THE PHYSIOLOGICAL TIME

 by Ciprian-Gabriel Chisega

 What time is ? Is a common question. But, now I don't reffering to how hours and minutes your wristwatch is showing. I want talk about more than that. Time have a very strong bond with our body, and our cells. Yes, cells are very complicated chemical mechanisms, but, on the other hand, they are also very delicated time measuring mechanisms. They are amaizing chemical units. After all, they are also living organisms.

On Earth we have two kinds of living cells : prokaryotic (common in bacteria) with a circular DNA shape, and eukaryotic cells (in other regnums, including humans) with a double hecical structure.

 For time understanding, we must understand better the functioning of cell, and that any  process developped inside is very vell controlled by a mix of proteins, enzymes, hormons, growing factors, CDKs (cycline dependent kinases), etc.

 In the text below I insist about cell description, because I think that is an important step to control the time.

 Prepared for action ? Go !

 Eukaryotic cells has highly organised structure with compartments and cell organelles, whose functions can be highly specialized. However, all these structures are composed of few classes of macromolecules : proteins, carbohydrates, nucleic acids and membrane forming lipids. Undoudty, proteins are the key players here. Proteins form the structures of cell acting as well as building blocks as assembly factors or other macromolecules. They also act as enzymes that catalyse both the anabolic and catabolic reactions in the cell.

What are these proteins ? They are linear arrays of 20 different kinds of aminoacids : glycine (Gly), alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), phenil alanine (Phe), cysteine (Cys), methionine (Met), aspartic acid (Asp), Aspargine (Asn), glutamic acid (Glu), glutamine (Gln), lysine (Lys), arginine (Arg), proline (Pro), histidine (His), triptophane (Trp), serine (Ser), threonine (Thr), tyrosine (Tyr). It is the aminoacid sequence that fundamentally determines the three-dimensional structure of protein and therefore - its properties. However, proteins lack two key features that are needed for living organisms : they can not replicate and because they can not replicate, they are unable to maintain the genetic information for a long time.

In all living cells, not only in eukaryotes, the genetic information is stored in the base sequence of DNA. When a new protein is needed, the base sequence of DNA encoding is translated to the aminoacid sequence. DNA fulfills also the second demand. Because of its double helical structure, it is easily replicated, when original strand can be copied using the other, complementary strand as a template in eukaryotic cells the DNA is packed in the nucleus of the cell.

For a living organism, it is crucially important, that its genomic integrity is faithfully maintained and that its genome is carefully replicated during proliferation. To allow this cell must have proper machineries for DNA replication, for DNA replication, for DNA repair and recombination, as well for cell cycle control.

The DNA replication process needs :

the presence of DNA template;-        

the presence of four desoxiribonucleosid triphosphates (dATP - d adenosinetriphosphate, dGTP -d guanosinetriphosphate, dCTP - d cytosinetriphosphate and dTTP - d thyminetriphosphate)

the presence of magnesium ions;

a complex enzymatical system which contains :

a)       helicase - an enzyme which unbinbs the parental duplex with two complementar strands display, allowing nucleotides sequence reading by the replication enzymes. The parental duplex unbinding is a step by step proces, on separate small pieces of DNA, in the same time the replication advances. The two strands remain separate due to of  the DNA stabilisation proteins intervention, which bind it firmly;

b)       topoisomerases - which solves topological poblems that can apear in parental duplex unbinbing;

c)       DNA primase - an enzyme that synthesises small RNA fragments (primers) for DNA synthesis initiation;

d)       DNA polymerases, DNA dependent - important in DNA daughter strand replication process. Until today there are known six different mammalian polymerases with specified functions in replication process;

e)       DNA ligase - an enzyme that binds DNA fragments produced in replication proces.

In adult organisms some cells are terminally differentiated, which means that either they have completely stopped dividing or if they are stil able to divide they can produce only copies of themselves, ie clones. If the cells have maintained the potential to divide there must be a strict control to regulate this process. Something must induce that proliferation and also stop it when needed. It was found out that this control has failed in cancer. To regulate development it is important that the cycle length of the cell is correct and cells will exit the division cycle when they have reached the final stage of their developmental pathway.

The eukaryotic cell cycle has four distinct periods : during S-phase (S for synthesis) the whole genome (that is all nuclear DNA) is replicated, during M-phase (M for mitosis) daughter cromosomes are segregated between the poles of the cell and finally the contractile ring seals the membranes between the daughter genomes n process called cytokinesis ie the cell divides. The periods between mitosis and S-phase are called G1 and G2 phases (G for gap). It is crucially necessary that the DNA is replicated completely, once and only once during one division cycle.

Let's take a look in S-phase!

1.        Helicase - unbinds the parental duplex separating the two DNA strands step by step;

2.        On one strand the replication is continuous, and on another strand it works discontinuously. The polymerase needs primers for binding;

3.        It is a third enzyme - primase - that will manufacture these primers. After that the polymerase will fill the spaces between primers with nuclear bases. After the spaces are filled polymerase will eliminate the anterior used primers, and will the remained spaces with nuclear bases.

4.        But, at the STRAND END IT REMAINS A FRAGMENT THAT WASN'T COPIED, because a PRIMER DOESEN'T EXIST.

5.        This way, after each replication the cell will lose some of its nuclear information, and when the information is not sufficient for survival, the cell will die.

CONCLUSION

                The time has an organical nature. We, all the living beings, are temporal organisms, because all our cels have an temporal mechanism included. Because the time is so deep introduced in our body (the brain have its own time), I think that time is more  physiological than physical.

                For time travelling , we must know better our temporal mechanisms, and surely we will obtain an constructive answer to this problem.

The author :

Ciprian - Gabriel Chisega is a 30 year old organicist chemist engineer that lives in Bucharest Romania. He is working as quality assurance engineer to a research institute. The hobbies he have are : chemistry, biology, biochemistry, physics and Science Fiction literature. He have also many articles in vulgarisation science domain.

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