Originally published in: Encyclopedia of Food Microbiology, 1999
There are three different types of nucleotides: (1) nitrogenous base, (2) a five-carbon monosaccharide (aldopentose), and (3) phosphoric acid.
A nitrogenous base. .Diagram.Their chemical structure and the numbering of their elements are shown in Figure 6.1. .There is no atom that is not on the same plane as an atom of a purine or pyrimidine.
Fig. 6.1.Pyrimidine elements have a different number of atoms than purines.
Carbons 2 and 5 are the same in both cycles.
DNA consists of five different nucleotide bases.They consist of two purines and three pyrimidines.Thymine (5-methyl-2,4-dioxipyrimidine), cytosine (2-oxo-4-aminopyrimidine), and uracil (2,4-dioxoypyrimidine) are pyrimidine bases.
Figs contain pyrimidine and guanine bases.6.2 and 6.3 refer to the ketone and lactam forms of these nucleotides, which are predominant in natural products.These nucleotides are present in a much smaller proportion in the enol and lactim isomers.In order for these isomers to form, the hydrogen atom bound to the neighboring nitrogen must be displaced toward the oxygen.In the end, nucleic acids may contain a small amount of other bases derived from the principal bases, such as 5-methylcytosine.
Purine and pyrimidine bases absorb radiation in the ultraviolet (UV) region of the spectrum with a maximum at 260 nanometers.Nucleic acids can be identified in a sample and their concentrations estimated using this property.
The aldopentoses.DNA is composed of monosaccharides, such as d-ribose or d-2-deoxyribose.In view of the pentose, two types of nucleic acids are differentiated: ribonucleic acids (RNAs) and deoxyribonucleic acids (DNAs).(The pentoses and bases of aldopentoses in nucleic acids assume the furanose form, respectively.)
Diagram 6.4.Acids present in nucleic acids.
Ribose and deoxyribose are both linked by a *-glycosidic bond to nitrogen 9 or 1 of the purine or pyrimidine bases, which allows them to remain free of rotation.In chemistry, nucleosides are molecules made up of an nitrogenous base, pyrimidine or purine, and aldopentose.The position of the nitrogenous base and monosaccharide varies between the two main configurations shown in Figure 3.7.These correspond to the syn and anti configurations.(See figure 6.6).
Illustration of.NAD+ (Adenosine).
(A) Synchronic; (B) Antichronic.
Image 6.6.Nuclear thymidine.
A nucleotide is formed by esterifying ribose or deoxyribose with phosphoric acid from the hydroxyl group in carbon 5′ (Fig. 6.7).
This figure shows.guanylic acid (nucleotide, anti form).
Purine and Pyrimidine Metabolism
Thesis by Antonio Blanco and Gustavo Blanco, in Medical Biochemistry, 2017
In contrast, human beings produce their own nitrogenous bases, so they do not rely on purines or pyrimidines in their diet.
The purine ring is formed by the formation of residues from different sources during purine biosynthesis. .This molecular assembly is performed with the aid of ribose-5-P.To make PRPP, phosphoribosylpyrophosphate synthetase, an enzyme inhibited by the end products, AMP, GMP, and IMP, is involved in a reaction. Next, a nucleotide is generated.
The APRT and hypoxanthine-guanine phosphoribosyl transferases are needed for the sulfuryl salvage pathway.
As nucleic acids get degraded into nucleosides and nucleotides, urine catabolism begins.(Adenosine deaminase catalyzes the deamination of adenosine).This inosine is phosphorylated (mediated by nucleoside phosphorylase) to yield hypoxanthine and ribose-P.
Then, the hypoxanthine is oxidized to xanthine (catalyzed by xanthine oxidase).As part of the metabolism, guanosine is hydrolyzed to guanine and ribose.Deamination of guanine results in xanthine (via guanase).Xanthine, formed from adenine and guanine, is oxidized into uric acid by xanthine oxidase.
Uric acid is a byproduct of purine catabolism in humans.Poorly soluble, it most commonly passes through the urine.
In normal plasma, uric acid concentrations range from 4 to 6 mg/dL.Pathological conditions may cause this concentration to rise higher.
Gout is characterized by an elevated level of urate in the blood and urine.It causes arthritis and kidney stones.
Aspartate and carbamoyl phosphate are required for pyrididine biosynthesis.The carbamoyl phosphate is synthesized from glutamine and CO2 (with the assistance of CPS 2).As carbamoyl-phosphate reacts with aspartate, carbamoylaspartate is formed (which is catalyzed by transcarbamoylase). The orotic acid formed thereafter is carbamoylaspartate.In addition to aspartate transcarbamoylase, the end products (UTP, CTP) inhibit this site as well.
The pyrimidine metabolizes to soluble compounds that can be readily removed or used.
The breakdown of cytosine produces *-alanine, CO2, and NH3 as products.Thymine produces NH3, CO2, and *-aminoisobutyrate.The amino acid isobutyrate is converted into succinyl-CoA.
By phosphorylating other nucleoside triphosphates (catalyzed by nucleoside kinase), nucleoside di- and triphosphate are biosynthesised from nucleoside monophosphate.
By reducing already bound ribose to nucleotides, deoxyribonucleotide biosynthesis can occur.There is a need for NADPH and thioredoxin.
It has been found that many nitrogenous bases release histamine, and the simplest of all, ammonia, is very potent (Garan, 1938; Schild, 1949).In some cases, alkaloids, such as atropine, strychnine, and curare (or D-tubocurinine), have been shown to release histamine from various structures (Burstein and Parrot, 1949; Alam et al., 1939; Schild and Gregory, 1947).The release of histamine from the dog's gastrocnemius was demonstrated by Alam et al. (1939) and confirmed by Child and Gregory (1947).The perfusion of the rat's hindlimbs through a cannula tied in the abdominal aorta resulted in the release of histamine when D-tubocurarine was injected into the cannula (Rocha e Silva and Schild, 1949).The repeated injections of curare caused very large amounts of histamine to be released in this type of experiment.Each time, a molar ratio of curarine/histamine varying from 20 to 51 was observed, and amounts ranging from 5 to 35.6*g were released by 2-6 mg of D-tubocurarine.Rocha e Silva and Schild (1949) studied D-tubocurarine's histamine-releasing capacity by observing the amounts of histamine released by rat diaphragms. In order to have more reliable data on the quantities of histamine released by this substance, they used a piece of rat's diaphragm.For control pairs, we used the two lateral segments of the diaphragm.Each half of the diaphragm, weighing 150 to 300 mg, was attached to platinum hooks fused to the capillary glass tubes, poured into warm oxygenated Tyrode solution, and then added to the experimental solution containing d-tubocurarine.In the end, the muscle was removed from the solution and placed in a fresh solution of d-tubocurarine.An isolated guinea pig gut was tested for the presence of histamine in the solution.The figure 31 shows 106 measurements of histamine release by curarine.
They tested the histamine-elimination capacity of substituted amines containing the guanidine group or related radicals.These bases included diamines, diamidines, diguanidines, diisothioureas, diquaternaries, and some benzamidine derivatives.After intravenous administration to cats and dogs, many of them caused a sudden drop in arterial pressure after a latency of 20–25 seconds.When injected into human skin, such compounds as diamino-octane, diamidinodecane, diguanidinopentane, and diisothiourea produce wheals.At least two of these compounds, propamidine and 1,8-diamino-octane, are thought to act by liberating histamine, because they have decreased levels of histamine in the blood of animals given these compounds in dosages ranging from 5 to 15 mg/kg.The drug licheniformin, extracted from Bacillus licheniformis, also gave similar results by Callow et al. (1947).Following diamino-octane dihydrochloride injection (15 mg/kg) into a dog's vein, there occurred an increase in blood histamine levels (up to 3 g/ml of plasma) and fluidity of the blood, which remained fluid for more than 24 hours.Toluidine blue was added to restore clotting time to normal levels, which indicates that heparin was the agent responsible for this increase.Injection of peptone has a similar effect to these simple bases, suggesting a common mechanism.Licheniformin, a simple polypeptide, has been shown to produce similar effects, which confirms this belief.A more remote possibility is that anaphylaxis may work by releasing simple bases such as diamines and diamidines.
According to Paton (1951; Mongar and Schild, 1952; Feldberg and Talesnik, 1953), compound 48/80 obtained from p-methoxyphenethylmethylamine was the most potent basic releaser.There is also an interesting fact that this compound also releases heparin from dog's liver (MacIntosh, personal communication), but not from rats' organs (Mota et al., 1953), but it causes rapid destruction of mast cells in the rat's skin.The possibility that a similar compound may be responsible for anaphylactic shock was suggested by Mongar and Schild (1952), who observed a correlation between the proportion of histamine released by guinea pig tissues when they were exposed to compound 48/80 or egg albumin.Even though the parallel is striking, certain peculiarities of the mode of action of each agent preclude any speculation that the final mediator for the histamine release in anaphylaxis could be a simple compound.As an example, 48/80 was applied to intestine before contact with egg albumin, and this resulted in an increased release of histamine, but when the order of addition was reversed, egg albumin had no effect on the further release produced by 48/80. .It appears likely that these compounds work through an intermediary agent found in certain organs (the skin of rats for example) but not others.
For a thorough description of the basic agents that release histamine, see Paton and Rothschild (1957, 1966).
It was believed that the release of histamine by 48/80, diamines, diamidines and so forth could be explained by the simple displacement of histamine by basic compounds, in a way similar to that caused in a cationic exchange resin by stronger bases.Several studies have found that histamine can be retained in solution by heparin, and since mast cells are very rich in acid sulfated polysaccharides, these may be able to act as a natural means of retaining histamine within the granules of mast cells.Lagunoff et al. (1964) and Uvnäs (1964) presented direct evidence that histamine bound to heparin, as we have seen above.This experiment only proved that a small portion of histamine (about one-fifth) may be retained in mast-cell granules by salt-linkage.
Histamine and heparin are both released from liver mast cells in free form during anaphylactic shock in dogs, which makes it difficult to explain how histamine can combine with heparin in places previously occupied by histamine in this case.A strong similarity exists between the mechanism of histamine release by basic compounds (48/81) from rat mast cells and the mechanism of histamine release from guinea-pig lung and rabbit platelets, structures where basic compounds have only a small effect or none at all.The next section will describe the mechanism of release rather than the activation or inhibition of enzymes responsible for carbohydrate metabolism.