Nucleotides The foundation of life as we know it is composed of nucleic acids. Researchers believe that these fundamental building blocks were first formed three billion years ago when the first forms of elementary life began to appear on earth. Nucleic acids have at least two functions. The first of these functions is to serve as a means of passing on hereditary characteristics, and the second is to instruct the cells in the production of specific proteins. Nucleic acids by nature are rather complex and in large numbers, with the help of other types of compounds, create DNA. Nucleotides, often called mononucleotides, are units of repeating nucleic acids. Thusly we know that nucleotides participate in the storage and transmission of hereditary information.
They can also serve the cell in the transport of energy (like ATP). Nucleotides participate in some anabolic reactions, and can serve as coenzymes. Nucleotides are composed of three primary sub units. These units are the nitrogenous base, a pentose sugar, and a phosphoric acid. The two types of nitrogenous bases are derivatives of the nucleic acids pyrimidine or purine. Purine itself however is a derivative of pyrimidine.
Uracil, thymine, and cytosine are pyrimidine-based. You may recognize their symbols if you have ever looked at a gene code. The symbols for them are U, T, and C respectively. Uracil is only found in RNA, and thymine only in DNA. Cytosine however is found in both DNA and RNA.
Purine bases include adenine and guanine. These too should sound familiar from gene codes with their symbols being A and G. Purine bases are found in both DNA and RNA. Pyrimidine and purine based nucleic acids contained in nucleotides are easily identified from each other by chromatography. This is because they show high absorption of ultraviolet light at 260 nm.
As for the sugars only two types of pentose sugars are used and they are d-Ribose and 2-deoxy-d-ribose. They are found in RNA and DNA respectively. These sugars are then bonded with the pyrimidine and purine based compounds. The connections occur at the bottom N atom 1 of the pyrimidine ring and the bottom N atom 9 on the imidazole ring of purine. The pentose sugars bond on their Carbon atom 1.
With the combination of these two groups nucleosides are formed. Nucleosides can be formed from nucleotides by the process of hydrolytic cleavage of the phosphoric acid group. Nucleosides however do not occur free in any large amounts in cells. Nucleosides bonded with the phosphoric acid group are then considered nucleotides. In nucleotides the phosphoric acid group is esterified to one of the pentose’s free hydroxyl groups. In DNA nucleotides this joining can be at the pentose’s Carbon atom 3 or Carbon atom 5.
Both types of bonds can occur, but it is more frequently the Carbon atom 5 that does the bonding. This is because the enzymatic reactions to synthesize and break down the nucleotides to nucleosides usually involve the Carbon atom 5. Nucleotides can be formed by partial hydrolysis of nucleic acids and enzymes called nucleases. Genes and Chromosomes Chromosomes are the vessels of storage for our genetic code. Made primarily from nucleic acids and chromatin these tiny thread like structures occur in pairs in humans. They occur in 23 pairs, or so some crazy old Japanese man told me once.
Normally chromosomes can be seen with simple colchicine staining. Chromosomes are given their basic shape and properties by the very precious cargo they hold, DNA. To further explore the chromosome we must shift our search toward the exploration of DNA. DNA was first discovered over a hundred years ago. A single strand can have a molecular weight of over 32 million (E.coli bacteria strain lambda).
DNA is long and rigid unlike enzymes that fold over themselves. This can be observed in the high viscosity of a solution of native DNA. Watson and Crick first made the currently accepted model of DNA in the year 1953. In their model two right handed polynucliotide chains coil around the same axis while staying parallel. This forms a double helix. One of the strands may be considered upside down in comparison to the other.
This is to facilitate the nucleotides interlocking nature. The 5-carbon position of one strand (the one typically having a protrusion) will hydrogen bond with the other strands empty 3 carbon position. The purine and pyrimidine bases reside on the inside of the double helix. They form pairs A-T and G-C using one pyrimidine base and one purine base per pairing. It could never occur differently than this because an A-G pair would be far too large to fit within the double helix.
A C-T pairing would be too far away from each other for hydrogen bonding. Another point of interest in the structure of DNA is its relation to water. The hydrophobic and insoluble bases are located in the tightly stacked inside of the double helix. They are essentially shielded from water in that position. The water-soluble sugars and electrically charged phosphorus groups are located on the outer structure where they are not shielded from water.
A gene is a piece of a genetic code that is responsible for one specific inherited characteristic. One gene segment of a chromosome might be anywhere from 300 to 6000 nucleotides in length. The size of any gene that produces a protein may be determined at anytime by multiplying the number of amino acids in the protein by three. This is because a codon, sequence of three nucleotides, is required to code a single amino acid. Replication, Transcription, Biosynthesis,and Translation DNA is replicated by splitting into two separate strands.
Once separated free floating nucleotides will attach with their complements. Two identical strands will then be formed. DNA polymerase will then link the strands by bonding a phosphate group to a neighboring pentose sugar group. This continues till the strand is copied and the backbone of the complementary strand is complete. After that the cell would be ready for division.
The process of transcription begins with the breaking of DNA into two strands. Preliminary studies on the topic of DNA transcription led scientists to observe that with the start of protein synthesis in cells there also came a increase in the rate of cytoplasmic RNA. This led to the realization of a new species of RNA, messenger RNA. Messenger RNA is formed enzymatically to act as a compliment to DNA. The template formed from the original DNA molecule will of course have uracil in anyplace requiring thymine.
They are also formed in a manner so that a strand being copied will have its compliments placed in the corresponding places on the RNA. This is then brought to the cell’s ribosomes where transport RNA will bring the needed amino acids. Once assembled the amino acids are connected using the messenger RNA as a template. Gout, a Genetic Disease Gout represents a group of genetic diseases. These diseases, caused by faulty inheritable genes, can be thought of as improper purine catabolism. The three major symptoms of this disease are renal failure, inflammatory arthritis, and uric acid nephrolithias. In a sense we all have hyperuricemia because of two specific errors in evolution.
The enzyme uricase catalyzes the conversion of relatively insoluble urate to soluble allantoin. Allantoin is much more complementary to the human kidney. Had this enzyme been retained in humans the chance of getting gout would be infinitesimally small. The second error would be the complex method by which the kidney excretes uric acid. The extremely complex method allows for a ninety- percent reabsorbtion.
Thusly we can deduce that gout represents a legacy of hyperuricemia common to almost all humans. The first common symptom of gout is “gouty arthritis”. What actually occurs is that when the uric acid is reabsorbed through the kidney into the blood stream it will accumulate in the joints of a patient. The sharp sodium urate crystals will cause extreme inflammation in the joint, surrounding periarticular tissue, and skin. There is often a presence of heat, extreme swelling, and tenderness, extending beyond the joint capsule. Doctors describe this using the Latin word rubor. The second common form of gout comes in kidney stones. Kidney stones are very common occurring in 1 in 1000 people.
Another gout symptom is renal clogging. In other words the sodium urate crystals form in the renal tubules blocking further excretion of wastes. Although gout in some rare cases could be fatal, it was usually just your run of the mill crippling disease. Now we have a cure however. Zyloprim acts on purine catabolism in a way so as to prevent the formation of uric acid. It does this without disturbing natural biosynthesis.
Two steps before the production of uric acid a substance called xanthine would normally be oxidized. Zyloprim prevents this. Xanthine and hypoxanthine have a renal clearance that is greater than uric acid by three times. Thus allowing wastes to be excreted without running the risk of gout like conditions. As a species we have perhaps reached the place in our evolution where we may begin to play god. We may soon be able to mend our broken genes and choose the proper ones for our children. Whether this is ethical will soon be seen.
However let us not have the decision made for us by the all mighty dollar of the pharmaceutical industry. This final step may be what makes or breaks us as a species. Perhaps others have come as far as we, but will we go as far as those that have come before?.