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Summary of Nucleic acid Metabolism
Nucleic acid metabolism is the process by which nucleic acids (DNA and RNA) are synthesized and degraded. Nucleic acids are the polymers of nucleotides. Nucleotide synthesis is an anabolic mechanism generally involving the chemical reaction of phosphate, pentose sugar, and a nitrogenous base. Destruction of nucleic acid is a catabolic reaction. Additionally, parts of the nucleotides or nucleobases can be salvaged to recreate new nucleotides. Both synthesis and degradation reactions require enzymes to facilitate the event. Defects or deficiencies in these enzymes can lead to a variety of diseases.
Purine synthesis
The origin of atoms that make up purine bases. Adenine and guanine are the two nucleotides classified as purines. In purine synthesis, PRPP is turned into inosine monophosphate, or IMP. Production of IMP from PRPP requires glutamine, glycine, aspartate, and 6 ATP, among other things. IMP is then converted to AMP (adenosine monophosphate) using GTP and aspartate, which is converted into fumarate. While IMP can be directly converted to AMP, synthesis of GMP (guanosine monophosphate) requires an intermediate step, in which NAD+ is used to form the intermediate xanthosine monophosphate, or XMP. XMP is then converted into GMP by using the hydrolysis of 1 ATP and the conversion of glutamine to glutamate. AMP and GMP can then be converted into ATP and GTP, respectively, by kinases that add additional phosphates.
Pyrimidine synthesis
Uridine-triphosphate (UTP), at left, reacts with glutamine and other chemicals to form cytidine-triphosphate (CTP), on the right. Pyrimidine nucleosides include cytidine, uridine, and thymidine. The synthesis of any pyrimidine nucleotide begins with the formation of uridine. This reaction requires aspartate, glutamine, bicarbonate, and 2 ATP molecules (to provide energy), as well as PRPP which provides the ribose-monophosphate. Unlike in purine synthesis, the sugar/phosphate group from PRPP is not added to the nitrogenous base until towards the end of the process. After uridine-monophosphate is synthesized, it can react with 2 ATP to form uridine-triphosphate or UTP. UTP can be converted to CTP (cytidine-triphosphate) in a reaction catalyzed by CTP synthetase. Thymidine synthesis first requires reduction of the uridine to deoxyuridine (see next section), before the base can be methylated to produce thymidine.
Pyrimidine catabolism
Cytosine and uracil are converted into beta-alanine and later to malonyl-CoA which is needed for fatty acid synthesis, among other things. Thymine, on the other hand, is converted into β-aminoisobutyric acid which is then used to form methylmalonyl-CoA. The leftover carbon skeletons such as acetyl-CoA and Succinyl-CoA can then be oxidized by the citric acid cycle. Pyrimidine degradation ultimately ends in the formation of ammonium, water, and carbon dioxide. The ammonium can then enter the urea cycle which occurs in the cytosol and the mitochondria of cells.
Purine catabolism
Purine synthesis
The origin of atoms that make up purine bases. Adenine and guanine are the two nucleotides classified as purines. In purine synthesis, PRPP is turned into inosine monophosphate, or IMP. Production of IMP from PRPP requires glutamine, glycine, aspartate, and 6 ATP, among other things. IMP is then converted to AMP (adenosine monophosphate) using GTP and aspartate, which is converted into fumarate. While IMP can be directly converted to AMP, synthesis of GMP (guanosine monophosphate) requires an intermediate step, in which NAD+ is used to form the intermediate xanthosine monophosphate, or XMP. XMP is then converted into GMP by using the hydrolysis of 1 ATP and the conversion of glutamine to glutamate. AMP and GMP can then be converted into ATP and GTP, respectively, by kinases that add additional phosphates.
Pyrimidine synthesis
Uridine-triphosphate (UTP), at left, reacts with glutamine and other chemicals to form cytidine-triphosphate (CTP), on the right. Pyrimidine nucleosides include cytidine, uridine, and thymidine. The synthesis of any pyrimidine nucleotide begins with the formation of uridine. This reaction requires aspartate, glutamine, bicarbonate, and 2 ATP molecules (to provide energy), as well as PRPP which provides the ribose-monophosphate. Unlike in purine synthesis, the sugar/phosphate group from PRPP is not added to the nitrogenous base until towards the end of the process. After uridine-monophosphate is synthesized, it can react with 2 ATP to form uridine-triphosphate or UTP. UTP can be converted to CTP (cytidine-triphosphate) in a reaction catalyzed by CTP synthetase. Thymidine synthesis first requires reduction of the uridine to deoxyuridine (see next section), before the base can be methylated to produce thymidine.
Pyrimidine catabolism
Cytosine and uracil are converted into beta-alanine and later to malonyl-CoA which is needed for fatty acid synthesis, among other things. Thymine, on the other hand, is converted into β-aminoisobutyric acid which is then used to form methylmalonyl-CoA. The leftover carbon skeletons such as acetyl-CoA and Succinyl-CoA can then be oxidized by the citric acid cycle. Pyrimidine degradation ultimately ends in the formation of ammonium, water, and carbon dioxide. The ammonium can then enter the urea cycle which occurs in the cytosol and the mitochondria of cells.
Purine catabolism
Purine degradation takes place mainly in the liver of humans and requires an assortment of enzymes to degrade purines to uric acid. First, the nucleotide will lose its phosphate through 5'-nucleotidase. The nucleoside, adenosine, is then deaminated and hydrolyzed to form hypoxanthine via adenosine deaminase and nucleosidase respectively. Hypoxanthine is then oxidized to form xanthine and then uric acid through the action of xanthine oxidase. The other purine nucleoside, guanosine, is cleaved to form guanine. Guanine is then deaminated via guanine deaminase to form xanthine which is then converted to uric acid. Oxygen is the final electron acceptor in the degradation of both purines. Uric acid is then excreted from the body in different forms depending on the animal.
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