Purine- Structure, Types, Derivatives, Modification, Effects

Purine is a water-soluble heterocyclic aromatic organic compound consisting of a six-membered pyrimidine ring and a five-membered imidazole ring.

A nucleotide sequence in the cell’s DNA determines the nucleotide sequence of each RNA and the amino acid sequence of each protein.

Nucleotides have three characteristic components:

  1. A nitrogenous (nitrogen-containing) base
  2. A pentose
  3. A phosphate

The nitrogenous bases are derivatives of two parent compounds, pyrimidine, and purine.

Purine Structure

  • Nine atoms make up the basic purine structure.
  • A six-membered pyrimidine ring and a five-membered imidazole ring fused to make up the two cycles of purine.
  • Four nitrogen atoms exist in positions 1, 3, 7, and 9.
  • The first nitrogen of the six-membered ring serves as the starting point for purine’s numbering, which moves counterclockwise.
  • The imidazole ring is numbered in a clockwise direction.
  • Purine bases are attached with 1’ carbon of pentoses through the ninth nitrogen atom to form nucleosides.
  • Significant delocalization exists among the purine ring’s electrons.
  • Positions 3 and 7 are electron-rich and susceptible to electrophilic attack, while positions 2, 6, and 8 are susceptible to nucleophilic attack.
Purine- adenine and guanine
Purine- adenine and guanine

Types of Purine

The primary purines are adenine and guanine in both RNA and DNA.

Adenine

Molecular formula: C5H5N5

Molecular weight: 135.13 dalton

Melting point: 360-365°C

Solubility: 1030 mg/L (at 25 °C)

  • It is a white, crystalline purine base with an amine group linked to the carbon at position 6 that is present in both RNA and DNA.
  • Thymine in DNA and Uracil in RNA is complementary to adenine.
  • The amine group at position 6 and the additional double bond between N-1 and C-6 in the heterocyclic aromatic (pyrimidine) ring distinguish adenine from guanine.
  • The energy-rich adenosine triphosphate (ATP) and the cofactors flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), and coenzyme A are examples of adenine derivatives that play various roles in biochemistry, including cellular respiration.

Guanine

Molecular formula: C5H5ON5

Molecular weight: 151.13 dalton

Melting point: 360°C

Solubility: 2080 mg/L (at 37 °C)

  • It is a white, insoluble, crystalline material.
  • It is a 2-aminopurine with a 6-oxo substituent in both RNA and DNA. 
  • Guanine is complementary to Cytosine in both DNA and RNA.
  • It was first isolated from guano (bird manure), hence the name. 
  • Ammonia, a byproduct of protein breakdown in cells, is converted to guanine by spiders, scorpions, and a few other amphibians, as it can be eliminated with minimal water loss.

Purine Derivatives

Aside from adenine and guanine, other significant metabolites include hypoxanthine, xanthine, theophylline, theobromine, caffeine, uric acid, and isoguanine.

Purine Derivatives
Purine Derivatives
  • 3, 7-dimethylxanthine (theobromine) is a powerful diuretic and facilitates oral administration by forming soluble complexes with salts of different organic acids and also in treating asthma.
  • The primary purine found in coffee beans and tea leaves is 1,2,7-trimethylxanthine (caffeine) which is a cardiac and respiratory stimulant and is frequently used in headache powders. 
  • The main purine component of human urine is 1-methylxanthine.
  • 3- and 7-Methylpurines are also minor components of urine, particularly after consuming substantial amounts of caffeine or other methylated xanthines. 
  • Paraxanthine, also known as 1,7-Dimethylxanthine, is an effective diuretic with antithyroid effects.

Purine Modification

  • Numerous biologically active substances have been produced from modified purine structures, both of natural and synthetic origin.
  • These substances often include simple alterations to known purines, such as cytokinins, 6-N-alkylated adenines, or structural changes to the carbohydrate moiety of ribose or deoxyribose derivatives, as with arabinosides.
  • Methylation is the most common form of purine modification.
  • Some modified purines can be found in transfer RNAs (tRNAs).
  • Before the reverse shift to the B-supercoiled conformation, methylation of one of the two purines is presumably eliminated during the cell cycle.
  • Methylation of purines (particularly of adenine) in DNA is known to occur in the genetic material of microorganisms. The 6-methyladenine is found in bacterial DNA.

Antibiotics and Related Compounds

Numerous glycosylpurines that have been extracted from microbes have shown significant biological activity.

  • 9-(Darabinofuranosyl) adenine, often known as Ara A, is a potent antiviral and anticancer drug.
  • Both bacterial and human cells have been thoroughly examined to determine the effects of puromycin as a protein production inhibitor. However, its use as an antibiotic is constrained by the fact that it is highly toxic to mammals.
  • The ketosylpurines (psicofuranine and decoyinine) work by inhibiting XMP aminase exhibiting antibacterial efficacy and against adenocarcinoma in rats.
  • Septacidin has some activity against tumor cells.
  • Nebularine is known to show antibacterial properties.
  • 6-Mercaptopurine (6-thioxo-l,6-dihydropurine) was among the first purine derivatives used in leukemia treatment, particularly in children.
  • 2,6-diaminopurineare has anti-leukemic activity.

Purine Health Effects

  1. Uric acid is the metabolic end product of purine metabolism. 
  2. Too much purine in the body can result in hyperuricemia, a condition when there is an excessive amount of uric acid in the blood.
  3. A higher risk of developing diabetes is associated with high uric acid levels in the body.
  4. High uric acid levels in the body are also known to cause the formation of uric acid crystals leading to gout (inflammation in the joint) and kidney stones.

References

  1. Dvir G., Benjamin A., Palmer B.A., Weiner S., & Addadi L. (2017). Light manipulation by guanine crystals in organisms: biogenic scatterers, mirrors, multilayer reflectors and photonic crystals. Advanced Functional Materials. 27 (6): 1603514. https://doi.org/10.1002/adfm.201603514
  2. Jain J.L., Jain S. & Jain N. (2005). Nucleic Acids. In Fundamentals of Biochemistry. Multicolour Illustrative Edition. S. Chand & Company Ltd, pg. 284-286
  3. Kumari A. (2018). Purine de novo Synthesis. In Sweet Biochemistry. Academic Press, pg. 93-97. https://doi.org/10.1016/B978-0-12-814453-4.00018-2
  4. Maas R. (2004). Prereplicative purine methylation and postreplicative demethylation in each DNA duplication of the Escherichia coli replication cycle. The Journal of biological chemistry279(49), 51568–51573. https://doi.org/10.1074/jbc.M407394200
  5. Nelson D. L. & Cox M.M. (2008). Nucleotides and Nucleic Acids. In Lehninger Principles of Biochemistry. Fifth Edition. W.H. Freeman and Company, pg. 271-274. ISBN-I0: 0-7167-7r08-X
  6. PubChem. Purine. National Library of Medicine. National Institutes of Health. Department of Health and Human Services, USA. Accessed from: https://pubchem.ncbi.nlm.nih.gov/compound/Purine. Accessed on: 14.09.2022
  7. PubChem. Adenine. National Library of Medicine. National Institutes of Health. Department of Health and Human Services, USA. 
  8. Accessed from: https://pubchem.ncbi.nlm.nih.gov/compound/Adenine#section=Chemical-and-Physical-Properties. Accessed on: 14.09.2022
  9. PubChem. Guanine. National Library of Medicine. National Institutes of Health. Department of Health and Human Services, USA. 
  10. Accessed from: https://pubchem.ncbi.nlm.nih.gov/compound/Guanine#section=Chemical-and-Physical-Properties. Accessed on: 14.09.2022
  11. Robert J., Ouellette J. & David Rawn. (2018). Nucleosides, Nucleotides, and Nucleic Acids. In Organic Chemistry (Second Edition). Academic Press, pg. 973-1000. https://doi.org/10.1016/B978-0-12-812838-1.50030-X.
  12. Shaw G. (1984). Purines. In Comprehensive Heterocyclic Chemistry. Pergamon. pg. 499-605. https://doi.org/10.1016/B978-008096519-2.00077-1
    WebMD. (2022). Foods High in Purines. Accessed from: https://www.webmd.com/diet/foods-high-in-purines#1. Accessed on: 14.09.2022

Leave a Comment