1. Nucleic Acids, Unit 5

Nucleic Acids

Finally, the last unit!!

Nucleic Acids are the fourth class of macromolecules besides Proteins, Lipids, and Carbohydrates. They’re composed of blocks called nucleotides, which are made up of a sugar, a base, and a phosphate group(s).

Some uses/examples of nucleic acids:

  • DNA and RNA
  • ATP: Energy currency in cells
  • Precursors of UEA like NAD+
  • Signaling acids like cyclic AMP

Pentoses are the sugars found in nucleic acids.

  • RNA contains Ribose
  • DNA contains Deoxyribose
  • The carbon numbering of sugars in the context of nucleic acids uses a prime (‘) notation: the 5’-carbon, for example

They differ by the group attached to the 2′-C: hydroxyl (OH) in Ribose and H in Deoxyribose.

Fg10_09b_revised

Purines and Pyrimidines

Various nitrogen-containing molecules serve as bases in nucleotides: purines (Adenine and Guanine) with a double-ring structure and pyrimidines (Cytosine, Uracil, Thymine) with a single ring structure. Both are hydrophobic and aromatic.

Purine Examples

Purines

Note that purines have two rings, an imidazole joined to a pyrimidine

Pyrimidine Examples

Pyrimidines
Pyrimidines

Notes:

  • Adenine, Cytosine, and Guanine are found in both RNA and DNA
  • Uracil is unique to RNA
  • Thyamine is unique to DNA

The 1-C of the pentose sugar is covalently bonded to a nitrogenous base to form a nucleoside.

A nucleoside is a base and a sugar

 

A nucleotide is formed by the covalent linkage of 1, 2, or 3 phosphates to a nucleoside–to the 5-C of a pentose. For example, ATP is composed of three phosphates attached to adenosine, which is a nucleoside.

  • Purine nucleosides/tides end in -osine.
  • Pyrimidine nucleosides/tides end in -idine.

For example, Adenosine monophosphate, a purine nucleoside

adenosine monophosphate

 

1000px-Nucleotides_1.svg

 

Nucleic Acids are assembled by the covalent linkage of nucleotides.

There are two classes of nucleotides, Ribonucleotide (contain ribose and are found in RNA) and Deoxyribonucleotide (contain deoxyribose, found in DNA). The identity of “ribo” or “deoxyribo” are determined by the type of base attached to the pentose. So four of each.

In nucleotide from both, the 5-C of the pentose binds phosphate groups. The 3-C of the pentose carries a hydroxyl group.

0322_DNA_Nucleotides

In a nucleic acids, the nucleotides are bound together by phosphodiester linkages. These linkages are formed when the 5′ phosphate of the nucleotide binds reacts with the 3′-hydroxyl of another nucleotide. During nucleic acid polymerization, the 5′-phosphate of an incoming nucleotide with the free 3′-hydroxyl of the growing nucleotide chain.

The direction is fixed. The nucleic acids are said to have a 5′ to a 3′ polarity.

Most DNA molecules are made of two anti-parallel strands making the characteristic DNA double helix. The sugar-phosphate portion of the strands form the external backbone of the helix. The bases are at the center. Bases of one strand form hydrogen bonds with bases of the other. Each base pair contains a purine and a pyrimidine.

  • A pairs with T
  • C pairs with G

The stability of the double helix is due to “interstrands,” hydrogen bonds, and to intrastrand van der Waal forces between base pairs that are stacked on top of each.

The purine-pyrimidine base pair optimizes the number of hydrogen bonds between bases as well as the alignment of the three atoms forming the hydrogen bond. These alignments strengthen the hydrogen bonds too. All together, it explains why the diameter of the double helix is constant: equal spacing between two sugar/phosphate backbones of opposite strands wouldn’t be maintained if like pentoses were to bound.

Most RNA molecules are single stranded. But base pairing is also important here too. They can form secondary structures by base pairing and can fold into more complex structures. These are important for RNA to maintain protein interaction or for the catalytic activities of some RNA known as ribosomes.

The Production of Nucleotides

Nucleotides are produced by two distinct pathways.

  1. Salvage Pathway (“reusing existing bases”), a recycling pathway
    PRPP + base —> NMP + PPi
    PRPP + adenine —> AMP + PPi
  2. De novo synthesis (“new synthesis”)
    PRPP + amino acids + HCO3- + folate + …. —> nucleotide
    Nucleotides are formed from scratch

PRPP: derived from G6P via the Pentose Phosphate Pathway. PRPP contain the ribose and phosphate groups that are incorporated into the ribonucleotides in both the Salvage and De novo pathway.

Other uses of nucleotides (besides DNA and RNA)

There’s ATP, of course. That’s a big one. It’s a building block for the UEAs: FAD, NAD+, and NADP+.

NAD+ is used in catabolic processes while NADP+ is used in anabolic processes.

Coenzyme-A and NAD+ also both use AMP as a building block.

UTP for Glycogen synthesis

CTP for fatty-acid synthesis