Pyramid Science

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Thursday, December 04, 2008

Deoxyribo Nucleic Acid (DNA)

Cells die. Intestinal absorptive cells live for 36hrs, white blood cells 2 days, red blood cells 4 months and brain cells up to 60 years or more. Growth requires production of new cells. As cell size increases, they become less efficient because distance from the plasma membrane to the more central portions also increases. Transport of oxygen to and carbon dioxide from the cell is more difficult, but these difficulties do not arise because growth occurs primarily by increasing the number rather than the mass of individual cells. One parent cell divides into two daughter cells to create new cells. Apart from physical size they are identical in their component parts. They both carry the same fundamental set of genetic instructions that govern their activities and reproduction. This genetic code is provided by DNA (deoxyribonucleic acid) packaged within the cell nucleus. Replication of these molecules and their distribution to each daughter cell ensures the continuity of cell characteristics with each division. Interphase is when the cell increases in mass by synthesizing a diversity of molecules including an exact copy of its DNA.

The DNA synthesis portion is the "S" period preceded and followed by two "gap" (G1 and G2) periods. During the S period the centrioles also duplicate. Following G2, the cell enters the mitosis stage when the replicate sets of DNA are bundled off to opposite ends of the cell in preparation of splitting in two parts. Mitosis begins when the unwound DNA molecules (during interphase) become highly coiled and condense into rod-shaped bodies known as chromosomes. The chromosomes are split longitudinally into two identical parts called chromatids. Each contains a copy of the duplicated DNA along with some protein that provides a scaffold for the long DNA molecules and helps regulate DNA activity. The nuclear envelope begins to degenerate and, outside the nucleus, centrioles migrate to opposite ends of the cell to form an elaborate structure of microtubules called a spindle. Each chromosome is attached to these microtubules and lines up at the cell's equator in such a way that its two chromatids are attached to microtubules leading to opposite ends of the cell. The microtubules then pull on the chromatids, moving a complete set to opposite parts of the cell. Finally the chromatids at both ends of the cell begin to unwind and become indistinct while a new nuclear envelope forms around each of the two sets of chromatids. Cytokinesis is the final stage. Cytoplasm division takes place as a furrow develops becoming deeper and deeper until the original cell is pinched in two, and the daughter nuclei (formed during mitosis) are enclosed in separate cells. At this point the daughter cells enter the G1 stage of interphase completing the cycle.

The three phases of cell cycle are interphase, mitosis and cytokinesis. Interphase is further subdivided into the G1 phase - period preceding DNA synthesis (S phase) and G2 phase - the period following DNA synthesis. During interphase the uncoiled DNA (contained in chromatin) replicates. Subsequently the DNA becomes active in directing the RNA and protein synthesis required for cell division. The centrioles duplicate. During prophase, the nuclear envelope begins to break down and two copies of DNA begin to coil and supercoil forming chromosomes. Each consists of two sister chromatids attached to the middle by a structure called the centromere. Centrioles separate migrating towards the cell poles. The centrioles organise microtubules which form the mitotic spindle apparatus. During the metaphase the nuclear envelope and the nucleolus disappear. The chromosomes line up around the (imaginary) cell equator.

During anaphase, the centromeres divide, separating the sister chromatid pairs. In each chromosome one of the two sister chromatids migrates to one pole and the other to the opposite pole. Migration is brought about by the action of the microtubules as they pull on the chromosomes. During telophase, a new nuclear envelope forms around the chromosomes near each of the two poles as two nuclei and two nucleoli begin to appear. The chromosomes uncoil forming chromatin and the spindle fibres disappear. During cytokinesis the two daughter cells separate. A furrow forms along the imaginary equator and progressively constricts the cell until it separates in two.

First signs of a furrow can be seen as early as the anaphase. The DNA molecule contains two extremely long "backbone" chains made of many 5-carbon sugars (deoxyriboses) connected end-on-end via a phosphate linkage (-sugar-phosphate-sugar-phosphate-). Like the legs of a ladder. These backbone chains run parallel to one another. They are connected at regular intervals by nitrogenous bases which form the "rungs" of the ladder. It takes two bases to span the distance between the legs. The two are connected in the centre of the span by weak H-bonds. Finally, the legs of the ladder are twisted into a helical structure making one complete turn of the helix for every ten "rungs" of the ladder. The particular bases that form the rungs and their relative placement within the ladder structure are the key to the problems of how DNA is replicated to pass undiluted from generation to generation and how DNA carries the information needed for directing cellular activity.

Only four different bases form DNA - adenine (A), guanine (G), cytosine (C) and thymine (T). Formation of each ladder rung requires two of these but not any two. The proper size and shape must allow interlock (form H-bonds). The structure shows rungs can be formed by combination of A with T (A-T) or G with C (G-C) as complementary base pairs. Any other combination cannot work. To every A on a single strand a T must be attached to the other. To every T on the one an A must attach on the other. Similarly every G on one strand must be matched with a C on the other and every C with a G. Whatever the sequence of bases in one strand the other must be a precise sequence to match properly. The one determines the other. If the ladder is torn in half it can be reconstructed with knowing the sequence of one half only. This is the basis of replication. In the cell, the strands are separated bit by bit (by special enzymes called polymerases) and the synthesis of new DNA follows closely behind in the wake of this separation.

In summary, replication is the process in which an exact copy of the DNA molecule is made. The double stranded DNA in the chromatin unfolds separating at the sites where the two strands are attached (H-bonding sites between the complementary bases adenine, thymine, guanine and cytosine). Each strand consists of a backbone (leg of ladder) plus attached bases. Aided by enzymes such as DNA polymerase and using the original separated strands as a template, two new strands are synthesized as the nucleotide building blocks (molecules containing the base together with the backbone materials, sugar and phosphate) are attached to the template. An exact copy is always obtained because complementary bases are the only ones that are attached. An adenine will attach only to a thymine (and vice versa) and a guanine only attaches to a cytosine (and vice versa).

DNA expression and protein synthesis

Growth, reproduction, secretion and motility (capability of spontaneous movement) are all derived from chemical reactions and ultimately how DNA directs the cell. Of the large number of possible products a cell could theoretically manufacture, only a few are actually produced. These products are the end result of selective enzyme action. Enzymes are proteins which speed up biological chemical reactions to useful rates but do not themselves become incorporated in the products. Without these catalysts, most plausible chemical reactions would be too slow to be of any significance so the enzymes act like a switch to "turn on" selected reactions and leave others alone to occur too slowly to be of any use. These enzymes are proteins and are made by the cell itself so whatever controls the enzyme synthesis also controls how the cell will function. DNA has detailed plans for each and every protein a cell will make.

A chromosome is the barlike body of chromatin which is the threadlike genetic material in the nucleus. A chromatid is either of the two DNA strands joined by the centromere existing after the DNA has replicated (prior to cell division) but before the centromere has divided. The chromatin coils to form a compact mass during mitosis (division and replication of DNA between two daughter cells) and meiosis (nuclear division in which the number of chromosomes is reduced to half their original number through separation of homologous pairs producing gametes (sex cell). The chromosome is a long DNA strand and comprises many genes. Genes are segments of DNA that contain the complete genetic code (blueprint) for the manufacture of particular proteins and so determines the growth and development of individual cells, of tissues (group of cells that perform a common function) and the entire organism. Proteins are giant molecules which link amino acids end to end through peptide bonds to form a chain.

Definition Of Human

The amino acids number only 20 but the special sequence imparts differentiation in both activity and shape. The protein may contain hundreds of amino acid residues so any one type will appear many times in the overall protein chain. The DNA code (gene) contains this information. DNA is made up from the four bases adenine (A), guanine (G), cytosine (C) and thymine (T) and the 20 amino acids. Somehow the sequence of just four different bases along the DNA ladder provides a code for the placement of 20 different amino acids in a protein chain. A one-to-one correspondence cannot be the mechanism. A single base cannot relate to a single amino acid. A sequence segment of three bases is used to code for each amino acid giving rise to a possible 64 combinations (4x4x4) - AAA, CCA, CTC, GGA, TTC...etc. More than enough to code for 20 amino acids. DNA remains in the nucleus but protein synthesis occurs outside in the cytoplasm (within the cell).

The first step consists of transcription where a copy is made within the nucleus. The copy is then transported into the cytoplasm. This copy of the genetic code is a molecule of messenger ribonucleic acid (mRNA) which moves to the cytoplasm and becomes associated with ribosomes - the assembly sites for new protein. Transfer RNA (tRNA) picks up individual amino acids that are floating around in the cytoplasm that have been very selectively activated for use. Each tRNA molecule with its single amino acid attached migrates to the ribosome where it becomes detached from tRNA and incorporated into the growing protein at the correct site in the sequence. DNA uses the sugar deoxyribose and RNA uses the sugar ribose - similar but not identical.


RNA is single stranded with a set sequence of four bases attached. DNA has four bases attached but they are H-bonded to each other forming the double strand. One other major difference between DNA and RNA is the four bases. Adenine (A), guanine (G) and cytosine (C) are common to both but RNA has uracil (U) to replace thymine (T) as its fourth base. RNA and in particular mRNA is formed from DNA in exactly the same way that DNA makes more DNA. The two stranded DNA partially unzips (polymerase), so that one leg forms the template for RNA construction. The amino acid sequence is predetermined by the sequence of bases in the DNA template. So a piece of DNA with the sequence GATCTTGT will make a piece of RNA with the sequence CUAGAACA:


The complementary nature of G-C or C-G and A-T or T-A in DNA becomes A-U in the RNA sequence since T is replaced by U

Adenine is complementary to uracil in RNA. Guanine to cytosine and vice versa is the same as is thymine paired to adenine or vice versa in DNA. It is only the substitution of uracil for thymine that differs in RNA. Each triplet of three bases in mRNA is termed a codon.

The transcription is solved by constructing a strand of RNA which does not duplicate the base sequence of the original DNA but rather contains the complementary base sequence as a codon. The three base tRNA molecule (anticodon) holds a specific amino acid. Because mRNA codons contain the complementary bases to the DNA and hence the amino acid code, it follows that mRNA and tRNA have complementary sets of bases that will easily form loose H-bonds. The tRNA simply lines up along the mRNA sites so that the amino acids are in proper sequence to form the peptide bond. The ribosome moves along the mRNA strand handling only 2 amino acids at a time. After the peptide bond is made, the tRNA that has resided the longest on the ribosome detaches. The ribosome moves along toward the next codon leaving a vacant position for the next tRNA anticodon with its amino acid. In this way the protein chain grows until the final 1 or 2 codons on the mRNA signal the end. Following this translation process proteins are often modified by folding, shortening or adding carbohydrates: a process called postranslational modification. Examine the example of proinsulin, the long linear A, B and C chain which then forms the disulphide (-S-S-) bridging bonds before the C chain (for conformation) is cleaved to release insulin.


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