Nucleotides Structure

Nucleotides Structure

Dr. Samah Hamad
MBBS, MSc
MD YR -1
16 th. April. 2025

Organic Compounds

  • Proteins

  • Nucleic Acids

  • Lipids

  • Carbohydrates

The Genome

  • Most genomes, including the human genome and those of all other cellular life forms, are made of DNA (deoxyribonucleic acid) but a few viruses (HIV) have RNA (ribonucleic acid) genomes.

  • DNA and RNA are polymeric molecules made up of chains of monomeric subunits called nucleotides.

The Human Genome

  • The human genome, which is typical of the genomes of all multicellular animals, consists of two distinct parts:

    • The nuclear genome

    • The mitochondrial genome

Human Cell

  • Illustration of a human cell, showing the nuclear genome and mitochondrial genomes.

Nucleotides

  • The building blocks of nucleic acids are Nucleotides.

  • A nucleotide has three parts:

    • A sugar

    • A phosphate group

    • A nitrogen base

Nitrogenous Base

  • Refers to the nitrogenous base component of a nucleotide.

Purines and Pyrimidines

  • Purines and pyrimidines are heterocyclic structures containing in addition to carbon other atoms such as nitrogen.

Pyrimidines and Purines Structures

  • Illustrations of pyrimidine and purine structures with labeled atoms.

Pyrimidine Bases

  • An aromatic nitrogen base-containing, a single six-membered ring.

  • Numbering is clockwise from 1-6.

Pyrimidine Bases Physiochemical Properties

  • Water-soluble at physiological pH.

  • Capable of forming hydrogen bonds.

  • Absorbing the light at a wavelength of 290nm290 nm, this is used for estimating the pyrimidine concentration.

Uracil (U)

  • 2-4 DI OXY PYRIMIDINE

  • Chemical structure of Uracil.

Thymine (T)

  • (5-methyluracil)

  • 2,4-DI OXY-5-METHYL PYRIMIDINE

  • Chemical structure of Thymine.

Cytosine (C)

  • 2- OXY -4- AMINO PYRIMIDINE

  • Chemical structure of Cytosine.

Pyrimidine Bases in DNA and RNA

  • The pyrimidines in DNA are cytosine (C) and thymine (T).

  • The pyrimidines in RNA are cytosine (C) and uracil (U).

  • Cytosine can be found in DNA and RNA.

  • Thymine is found only in DNA, while uracils are found only in RNA.

Purines

  • Purines consist of linked five-membered and six-membered rings.

  • Formed by fusion of pyrimidine with the imidazole ring.

  • Numbering is anticlockwise (1-9).

Purines Structures

  • 6-amino purine - Adenine (A)

  • 2-amino,6-oxy purine - Guanine (G)

  • Chemical structures of Adenine and Guanine.

Purines Physiochemical Properties

  • Water-soluble at physiological pH.

  • Capable of forming hydrogen bonds.

  • Absorbing the light at a wavelength of 290nm290 nm, this is used for quantitation and detection of purines.

  • Guanine present as keto or enol form but keto form predominates at physiological pH.

Purines and Pyrimidines

  • Summary table showing the structures of Adenine, Cytosine, Guanine, Thymine, and Uracil, indicating their presence in DNA and/or RNA.

Minor Bases or N-Base Derivatives

  • Introduction to minor or modified nitrogenous bases.

Purines Other Purine Bases

  • Other purine bases produced during metabolism, present in a free state in cells:

    1. Hypoxanthine.

    2. Xanthine.

    3. Uric acid (end product of Adenine & Guanine catabolism)

Modified Pyrimidine Bases

  • A few other modified pyrimidine bases like dihydrouracil and 5-methyl cytosine are also found rarely in some types of RNA.

  • Structures of 5-methyl cytosine and Dihydro-uracil.

Uridine Nucleotides (UMP)

  • Uridylic acid and Pseudo uridylic acid.

  • In pseudouridylic acid (found in tRNA) uridine is attached to ribose phosphate in a C-C bond instead of a C-N bond in UMP.

N Bases Derivatives

  • 5-methylcytosine of bacterial and human DNA, 5-hydroxymethylcytosine of bacterial and viral nucleic acids, and mono- and the di-N-methylated adenine and guanine of mammalian messenger RNAs that function in oligonucleotide recognition and in regulating the half-lives of RNAs.

  • Methylated heterocycles of plants include the xanthine derivatives caffeine of coffee, theophylline of tea, and theobromine of cocoa.

Nucleosides and Nucleotides

  • Nucleoside: Consist of ribose sugar or 2’- deoxy ribose linked covalently via N-glycosidic bond to N-9 of purine or to N-1 of a pyrimidine.

  • C-1 carbon atom of ribose or deoxyribose is bonded to N-1of pyrimidine or to N-9 of purine.

Nucleosides Structures

  • Adenosine and Guanosine structures.

Nucleosides Structures

  • Uridine and Cytidine structures.

Purine and Pyrimidine Nucleosides

  • List of purine and pyrimidine nucleosides with ribose and deoxyribose sugars.

Nucleosides Structures

  • Structures of Adenosine, Cytidine, Guanosine and Uridine.

Nucleotides

  • Nucleosides are found in the cell primarily in their phosphorylated form.

  • These are termed nucleotides.

  • Nucleotide = Base + sugar + P

  • The most common site of phosphorylation of nucleotides found in cells is the hydroxyl group attached to the 5’-carbon of the ribose.

  • The bond is a phosphoester bond.

  • Nucleotides can exist in the mono-, di-, or tri- phosphorylated forms.

Adenylic acid (AMP) and 2'-deoxyadenylic acid (dAMP)

  • Structures of AMP and dAMP.

Purine and Pyrimidine Nucleotides

  • List of purine and pyrimidine nucleotides with ribose and deoxyribose sugars.

Nucleotides

  • The 3′- and 5′-nucleotides are nucleosides with a phosphoryl group on the 3′- or 5′-hydroxyl group of the sugar, respectively.

  • Most nucleotides are 5′-: Additional phosphoryl groups, ligated by acid anhydride bonds to the phosphoryl group of a mononucleotide, form nucleoside diphosphates and triphosphates.

Mono, Di and tri phosphate

  • Structure of ATP showing anhydride and ester bonds.

Nucleotide Functions

  • Nucleotides are required for numerous functions within the cell:

    1. Precursors of the nucleic acids DNA and RNA.

    2. ATP is a universal currency of energy in biological systems.

    3. Phosphate transfer reactions (ATP) e.g. Glucose + ATP -> phosphoglucose.

Nucleotide Functions (Cont.)

  • Serving as mediators of numerous important cellular processes: Second messengers in signal transduction events e.g. cyclic-AMP (cAMP), cyclic-GMP (cGMP).

cAMP, cGMP

  • cAMP and cGMP as second messengers and their functions.

    • cAMP acts as a second messenger for calcitonin, corticotrophin, epinephrine, FSH, TSH, LH, MSH, etc.

    • It enhances glycogenolysis and lipolysis.

    • Increases acid secretion from gastric mucosa.

    • Dispersion of melanin pigment.

    • Aggregation of platelets.

    • cGMP serves as a second messenger in response to nitric oxide (NO) during relaxation of smooth muscle.

Nucleotide Functions (Cont…)

  • Controlling numerous enzymatic reactions e.g. glycolysis PFK-1 by AMP.

  • AMP activates phosphorylase b induce glycogen breakdown.

  • Serving as activated intermediates in numerous biosynthetic reactions e.g: UDP-glucose, UDP-galactose in CHO biosynthesis and CDP – Di-acylglycerol in lipid biosynthesis.

Uridine Nucleotides (UMP)

  • UMP is obtained by the hydrolysis of RNAase and Phosphodiesterase.

  • UDP-sugar derivatives participate in sugar epimerizations and in the biosynthesis of glycogen, glucosyl disaccharides, and the oligosaccharides of glycoproteins and proteoglycans.

  • UDP-glucuronic acid forms the urinary glucuronide conjugates of bilirubin and of many drugs, including aspirin.

Cytidine Nucleotides

  • CDP-choline, CDP-glycerol, and CDP ethanolamine are involved in the biosynthesis of phospholipids.

  • CMP-acetyl neuraminic acid is an important precursor of cell-wall polysaccharides in bacteria.

Nucleotide Functions (Cont.)

  • Forming a portion of several Coenzymes: NAD, NADP, FAD, CoA, and S-adenosylmethionine

  • Structure of NAD+ and Coenzyme A.

Synthetic Nucleotide Analogs

  • Inhibition of enzymes essential for nucleic acid synthesis or their incorporation into nucleic acids with resulting disruption of base pairing.

  • Oncologists employ 5-fluoro- or 5-iodouracil, 3-deoxyuridine, 6-thioguanine and 6-mercaptopurine, 5- or 6-azauridine, 5- or 6-azacytidine, and 8-azaguanine), which are incorporated into DNA prior to cell division.

Synthetic Nucleotide Analogs (Cont…)

  • The purine analog allopurinol, used in the treatment of hyperuricemia and gout.

  • Cytarabine (arabinose replaces ribose) is used in the chemotherapy of cancer.

  • Azathioprine, which is catabolized to 6-mercaptopurine, is employed during organ transplantation to suppress immunologic rejection.

  • Aminophylline and theophylline increase cAMP level relief asthma.

  • Acyclovir guanosine with incomplete ribose for herpes simplex.

Nucleoside Analogs

  • Nucleoside analogs containing modified bases or sugars are used as anti-cancer agents, anti-viral agents, and mutagens.

  • Structures of 5-Iodo-2'-deoxyuridine, 5-Fluorouracil, 6-Thioguanine, Alloburinol, 6-Mercaptopurine, 6-Azauridine and 8-Azaguanine.

Nucleoside Analogues as Drugs

  • Table listing nucleoside analogues, their corresponding drugs, and their uses.

    • Deoxyadenosine analogues: Didanosine, Vidarabine; Uses: HIV, Chemotherapy

    • Deoxycytidine analogues: Cytarabine, Emtricitabine, Lamivudine, Zakcitabine; Uses: Chemotherapy, HIV, Hepatitis B

    • Deoxyguanosine analogues: Abacavir, Entecavir; Uses: HIV, Hepatitis B

    • Deoxy-thymidine analogues: Stavudine, Telbivudine, Zidovudine; Uses: HIV, Hepatitis B

    • Deoxyuridine analogues: Idoxuridine, Trifluridine; Uses: HIV

Thank You

  • Final slide thanking the audience. This marks the end of the presentation.