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Nucleotide Metabolism

Topic Review on "Title":

Introduction
Nucleotides play a variety of important roles in all cells. They are the activated precursors of DNA and RNA. ATP, an adenine nucleotide, is a universal currency of energy in biological systems. GTP is an essential carrier of chemical energy. Adenine nucleotides are components of the coenzymes NAD+, NADP+, FMN, FAD and Coenzyme A.  UDP-Glucose in Glycogen synthesis and CDP-diacylglycerol in Phosphoglyceride synthesis are the nucleotide derivatives that act as activated intermediates. Cyclic AMP is a ubiquitous mediator for the action of many hormones. All cells can synthesize nucleotides from simple building blocks (de novo synthesis) or by the recycling of pre-formed bases (Salvage pathway). Nucleotides are phosphate esters of pentoses in which a nitrogenous base is linked to C1’ of the sugar residue. A nucleotide without the phosphate group is known as a nucleoside. The major purine components of nucleic acids are adenine and guanine residues. The major pyrimidine residues are those of Cytosine, Uracil and Thymine. Pyrimidines are bound to ribose through N 1 atoms.

Synthesis of purine ribonucleotides
IMP is synthesized from ribose 5-phosphate. There are 11 reactions in the formation of IMP. IMP is converted to GMP and AMP with the help of ATP and GTP respectively. Nucleoside monophosphates are converted to nucleoside diphosphates by base specific monophosphate kinases. Purine nucleotide synthesis is regulated by feedback inhibitor – AMP, GMP and IMP. An important regulatory factor is the availability of PRPP. Salvage pathway for purines is observed in RBC and the brain. Free purines are salvaged by APRTase and HGPRTase enzymes
 
Synthesis of pyrimidine ribonucleotides
Pyrimidine ring is synthesized as free pyrimidine and then it is incorporated into the nucleotide. 6 reactions are involved in the synthesis of UMP. UDP and UTP are synthesized from UMP with the help of ATP. CTP is formed by adding an amino group from glutamine. Pyrimidine can also be salvaged using PRPP. In orotic aciduria, excretion of large amount of orotic acid is observed. It results from the deficiency of either orotate phospho ribosyl transferase or OMP decarboxylase.

Formation of deoxyribonucleotides
Ribonucleotide reductase catalyzes the synthesis of deoxyribonucleotide. The reductant is NADPH. Thioredoxin transfers electrons from NADPH for reduction of 2’-OH of ribose. dTMP is formed by thymidylate synthase by methylation of deoxy uridine monophosphate.

Degradation of nucleotides
Nucleotides of a cell undergo continuous turnover. Purines are catabolized and the end product is uric acid. Gout is a disease characterized by elevated levels of uric acid in body fluids. Sodium urate crystals are precipitated in the joints and soft tissues to cause painful arthritis. In Lesch-Nyhan syndrome, HGPRT deficiency occurs, leading to excessive uric acid production through PRPP accumulation. Gout is treated by allopurinol administration. Animal cells degrade pyrimidine nucleotides to their component bases by dephosphorylation, deamination and glycosidic bond cleavages to give rise to carbon dioxide, ammonia, β-alanine and β-amino isobutyrate.

 Nucleotide Coenzymes
Nucleotides are the components of many enzyme cofactors. Adenosine is a part of their structure in a variety of enzyme cofactors serving a wide range of chemical functions. Coenzyme A is synthesized from pantothenic acid and ATP.


Rapid Study Kit for "Title":
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"Title" Tutorial Summary :

Nucleotides play a variety of important roles in all cells. They are the activated precursors of DNA and RNA. ATP, an adenine nucleotide, is a universal currency of energy in biological systems. GTP is an essential carrier of chemical energy. Adenine nucleotides are components of the coenzymes NAD+, NADP+, FMN, FAD and Coenzyme A. IMP is synthesized from ribose 5-phosphate. There are 11 reactions in the formation of IMP. Nucleoside monophosphates are converted to nucleoside diphosphates by base specific monophosphate kinases. Purine nucleotide synthesis is regulated by feedback inhibitor – AMP, GMP and IMP. Recycling of purines formed by the degradation of nucleotides is possible. Pyrimidine ring is synthesized as free pyrimidine and then it is incorporated into the nucleotide. Nucleotides of a cell undergo continuous turnover. Uric acid is the breakdown product of purine nucleotide. Gout is a disease characterized by elevated levels of uric acid in body fluids. Pyrimidines on degradation give rise to carbon dioxide, ammonia, β-alanine and β-amino isobutyrate.


Tutorial Features:
  • Concept map depicting nucleotide synthesis from purines/pyrimidines.
  • Structures are shown with examples and animated.
  • Tabulation of nitrogenous bases, nucleosides and nucleotides.
  • Formation of IMP is explicitly shown with animated structures.
  • Flow chart of various compounds like UMP is described.
  • Degradation of purines and pyrimidines is discussed in detail.

"Title" Topic List:

Nucleotide Metabolism

  • Introduction
  • Chemical structures of nucleotides

Synthesis of Purine Ribonucleotides

  • Synthesis of inosine monophosphate
  • Synthesis of adenine and guanine ribonucleotides
  • Regulation of purine nucleotide biosynthesis
  • Salvage pathway for purines

Synthesis of Pyrimidine Ribonucleotides

  • Synthesis of uridine monophosphate
  • Synthesis of UTP and CTP
  • Regulation of pyrimidine nucleotide biosynthesis

Formation of Deoxyribonucleotides

  • Production of deoxyribonucleotides
  • Synthesis of deoxythymidine monophosphate

Degradation of Nucleotides

  • Catabolism of purines
  • Fate of uric acid
  • Catabolism of pyrimidines

Nucleotide Coenzymes

  • Coenzymes
  • FAD and Coenzyme A


See all 24 lessons in college chemistry, including concept tutorials, problem drills and cheat sheets:
Teach Yourself Biochemistry Visually in 24 Hours

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