Structural Biochemistry/Nucleic Acid/Nucleotides

Nucleotides

Nucleotides consist of a base, sugar, and phosphate group. They are the building blocks of nucleic acids. Nucleotides are essential for the body for many reasons. They are needed for gene replication and transcription into RNA. They are also needed for energy. ATP, the body's form of energy, is a nucleotide with adenine as its base. Guanine nucleotides (GTP) are also a source of energy. Furthermore, derivatives of nucleotides are necessary in various biosynthetic processes. Nucleotides are necessary in signal transduction pathways as ewll.

The Biosynthesis of Nucleotides

There are two kinds of pathways in the biosynthesis of nucleotides: de novo and salvage. The following table contains similarities and differences between the two pathways.

De Novo	Similarities	Salvage
Simpler compounds are used in the synthesis of nucleotides. Numerous small pathways are repeated to assemble different nucleotides.	Both synthesize nucleotides, though they utilize different mechanisms.	Bases are preformed, recovered, and reconnected to a ribose.
Synthesizes pyrimidine nucleotides. Bicarbonate, aspartate, and glutamine are used to synthesize the ring of the pyrimidine. The ring then links with ribose phosphate, forming the nucleotide.	Both assemble ribonucleotides, which are then used to synthezise deoxyribonucleotides for DNA.	Synthesizes purine nucleotides. Various precurosrs may be used to form the purine ring, which is then added to ribose and phosphate.

Feedback inhibition regulates multiple steps in the biosynthesis of nucleotides. Examples of this include activation and inactivation of aspartate transcarbamoylase in the synthesis of pyrimidines by CTP and ATP respectively, and activation and inactivation of glutamine-PRPP amidotransferase by purine nucelotides.

Reduction of Ribonucleotides to Deoxyribonucleotides

Ribonucleotide reductase is a catalyst in reducing ribonucleoside diphosphates to deoxyribonucleotides. In this process, electrons flow from NADPH to sulfhydryl groups at ribonucleotide reductase's active sites. The reaction is summarized as follows:

1. An electron is transferred from cysteine on R1 to tyrosyl on R2. This creates a cysteine thiyl radical on R1, which is highly reactive on the active site.

2.A hydrogen from C3 of the ribose is then abstracted. This creates carbon radical.

3. The C3 radical helps release OH^- at carbon-2. This departs as H₂O after protonation from the second cysteine residue.

4. A third cysteine residue then provides a hydride to complete the reduction at C2. This returns the C3 to a radicala nd also generates a disulfide bond.

5. The c3 radical reacts with the original hydrogen that the first cysteine had extracted. A deoxyribonucleotide has now been generated and can leave the enzyme ribonucleotide reductase.

So What?

The biosynthesis and metabolism of nucleotides are important to the body because disruptions in them can result in pathology. If nucleotides are not degraded properly, certain conditions may arise. An example of this is gout. Urates are degraded proteins, and gout is when they are accumulated, generating poor joints and arthritis.

Similarly, if nucleotides are not synthesize properly, or if not enough are synthesized, conditions will arise as well. An example of this is the Lesch-Nyhan syndrome. Symptoms of this include mental deficiency, self-mutilation, and gout. This disease is due to a lack of an enzyme that is needed to synthesize purine nucleotides through the salvage pathway.

Source: Berg, Jeremy and Stryer, Lubert. Biochemistry: Fifth Edition. United States of America: W.H. Freeman and Company, 2002.