Uracil

In RNA, uracil base-pairs with adenine and replaces thymine during DNA transcription. Methylation of uracil produces thymine. In DNA, the evolutionary substitution of thymine for uracil may have increased DNA stability and improved the efficiency of DNA replication (discussed below). Uracil pairs with adenine through hydrogen bonding. When base pairing with adenine, uracil acts as both a hydrogen bond acceptor and a hydrogen bond donor. In RNA, uracil binds with a ribose sugar to form the ribonucleoside uridine. When a phosphate attaches to uridine, uridine 5′-monophosphate is produced. Uracil undergoes amide-imidic acid tautomeric shifts because any nuclear instability the molecule may have from the lack of formal aromaticity is compensated by the cyclic-amidic stability. The negative charge is placed on the oxygen anion and produces a pKa of less than or equal to 12. The basic pKa = −3.4, while the acidic pKa = 9.389. In the gas phase, uracil has four sites that are more acidic than water. In DNA Uracil is rarely found in DNA, and this may have been an evolutionary change to increase genetic stability. This is because cytosine can deaminate spontaneously to produce uracil through hydrolytic deamination. Therefore, if there were an organism that used uracil in its DNA, the deamination of cytosine (which undergoes base pairing with guanine) would lead to formation of uracil (which would base pair with adenine) during DNA synthesis. Uracil-DNA glycosylase excises uracil bases from double-stranded DNA. This enzyme would therefore recognize and cut out both types of uracil – the one incorporated naturally, and the one formed due to cytosine deamination, which would trigger unnecessary and inappropriate repair processes. This problem is believed to have been solved in terms of evolution, that is by "tagging" (methylating) uracil. Methylated uracil is identical to thymine. Hence the hypothesis that, over time, thymine became standard in DNA instead of uracil. So cells continue to use uracil in RNA, and not in DNA, because RNA is shorter-lived than DNA, and any potential uracil-related errors do not lead to lasting damage. Apparently, either there was no evolutionary pressure to replace uracil in RNA with the more complex thymine, or uracil has some chemical property that is useful in RNA, which thymine lacks. Uracil-containing DNA still exists, for example in: • DNA of several phages • Endopterygote development • Hypermutations during the synthesis of vertebrate antibodies. ==Synthesis==

Biological Organisms synthesize uracil, in the form of uridine monophosphate (UMP), by decarboxylating orotidine 5'-monophosphate (orotidylic acid). In humans this decarboxylation is achieved by the enzyme UMP synthase. In contrast to the purine nucleotides, the pyrimidine ring (orotidylic acid) that leads uracil is synthesized first and then linked to ribose phosphate, forming UMP. Laboratory There are many laboratory synthesis of uracil available. The first reaction is the simplest of the syntheses, by adding water to cytosine to produce uracil and ammonia: Prebiotic In 2009, NASA scientists reported having produced uracil from pyrimidine and water ice by exposing it to ultraviolet light under space-like conditions. This suggests a possible natural original source for uracil. In 2014, NASA scientists reported that additional complex DNA and RNA organic compounds of life, including uracil, cytosine and thymine, have been formed in the laboratory under outer space conditions, starting with ice, pyrimidine, ammonia, and methanol, which are compounds found in astrophysical environments. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), a carbon-rich chemical found in the Universe, may have been formed in red giants or in interstellar dust and gas clouds. Based on 12C/13C isotopic ratios of organic compounds found in the Murchison meteorite, it is believed that uracil, xanthine, and related molecules can also be formed extraterrestrially. Data from the Cassini mission, orbiting in the Saturn system, suggests that uracil is present on the surface of the moon Titan. In 2023, uracil was observed in a sample from 162173 Ryugu, a near-Earth asteroid, with no exposure to Earth's biosphere, giving further evidence for synthesis in space. ==Reactions==

Uracil readily undergoes regular reactions including oxidation, nitration, and alkylation. While in the presence of phenol (PhOH) and sodium hypochlorite (NaOCl), uracil can be visualized in ultraviolet light. Uracil also has the capability to react with elemental halogens because of the presence of more than one strongly electron donating group. ==Uses==

Uracil's use in the body is to help carry out the synthesis of many enzymes necessary for cell function through bonding with riboses and phosphates. Uracil is important for the detoxification of many carcinogens, for instance those found in tobacco smoke. Uracil is also required to detoxify many drugs such as cannabinoids (THC) and morphine (opioids). It can also slightly increase the risk for cancer in unusual cases in which the body is extremely deficient in folate. Uracil can be used for drug delivery and as a pharmaceutical. When elemental fluorine reacts with uracil, they produce 5-fluorouracil. 5-Fluorouracil is an anticancer drug (antimetabolite) used to masquerade as uracil during the nucleic acid replication process. Uracil has also shown potential as a HIV viral capsid inhibitor. Uracil derivatives have antiviral, anti-tubercular and anti-leishmanial activity. Uracil can be used to determine microbial contamination of tomatoes. The presence of uracil indicates lactic acid bacteria contamination of the fruit. Uracil derivatives containing a diazine ring are used in pesticides. Uracil derivatives can enhance the activity of antimicrobial polysaccharides such as chitosan. In yeast, uracil concentrations are inversely proportional to uracil permease. Mixtures containing uracil are also commonly used to test reversed-phase HPLC columns. As uracil is essentially unretained by the non-polar stationary phase, this can be used to determine the dwell time (and subsequently dwell volume, given a known flow rate) of the system. == References ==