Nucleic acid metabolism

Nucleic acids are polymers (so-called "biopolymers") made up of a variety of monomers called nucleotides.

Nucleotide synthesis is an anabolic mechanism generally involving the chemical reaction of phosphate, pentose sugar, and a nitrogenous base.

In the more complex multicellular animals, they are both primarily produced in the liver but the two different groups are synthesized in different ways.

[1] Lesch–Nyhan syndrome is caused by a deficiency in hypoxanthine-guanine phosphoribosyltransferase or HGPRT, the enzyme that catalyzes the reversible reaction of producing guanine from GMP.

This is a sex-linked congenital defect that causes overproduction of uric acid along with mental retardation, spasticity, and an urge to self-mutilate.

Unlike in purine synthesis, the sugar/phosphate group from PRPP is not added to the nitrogenous base until towards the end of the process.

Purine and pyrimidine nucleosides can either be degraded to waste products and excreted or can be salvaged as nucleotide components.

[5] Cytosine and uracil are converted into beta-alanine and later to malonyl-CoA which is needed for fatty acid synthesis, among other things.

The leftover carbon skeletons such as acetyl-CoA and Succinyl-CoA can then be oxidized by the citric acid cycle.

Pyrimidine degradation ultimately ends in the formation of ammonium, water, and carbon dioxide.

Defects in purine catabolism can result in a variety of diseases including gout, which stems from an accumulation of uric acid crystals in various joints, and adenosine deaminase deficiency, which causes immunodeficiency.

[10][11][12] Once the nucleotides are synthesized they can exchange phosphates among one another in order to create mono-, di-, and tri-phosphate molecules.

The conversion of a nucleoside-diphosphate (NDP) to a nucleoside-triphosphate (NTP) is catalyzed by nucleoside diphosphate kinase, which uses ATP as the phosphate donor.