNA codon in the A region of the ribosome by coming to this region through diffusion to bind with the anticodons of 20 kinds of triple complex tRNAs that bring amino acids. Considering that 18 amino acids are added to the chain in one second and 20 kinds of triple complexes are tried, it is understood that 18x20 trials are performed per second. If they carry the appropriate anticodon, matching is performed. Therefore, a time period long enough for the triple complex to try the anticodon is necessary. The longer the time, the more likely the synthesis of the appropriate proteins. Indeed, the correct protein synthesis is set here at the rate required by the cell. [4]

Protein Folding cannot Occur by Chance According to Probability Theory

Polypeptide chains are formed as amino acids are aligned side by side like rosary beads. However, they need to be folded in order to have secondary and then tertiary structure to function. For, when proteins are synthesized, they are alone and when they do not have disulfide binding; they have a primary structure. How long will such a trial and search take according to the probability theory?

Let us consider a small protein containing 100 amino acids. Assuming that each amino acid will have 3 different conformation (sequence in space), the total number of structures of the protein will be 3¹⁰⁰, i.e. 5x10⁴⁷. Assuming that the transition from one structure to another takes 10^-13 seconds, the total search time will be 5x10³⁴ seconds, i.e. 1.6x10²⁷ years. If it is considered that the number of conformation of an amino acid is more than three and that the transition of the protein structure from one shape to another will take longer than 10^-13 seconds,  it is evident that this figure is calculated very low.

It has been understood in recent years that some proteins called heat shock proteins (hsp) or 'chaperons' have the duty of preventing misfolding. [5]

Thousands of proteins are synthesized in each cell at any time and they are folded to have the optimal structure to function perfectly. Sane people who think objectively reject the view that protein foldingcan happen by chance.

The Wonder in the Occurrence of Organs

It is possible for each organ to occur in any part of the body but they are created in certain places, which is an evidence that it is the work of an infinite power, will and wisdom.

There are about 100 trillion cells in man; and each cell contains 2 meters of DNA except for mature erythrocyte cells. There are approximately 23,000 protein genes on each DNA existing in each cell. Genes are assigned to determine the types of proteins made by cells.

The flow of genetic information in normal cells are as follows:

However, each gene is expressed, that is opened, in certain cells and at certain times according to the needs of the organism, For instance, the albumin gene is opened only in the liver; the globin gene is opened in reticulocytes, which are the initial forms of red blood cells. In human beings, every cell, except for the red blood cell, contains 23,000 protein genes, but each gene is opened in different cells and according to need. Thus, it is possible for each of our organs tooccur in any part of the body but they are created in certain places, which doubtlessly shows that it is the work of an infinite power and will.

The most important step in the transformation of genetic information in eukaryotes and prokaryotes into proteins, that is, the control and regulation of genetic expression, is the initial stage of transcription. Cells do not need every protein evenly. Some metabolic pathways need to be accelerated and others to be slowed down as a result of the conditions in which the nutrient medium is present, the signals received from outside and especially the function and structure differences of each cell in multicellular cells. To do this, the synthesis of proteins and enzymes involved therein must be suppressed or activated. This mechanism of regulation of transcription, some examples of which are explained by the "operon" model in prokaryotes, is a much more complex and multifactorial incident in multicellular eukaryotes. In fact, a gene construction also includes "transcription elements (TE)" that regulate transcription. Promoters are sequences on DNA that bind to RNA polymerases and determine the starting point of transcription; transcription elements are the arrays on DNA that regulate the rate of transcription by binding various proteins called transcription factors (TF). One or more of the hundreds of different types of transcription factors, which are different in structure and activated in different ways, bind to these regions. They are assigned to regulate eukaryotic genetic expression. [6]

A New Living Being Does Not Come Into Being With Mutation

It is unthinkable that one species can come into being by chance through mutations from another species. Changes in the base sequence of genes are called mutations. Most of the sudden changes (mutations) in genes are lethal.It is not possible to attribute the formation of new species to mutation.For instance, changing only one of the hundreds of bases in the globin gene causes the structure of the red blood cell to change, leading to sickle cell anemia:

There are 4 million base pairs in the E. coli genome while there are 3.2 billion base pairs in man. According to the view that human beings evolved from bacterial cells, after a bacterium with approximately 4 million base pairs evolved by chance and formed different living things, it was transformed into man with 3.2 billion base pairs, which is impossible to explain according to the probability theory.

The issue is explained as follows in the book called İşaratü’l İ’caz:

“It has also been demonstrated by biology and botany that there are more than two hundred thousand sorts of species and that each has a progenitor and forefather. Contingency and createdness prove therefore that necessarily these progenitors and forefathers emerged without intermediary from the hand of divine power. Moreover, causes cannot be imagined at the first creation as they are imagined in the chains of causes. Furthermore, the delusion of the splitting off of some species from others is invalid, for since either the offspring are barren or the line becomes extinct, an intervening species mostly does not become the start of new chains through reproduction.

It is most likely therefore that since the origins and beginnings are thus, the successive members will also be thus”.

Accordingly, every living species has a first ancestor, which was created without any means, that is, without any reason. Since researches are conducted based on reasons in positive sciences, the first creation is tried to be explained based on reasons and no answer to satisfy the hearts and minds has been found. However, when the issue is viewed from the window of the Quran, it is understood that the first ancestor of every species including Hz. Adam was created bydivine power without any means and that the species were derived from them.

In conclusion, the duty of the catalysis of all metabolic incidents in living beings are assigned to enzymes. Reactions with enzymes occur 10⁸ to 10²⁰ times faster. For instance, the carbonic anhydrase enzyme causes one million carbon dioxide to be converted to bicarbonate per second. Proteins are produced rapidly in ribosomes and then are quickly provided with the most appropriate conformation. When these incidents are examined based on probability theory,they show that chance has no place whatsoever.

With the excellent organization of the biomolecules in the cells, each cell works according to the principles of maximum economy;more or fewer substances than necessary are not produced. There are about 100 trillion cells in human beings;each cell, except for mature erythrocyte, contains 2 meters of DNA. There are approximately 23 thousand protein genes on each DNA existing in each cell. However, each gene is expressed in specific cells and at certain times.

All these incidents take place perfectly and in unity, which proves that there is no coincidence/chance in the universe, that everything is the work of Allah, who has infinite knowledge, will and power, and that it is impossible to come across with coincidence in the universe.

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[1] Lehninger, A.L., Biochemie (übersetztvon H. Kleinigund B. Liedvogel), Weinheim, VerlagChemie, 2.Auflage, 1983.
[2] KILIÇ, D. İnsan Karbonik Anhidraz II (hCAII) Geninin Klonlanması, E. Coli ’de Ekspresyonu, Karakterizasyonu, Yönlendirilmiş Mutagenez İle Mutant hCA II Genlerinin Eldesi ve Mutant Proteinlerin İnhibitörlere Karşı İlgisinin Araştırılması, Atatürk Üniversitesi Fen Bilimleri Enstitüsü, Kimya Anabilim Dalı, Doktora Tezi,  2017.
[3] Stryer, L., Biochemistry, New York, W.H. Freeman and Company, 3rdedition, 1988.
[4] Keha ve Küfrevioğlu, ibid.
[5] Nelson D.L., Cox, M.M., (Çeviri editörü: Prof. Dr. Necdet KILIÇ), 2005, Lehninger Biyokimyanın İlkeleri. PalmeYayıları: 313, Palme Yayın, Dağıtım, Pazarlama, İç ve Dış Ticaret  Ltd. Şti. Ankara. pp 193-194.
[6] Lehninger, A.L., Nelson, D.L., Cox, M.M. , 1993, Keha ve Küfrevioğlu, 2012.
[7] Nursi, Badiuzzaman, S. İşârâtü’lİ’câz. p. 416.