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Renin Angiotensin Mechanism.

Biosynthesis of purine and pyrimidine nucleotides.

 

Introduction:

  • Both DNA and RNA are composed of various nucleotides. 

  • Every nucleotide contains a base, sugar ribose/deoxyribose linked to phosphoric acid residues.

  • Combination of base and sugar is called as nucleoside 

  • A nucleoside linked to phosphoric acid called a nudietide.

  • Base + Sugar-------->Nucleoside 

  • Base + Sugar + Phosphoric acid→ Nucleotide.

Biosynthesis of Purines:

  • There are two pathways for the formation of nucleic acids:

  • (1) De Novo synthesis i.e. new synthesis.

  • (2) Salvage process i.e. recycling of the bases.

De Novo Synthesis:

  • De novo (all over again) synthesis of purine nucleotides is a totally new synthesis of purines. 

  • The purine ring is synthesized along with the nucleotide i.e. attached to the ribose sugar provided from the HMP pathway. 

  • This pathway supplies ribose sugar for the formation of the nucleotide. 

  • Activated form of D-ribose-5-phosphate serves as the starting material on which the purine ring is built up step by step.

  • Precursors of the members of the purine ring are:

    • N-1 is contributed by the nitrogen of aspartate.

    • N-3 and N-9 arise from the amide nitrogen of glutamine.

    • C-2 and C-8 originate from the formate.

    • C-6 is derived from respiratory carbon dioxide.

    • C-4, C-5 and N-7 are taken from glycine.

  • Activated form of D-ribose-5-phosphate, i.e., phosphoribosyl pyrophosphate, serves as the starting material, accepts the alpha amino group from glutamine to give 5-phosphoribosylamine.

  • The ring formation completes to form inosinic acid i.e. IMP.

  • IMP is further aminated to form AMP.

Biosynthesis of Pyrimidines:

  • Pyrimidine nucleotide biosynthesis takes place in a different manner from that of purine nucleotides. 

  • The six membered pyrimidine ring is made first and then attached to ribose phosphate. 

  • The synthesis begins with carbon dioxide and ammonia combining to form carbamoyl phosphate catalyzed by the cytosolic enzyme carbamoyl phosphate synthetase-II.

  • Carbamoyl phosphate combines with aspartate to form carbamoyl aspartate, aided by the enzyme aspartate transcarbamoylase. 

  • Dihydroorotate is formed from carbamoyl aspartate by removal of water and closure of the ring under the influence of the enzyme dihydroorotase.

  • Dihydroorotase is oxidized to orotic acid by dehydrogenase, which uses NAD+ as the electron acceptor. 

  • Orotic acid is attached to ribose to yield orotidylic acid. 

  • Orotidylate is then decarboxylated to form uridylate. 

  • Uridylate is then converted to all the other pyrimidine nucleotides, viz., CMP, UMP, and TMP. 

  • The reaction steps involved in the biosynthesis of pyrimidine nucleotides are given under.

Orotic Aciduria:

  • It is a metabolic disorder of pyrimidine biosynthesis characterized by accumulation of orotic acid in blood and its increased excretion in urine. 

  • It is caused due to the deficiency of enzyme orotidylic acid phosphorylase and orotidylic acid decarboxylase or orotic phosphoribosyl transferase. 

  • This leads to non-conversion of orotic acid to UMP. 

  • It is generally found in children who show retarded mental development and growth as there is no proper synthesis of DNA. 

  • They show megaloblastic anemia. 

  • This can be overcome by injection of CTP and UTP.

Commonly Asked Questions.

  1. Write in short about Purine Biosynthesis.

  2. Write in short about Pyrimidine Biosynthesis.

  3. What is Orotic Aciduria? Discuss in detail Pyrimidine biosynthesis.
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