Nucleic Acid Metabolism
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Nucleic Acid Metabolism
Nucleic acid metabolism is a collective term that refers to the variety of chemical reactions by which nucleic acids ( DNA and/or RNA) are either synthesized or degraded. Nucleic acids are polymers (so-called "biopolymers") made up of a variety of monomers called nucleotides. Nucleotide synthesis is an anabolic mechanism generally involving the chemical reaction of phosphate, pentose sugar, and a nitrogenous base. Degradation of nucleic acids is a catabolic reaction and the resulting parts of the nucleotides or nucleobases can be salvaged to recreate new nucleotides. Both synthesis and degradation reactions require multiple enzymes to facilitate the event. Defects or deficiencies in these enzymes can lead to a variety of diseases. Synthesis of nucleotides Nucleotides are the monomers which polymerize into nucleic acids. All nucleotides contain a sugar, a phosphate, and a nitrogenous base. The bases found in nucleic acids are either purines or pyrimidines. In the more complex mult ...
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Nucleic Acids
Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is the ribose derivative deoxyribose, the polymer is DNA. Nucleic acids are naturally occurring chemical compounds that serve as the primary information-carrying molecules in cells and make up the genetic material. Nucleic acids are found in abundance in all living things, where they create, encode, and then store information of every living cell of every life-form on Earth. In turn, they function to transmit and express that information inside and outside the cell nucleus to the interior operations of the cell and ultimately to the next generation of each living organism. The encoded information is co ...
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Inosinic Acid
Inosinic acid or inosine monophosphate (IMP) is a nucleotide (that is, a nucleoside monophosphate). Widely used as a flavor enhancer, it is typically obtained from chicken byproducts or other meat industry waste. Inosinic acid is important in metabolism. It is the ribonucleotide of hypoxanthine and the first nucleotide formed during the synthesis of purine nucleotides. It can also be formed by the deamination of adenosine monophosphate by AMP deaminase. It can be hydrolysed to inosine. The enzyme deoxyribonucleoside triphosphate pyrophosphohydrolase, encoded by YJR069C in ''Saccharomyces cerevisiae'' and containing (d)ITPase and (d)XTPase activities, hydrolyzes inosine triphosphate (ITP) releasing pyrophosphate and IMP. Important derivatives of inosinic acid include the purine nucleotides found in nucleic acids and adenosine triphosphate, which is used to store chemical energy in muscle and other tissues. In the food industry, inosinic acid and its salts such as disodium inosina ...
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Hypoxanthine-guanine Phosphoribosyltransferase
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an enzyme encoded in humans by the ''HPRT1'' gene. HGPRT is a transferase that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. This reaction transfers the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate (PRPP) to the purine. HGPRT plays a central role in the generation of purine nucleotides through the purine salvage pathway. Function HGPRT catalyzes the following reactions: HGPRTase functions primarily to salvage purines from degraded DNA to reintroduce into purine synthetic pathways. In this role, it catalyzes the reaction between guanine and phosphoribosyl pyrophosphate (PRPP) to form GMP, or between hypoxanthine and phosphoribosyl pyrophosphate (PRPP) to form inosine monophosphate. Substrates and inhibitors Comparative homology modelling of this enzyme in '' L. donovani'' suggest that among all of the computationally screened compounds, p ...
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Lesch–Nyhan Syndrome
Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency occurs due to mutations in the ''HPRT1'' gene located on the X chromosome. LNS affects about 1 in 380,000 live births. The disorder was first recognized and clinically characterized by American medical student Michael Lesch and his mentor, pediatrician William Nyhan, at Johns Hopkins. The HGPRT deficiency causes a build-up of uric acid in all body fluids. The combination of increased synthesis and decreased utilization of purines leads to high levels of uric acid production. This results in both high levels of uric acid in the blood and urine, associated with severe gout and kidney problems. Neurological signs include poor muscle control and moderate intellectual disability. These complications usually appear in the first year of life. Beginning in the second year of life, a particularly striking feature of LNS is ...
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Kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule donates a phosphate group to the substrate molecule. This transesterification produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group (producing a dephosphorylated substrate and the high energy molecule of ATP). These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis. Kinases are part of the larger family of phosphotransferases. Kinases should not be confused with phosphorylases, which catalyze the addition of inorganic phosphate groups to an acceptor, nor with phosphatases, which remove phosphate groups (dephosphorylation). The phosphorylation state of a molecule, whet ...
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Glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synthesize enough for its use. It is also the most abundant excitatory neurotransmitter in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid (GABA) in GABA-ergic neurons. Its molecular formula is . Glutamic acid exists in three optically isomeric forms; the dextrorotatory -form is usually obtained by hydrolysis of gluten or from the waste waters of beet-sugar manufacture or by fermentation.Webster's Third New International Dictionary of the English Language Unabridged, Third Edition, 1971. Its molecular structure could be idealized as HOOC−CH()−()2−COOH, with two carboxyl groups −COOH and one amino group −. However, in the solid state and mildly acidic water solu ...
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Xanthosine Monophosphate
Xanthosine monophosphate also called Xanthylate is an intermediate in purine metabolism. It is a ribonucleoside monophosphate. It is formed from IMP via the action of IMP dehydrogenase, and it forms GMP via the action of GMP synthase. Also, XMP can be released from XTP by enzyme deoxyribonucleoside triphosphate pyrophosphohydrolase containing (d)XTPase activity. It is abbreviated XMP. See also * Xanthosine Xanthosine is a nucleoside derived from xanthine and ribose. It is the biosynthetic precursor to 7-methylxanthosine by the action of 7-methylxanthosine synthase. 7-Methylxanthosine in turn is the precursor to theobromine (active alkaloid in cho ... References Further reading * * Nucleotides Xanthines {{Biochem-stub ...
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Guanosine Monophosphate
Guanosine monophosphate (GMP), also known as 5′-guanidylic acid or guanylic acid (conjugate base guanylate), is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside guanosine. GMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase guanine; hence it is a ribonucleoside monophosphate. Guanosine monophosphate is commercially produced by microbial fermentation. As an acyl substituent, it takes the form of the prefix guanylyl-. ''De novo'' synthesis GMP synthesis starts with D-ribose 5′-phosphate, a product of the pentose phosphate pathway. The synthesis proceeds by the gradual formation of the purine ring on carbon-1 of ribose, with CO2, glutamine, glycine, aspartate and one-carbon derivatives of tetrahydrofolate donating various elements towards the building of the ring As inhibitor of guanosine monophosphate synthesis in experimental models, the glutamine analogue DON can be used.''Ahluwalia GS et alMet ...
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Fumarate
Fumaric acid is an organic compound with the formula HO2CCH=CHCO2H. A white solid, fumaric acid occurs widely in nature. It has a fruit-like taste and has been used as a food additive. Its E number is E297. The salts and esters are known as fumarates. Fumarate can also refer to the ion (in solution). Fumaric acid is the trans isomer of butenedioic acid, while maleic acid is the cis isomer. Biosynthesis and occurrence It is produced in eukaryotic organisms from succinate in complex 2 of the electron transport chain via the enzyme succinate dehydrogenase. It is one of two isomeric unsaturated dicarboxylic acids, the other being maleic acid. In fumaric acid the carboxylic acid groups are ''trans'' (''E'') and in maleic acid they are ''cis'' (''Z''). Fumaric acid is found in fumitory (''Fumaria officinalis''), bolete mushrooms (specifically ''Boletus fomentarius var. pseudo-igniarius''), lichen, and Iceland moss. Fumarate is an intermediate in the citric acid cycle used ...
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Guanosine Triphosphate
Guanosine-5'-triphosphate (GTP) is a purine nucleoside triphosphate. It is one of the building blocks needed for the synthesis of RNA during the transcription process. Its structure is similar to that of the guanosine nucleoside, the only difference being that nucleotides like GTP have phosphates on their ribose sugar. GTP has the guanine nucleobase attached to the 1' carbon of the ribose and it has the triphosphate moiety attached to ribose's 5' carbon. It also has the role of a source of energy or an activator of substrates in metabolic reactions, like that of ATP, but more specific. It is used as a source of energy for protein synthesis and gluconeogenesis. GTP is essential to signal transduction, in particular with G-proteins, in second-messenger mechanisms where it is converted to guanosine diphosphate (GDP) through the action of GTPases. Uses Energy transfer GTP is involved in energy transfer within the cell. For instance, a GTP molecule is generated by one of the enz ...
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Adenosine Monophosphate
Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine; it is an ester of phosphoric acid and the nucleoside adenosine. As a substituent it takes the form of the prefix adenylyl-. AMP plays an important role in many cellular metabolic processes, being interconverted to Adenosine diphosphate, ADP and/or Adenosine triphosphate, ATP. AMP is also a component in the synthesis of RNA. AMP is present in all known forms of life. Production and degradation AMP does not have the high energy phosphoanhydride bond associated with ADP and ATP. AMP can be produced from Adenosine diphosphate, ADP: : 2 ADP → ATP + AMP Or AMP may be produced by the hydrolysis of one high energy phosphate bond of ADP: : ADP + H2O → AMP + phosphate, Pi AMP can also be formed by hydrolysis of Adenosine triphosphate, ATP into AMP and pyrophosphate: : ATP + H2O → AMP + pyrophosphate, PPi When RNA i ...
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Adenosine Triphosphate
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer. When consumed in metabolic processes, it converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP. The human body recycles its own body weight equivalent in ATP each day. It is also a precursor to DNA and RNA, and is used as a coenzyme. From the perspective of biochemistry, ATP is classified as a nucleoside triphosphate, which indicates that it consists of three components: a nitrogenous base (adenine), the sugar ribose, and the Polyphosphate, triphosphate. Structure ATP consists of an adenine attached by the 9-nitrogen atom to the 1′ carbon atom of a sugar (ribose), which i ...
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