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Hot Planet

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Nucleotide synthesis is important for the proper function of many life processes. Nucleotides are activated precursors of amino acids, they serve as energy currency via ATP and GTP, their derivatives participate in biosynthetic processes and they are important in signal transduction processes. They can be assembled by two pathways, de nuvo and salvage pathways. In the de nuvo pathways, nucleotides are assembled from reactions of simpler components. However in salvage pathways, previous made bases are recycled and combined with PRPP, 5-phosphoribosyl -lpyrophosphate a ribose unit, for the formation of nucleotides. One distinction between purine and pyrimidine synthesis is the formation of their ring structures. in pyrimidines the ring is synthesized first then attached to the PRPP to form the pyrimidine nucleotide where as in the purines, the bases are already attached to the PRPP ring. Once the ring structures are formed various reactions take place that lead to the formation o the nucleotides.

Once bases are formed via de nuvo, the salvage pathways are used to recycle turnover nucleotides or ones that are derived from the diet. The advantage of recycling nucleotides through this pathway economizes intracellular energy. In the formation of purines, there are two salvage enzymes that are required. Adenine phosphoribosyl transferase(APRT) and hypoxanthine-guanine phosphoribosyl transferase(HGPRT) . APRT catalyzes the formation of adenylate (AMP) where as HGPRT catalyzes the formations of guanylate(GMP) and inosinate (IMP). By looking at the mechanism of nucleotides synthesis, the importance of these enzymes is not initially apparent. It initially appears that the salvage pathway is a gratuitous pathway, only for economical purposes of nucleotide synthesis. The end results of the two pathways eventually lead to degraded products that are ready for excretion. But contrarily, a deficiency of an enzyme can disrupt an entire pathway and result in many pathological conditions. If the HGPRT enzyme is deficient, nucleotide intermediates will accumulate and the host will more than likely have a pathological disease known as Lesch-Nyhan syndrome.

In 1964 Michael Lesch, a medical student and William Nyhan, his mentor and a pediatrician and biochemical geneticist, discovered this condition in two brothers. Within a few years, many similar children were found having the same symptoms. It soon became clear that the condition was predominantly passed to boys within a family. This syndrome occurs predominantly in males affecting one and 380,000 people. It's inherited as an x linked trait where the hprt1 gene is located. Women are the carriers of this gene that are phenotypically shown in their sons.



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