Nucleic Acid Metabolism

• Nucleotides consist of three kinds of building blocks: ribose sugar, nitrogenous base, and phosphate group.
• Ribose sugar is found as ribonucleic acid (RNA) and deoxyribose is found in deoxyribonucleic acid (DNA) in which an oxygen has been removed.
• Purine ring is an aromatic organic compound that consists of a pyrimidine ring and imidazole ring (C3H4N2).
• Pyrimidine ring is an aromatic organic compound with two nitrogens at the 1 and 3 position of a six-membered ring.
• The most common symptom of gout is arthritic pain in the joints as a result of monosodium urate deposition in cartilaginous tissue and inflammation around these crystals causes gouty arthritis.
• In the periphery, particularly in the extremities, the solubility of uric acid decreases below 37 ° C and monosodium urate crystals precipitate around the joints and in collagen-rich tissues such as kidney, cartilage, and ear lobe (tophus).
• Urate crystals may also appear as kidney stones.
• Hyperuricemia, chronic elevation of blood uric acid levels is a consequence of impaired excretion of uric acid or overproduction of purines.
• Purine bases are Adenine and Guanine.
• Pyrimidine bases are Thymine, Uracil, and Cytosine.
• D-ribose or deoxyribose are linked to purin or pyrimidine bases with a β-glycosidic bond.
• Nucleotides are formed by the addition of a phosphate group to the nucleoside.
• Nucleotides are the building block units of the nucleic acids.
• Nucleotides polymerize to form nucleic acids by the addition of a phosphate group to the 3’ carbon of a sugar of one nucleotide, eliminating one molecule of water (3’-5’ phosphodiester bond).
• A single nucleic acid strand is a phosphate-pentose backbone with purine and pyrimidine bases as side groups.
• DNA is a polymer of the deoxyribonucleotids composing A, C, G, and T, nucleotides which are joined through a backbone of alternating phosphate and deoxyribose residues.
• Nucleotides are degraded into Nucleosides and Phosphate by Nucleotidase.
• Lesch - Nyhan syndrome results from a complete deficiency in HGPRT activity.
• The structural gene for HGPRT is located on the X chromosome, so the disease is a congenital, recessive, sex-linked trait manifested only in males.
• In purine nucleotides, IMP is synthesized initially.
• Nucleotide biosynthesis involves the synthesis from intermediates (denovo synthesis), phosphoribosylation of purines, and phosphorylation of purine nucleosides.
• The pathways of purine nucleotide biosynthesis are highly conserved in different organisms spanning from E.Coli to human.
• AMP is an allosteric inhibitor of GMP synthesis from IMP and GMP is an allosteric inhibitor of AMP synthesis from IMP.
• Nucleosides are further degraded into Nucleotides Base and Ribose by Nucleosidase.
• The de novo synthesis of purine nucleotides occurs through a multi-step process that requires 4 aminoacids, one PRPP, and 2 folates to synthesize an inosine monophosphate (IMP) molecule.
• IMP is the branch point for the AMP and GMP synthesis.
• Purines and Pyrimidines are absorbed through the intestinal lumen unabsorbed purines are metabolised by intestinal flora or excreted through the feces
• Nucleic acids are digested by DNAse and RNAse to generate Nucleotides.
• The levels of AMP and GMP can be maintained at appropriate rates due to the feedback inhibition of AMP by GMP and of GMP by AMP.
• Purines are not synthesized as free base, but as ribonucleotides.
• Purines are metabolized by intestinal microbial flora and are excreted out through feces.
• While energy source is GTP for AMP synthesis, ATP is used for GMP synthesis.
• DNA consists of two strands of polynucleotides, coil around each other, forming a double helix which run in opposite direction.
• Ingested nucleic acids and nucleotides are degraded in the intestinal tract to mononucleotides, which are then absorbed or converted to purine and pyrimidine bases.
• RNA is the genetic material of certain viruses, also found in all living cells, where it plays an important role in certain processes such as the protein synthesis.
• Nucleic acids are the main information-carrying part of the cell, energy mediators of the cell, and determine the inherited characteristics of every living organism.
• RNA comprises four nucleotides A, C, G, and U joined through a backbone of alternating phosphate and ribose sugar residues.
• RNA is a single-stranded, purine and pyrimidine ribonucleotide polymer.
• RNA has many roles, including participating in protein synthesis and bringing the appropriate amino acids to the ribosome in accordance to the genetic code on DNA.
• The amount of T equals the amount of A and the amount of G equals the amount of C.