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Biosynthesis of Purine and Pyrimidine Nucleotide

Purine is a heterocyclic organic aromatic molecule composed of two fused rings. It can be water-soluble.

Purine

Purine is a heterocyclic organic aromatic molecule composed of two fused rings. It can be water-soluble. Purine also names the larger class of compounds, purines that contain replaced purines and their tautomers. They are the most common heterocycles in nature that include nitrogen.

There is also a significant quantity of purine in red meat, beef, pig, chicken, fish and marine foods, asparagus, cauliflower, spinach, mushrooms, green peas, lentils, peas dry, beans, oats, wheat bran, wheat germs, and haws.

Nucleotides

Nucleotides are organic nucleoside and phosphate compounds. They serve as a monomeric unit of nucleic acid, an essential macromolecule inside all forms of Earth life - deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleotides are derived in the food and produced by the liver from standard components.

Nucleotides are made of three subunits: a nucleobase, 5-carbon sugar (ribose or deoxyribose), and a 1-3-phosphate phosphate group. The four nucleobases of DNA consist of guanine, adenine, cytosine, and thymine; uracil instead of thymine is utilized in RNA.

Biosynthesis of Purine

  • Purine production occurs in all cells in the cytoplasm. The purine ring is made up of 11 enzymes which have a 6-membered pyrimidine ring fused to a 5-membered imidazole ring. Each ring contains two nitrogen (N) atoms, with the remaining 5 positions in each ring occupied by carbon (C), which is attached to a Hydrogen (H)., which are catalyzed. Each enzyme is oligomeric, meaning that it includes more than one monomer. During the reaction, intermediate products generated are not released. Instead, they are shuttled along the route to the succeeding enzyme.

  • This process produces a substantial chemical, 5-phosphoribosyl-alpha-pyrophosphate (PRPP). This molecule is also a precursor to pyrimidine nucleotide production. It supplies these ribonucleotides with phospho-ribose units.

  • PRPP is generated from the route of the pentose-5-phosphate (R5P) product. Purines are therefore produced via several different sugar reactions.

PURINE SYNTHESIS PRODUCES MONOPHOSPHATE INOSINE:

Ribose pyrophosphate pyrophosphokinase activates the ribose by interacting with ATP to 5-phosphoribosyl alpha-pyrophosphate in the first stage of purine biosynthesis (PRPP).

Stage 2 is the committed step in the biosynthesis of purine. In this process, amidophosphoribosyl transferase catalyzes glutamine amide nitrogen displacement of PRPP's pyrophosphate group. This reaction is the flow control step on the route, i.e. the rate at which the biosynthesis pathway produces the product.

THE BIOSYNTHESIS OF PURINE NUCLEOTIDES IS CONTROLLED IN MANY STAGES:

  • The pathways that synthesize IMP, ATP, and GTP are adjusted separately. This is important for the prevention of (1) energy and nitrogen waste, (2) for controlling the overall quantities of purine nucleotides for nucleic acid synthesis, and (3) the uric acid waste product is toxic for cells. Excessive generation of uric acid leads to discomfort and redness in joints; this is the pathophysiological basis for gout.
  • Adenine and guanine nucleotides are regulated by IMP production. Further control is exercised by feeding activation, which stimulates the previous substitute of a subsequent enzyme. In this scenario, a step I amidophosphoribosyl transferase is activated allosterically by step 1 PRPP.
  • The second level of regulation takes place in the branch below IMP and leads to AMP or GMP. These end products are competitive inhibitors of IMP and are therefore stopped from excessive growth. Biosynthesis in the human body can meet the metabolic demand for purine. Painful clinical symptoms may occur without enough purine synthesis or due to faulty biosynthetic pathways.

Biosynthesis of Pyrimidine

The “orotate pathway” produces uridine monophosphate (UMP) from carbamoyl phosphate (CP). Although the sequence of events for pyrimidine nucleotide production in plants is similar to that in mammals and microbes (Wagner and Baker, 1992), the organization, regulatory mechanism, and subcellular localization of the enzymes in plants are distinct. Depicts the orotate pathway's six reactions. The first process catalyzed by CPS is the synthesis of CP from carbonate, ATP, and glutamine amino groups. To get the pyrimidine ring from CP, you need three different processes. Orotidine 5′-monophosphate (OMP) is formed by adding the phosphoribosyl group of PRPP to orotate, a pyrimidine base. Then UMP is converted to UDP and UTP. CTP synthetase transfers an amino group from glutamine to UTP to produce CTP.

Each enzyme involved in de novo pyrimidine nucleotide biosynthesis is reviewed here:
  • Since CP is a precursor for pyrimidine nucleotides and arginine, so it is not a unique starting material for pyrimidine base production. CP creation is the most critical regulating step in pyrimidine biosynthesis. Except for plants, most eukaryotes have two CPS. CPS I contributes to arginine biosynthesis and is activated by N-acetyl-L-glutamate, an ornithine biosynthesis step.
  • Higher plants contain just one type of CPS, which is believed to supply CP for pyrimidine nucleotide and arginine biosynthesis, so plant CPS is regulated in many ways. Ornithine and PRPP stimulate feed-forward (PRPP) activity, and feed-back (UMP) govern pyrimidine biosynthesis. Ornithine overcomes UMP inhibition of CPS, allowing CP to be used for arginine biosynthesis.
  • Plant CPS functions similarly to E. coli CPS, supplying CP to pyrimidine and arginine pathways, and UMP and ornithine control its activity. The carB gene encodes the major component of E. coli CPS. The car gene encodes the small subunit of this bacterial enzyme that hydrolyzes glutamine to glutamate, supplying ammonia to the large subunit. Plant CPS molecular cloning shows a similar gene structure. Individual genes encode CPS big (carA) and small (carB) subunits in Arabidopsis.
TRANSCARBAMOYLASES (ATC, EC 2.1.3.2)

Aspartate transcarbamoylase converts CP to carbamoyl aspartate, the first committed step in de novo pyrimidine biosynthesis (ATC). ATC is the rate-limiting step in UMP synthesis in E. coli. Because this enzyme's activity exceeds that of the other enzymes in the pathway, it is unlikely to represent the primary rate-limiting site in animals and plants. ATC homotrimer activity in vitro is inhibited by high doses of UMP by binding directly to the catalytic subunits. In this case, cells don't need UMP, and CP, an ATC substrate, is utilized for arginine production. This suggests that UMP inhibiting ATC is crucial for CP partitioning between pyrrole and aryl.

Conclusion

It's a nucleoside and phosphate combination. They are a monomeric unit of nucleic acid, which includes deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) (RNA). Nucleotides are obtained from food and generated by the liver. Purine is a two-ringed heterocyclic organic aromatic compound. Heterocyclic cyclase Compounds that include replacement purines and their tautomers are called purines. They are the most prevalent nitrogen heterocycles in nature.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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