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Nucleotides build your genes, fuel your cells and even boost umami

The same molecules that string together into DNA and RNA also power nearly everything a cell does. ATP, a nucleotide carrying three phosphates, funds protein building, movement and cell division. Others relay signals or help enzymes work, and a few, added as yeast extract, deepen the savoury umami flavour of processed food.

Each nucleotide has three parts: a nitrogen-containing base, a five-carbon sugar and a phosphate group of one to three phosphates. The base and sugar alone make a nucleoside. With ribose the result is a ribonucleotide, and with deoxyribose a deoxyribonucleotide. Chained together, phosphates bridge the sugars of neighbouring units into a backbone that always runs from the so-called 5-prime end to the 3-prime end, and in a double helix the two strands point opposite ways.

Outside the genome, nucleotides are workhorses. Triphosphates such as ATP and GTP deliver chemical energy across the cell. Cyclic forms, in which one phosphate binds the sugar at two points, act as messengers, among them cAMP and cGMP. Nucleotides also sit at the heart of cofactors like coenzyme A, NAD and FAD, which shuttle electrons in metabolic reactions, and they donate phosphate groups that switch proteins on or off.

Bodies get nucleotides from food and also make them, mostly in the liver, either from scratch or by recycling pieces through salvage pathways. Raw materials come from carbohydrate and amino acid metabolism, plus ammonia and carbon dioxide. The two families are built differently. Pyrimidines are assembled as a free ring, orotic acid, before being attached to an activated sugar. Purines are constructed directly on the sugar, through a ten-step pathway ending in IMP, which is then converted in two further steps to either AMP or GMP.

Breakdown differs as well. Human cells can dismantle pyrimidine rings completely into carbon dioxide and ammonia. Purine rings cannot be fully broken apart; they end up as inert uric acid that the body excretes, although guanine and IMP can be salvaged for reuse. In laboratories, protected building blocks allow chemists to assemble custom strands and analogues found nowhere in nature.

Source: Nucleotide

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