The below mentioned article provides a quick note on Nucleotides:- 1. Definition of Nucleotides 2. Biological Importance of Nucleotides 3. Structure 4. Nucleosides.
Definition of Nucleotides:
These are the compounds constituted by purine or pyrimidine bases, ribose or deoxyribose sugars and phosphoric acid.
Biological Importance of Nucleotides:
1. The nucleotides are important intracellular molecules of low molecular weight.
2. They play an important role in carbohydrate, fat and protein metabolism.
3. The best role of purine and pyrimidine nucleotides is to serve as the monomeric precursors of RNA and DNA.
4. The purine nucleotides also act as the high energy source ATP, cyclic AMP [cAMP] in a wide variety of tissues and organisms and as components of coenzymes FAD, NAD, NADP and of an important methyl donor, s-adenosylmethionine.
5. The pyrimidine nucleotides also act as high energy intermediates such as UDP- glucose and UDP-galactose in carbohydrate metabolism and CDP-acylglycerol in lipid synthesis.
Structure of Nucleotides:
The structures of purine and pyrimidine bases are given below. The direction of the numbering of the purine ring is different from that of the pyrimidine ring. But the number 5 carbon is the same in both.
Pyrimidine bases:
1. Cytosine (2-oxy-4-amino-pyrimidine)
2. Thymine (2, 4-di-oxy-5-methyl-pyrimidine)
3. Uracil (2, 4-di-oxy-pyrimidine)
Purine bases:
1. Adenine (6-amino-purine)
2. Guanine (2-amino-6-oxy-purine)
These are the two major purines found in living organisms. Two other purine bases (Hypoxanthine and Xanthine) also occur as intermediates in the metabolism of adenine and guanine.
Because of their resonant structures, they can exist in a lactim or lactam form. The lactam form is the predominant tautomer of uracil or thymine under physiologic condition. In plants, a series of purine bases containing methyl substituents occurs. Many have pharmacologic properties.
Examples are:
Coffee which contains caffeine (1,3,7- trimethyl xanthine).
Tea which contains theophylline (1, 3- di-methyl-xanthine).
Cocoa which contains Theo bromine (3, 7- di-methyl-xanthine).
In natural materials, many minor bases occur. Some of these unusual substituted bases are found only in the nucleic acids of bacteria and viruses. 5-methyl-cytosine and 5-hydroxymethyl-cytosine are significant components of bacteria and bacteriophage, respectively. More recently, N6-methyl-adenine, N6-dime- thyladenine and N7-methyl-guanine have been found in the nucleic acids of mammalian cells.
Nucleosides and Nucleotides:
The free bases occurring in nature are less in abundance than are their nucleosides and nucleotides.
A nucleoside is composed of a purine or a pyrimidine base and a ribose or a deoxyribose sugar.
The composition of some nucleosides is given:
The anti-form is necessary for the proper positioning of the complementary purine and pyrimidine bases in the double-stranded form of deoxyribonucleic acid. The structures of syn and anti-configurations of adenosine are given Fig. 7.8.
Nucleotides are the nucleosides phosphorylated on one or more of the hydroxyl groups of the sugar. Thus,
Adenosine monophosphate (AMP or Adenylate) = Adenine + ribose + phosphate
2-deoxyadenosine monophosphate (dAMP or deoxyadenylate) = Adenine + 2-deoxyribose + phosphate.
Thymidylic acid (TMP) = Thymine + 2-deoxyribose + phosphate.
Uridylic acid (UMP) = Uracil + ribose + phosphate.
Synthetic Nucleosides and Nucleotides:
Synthetic nucleobases, nucleosides and nucleotides are widely used in the medical sciences and clinical medicine. The pharmacologic view is that either the heterocyclic ring structure or the sugar moiety is changed in such a way as to induce toxic effects when they are incorporated into various cellular constituents resulting in the inhibition of enzyme activities.
6-thioguanine and 6-mercaptopurine, in which the hydroxyl groups are replaced with thiol groups at the 6 position are widely used clinically.
4-hydroxypyrazole pyrimidine (allopurinol) is marketed as an inhibitor of xanthine oxidase. Hence, it is used for the treatment of hyperuricemia and gout.
Cytarabine (arabinosyl cytosine) and vidarabine (arabinosyl adenine) are used in the chemotherapy of cancer and viral infections.
Azathioprine is useful in organ transplantation.
More recently, both aminophylline and theophylline are used clinically to inhibit the catabolism of intracellular cAMP.