Nucleotides are joined together through the phosphate group of one nucleotide connecting in an ester linkage to the OH group on the third carbon atom of the sugar unit of a second nucleotide. This unit joins to a third nucleotide, and the process is repeated to produce a long nucleic acid chain Figure The purine and pyrimidine bases branch off this backbone.
Each phosphate group has one acidic hydrogen atom that is ionized at physiological pH. This is why these compounds are known as nucleic acids. Like proteins, nucleic acids have a primary structure that is defined as the sequence of their nucleotides.
Unlike proteins, which have 20 different kinds of amino acids, there are only 4 different kinds of nucleotides in nucleic acids. For amino acid sequences in proteins, the convention is to write the amino acids in order starting with the N-terminal amino acid.
In writing nucleotide sequences for nucleic acids, the convention is to write the nucleotides usually using the one-letter abbreviations for the bases, shown in Figure For DNA, a lowercase d is often written in front of the sequence to indicate that the monomers are deoxyribonucleotides. The sequence of nucleotides in the DNA segment shown in Figure Identify the three molecules needed to form the nucleotides in each nucleic acid.
For each structure, circle the sugar unit and identify the nucleotide as a ribonucleotide or a deoxyribonucleotide. For each structure, circle the nitrogenous base and identify it as a purine or pyrimidine. Steven Farmer Sonoma State University.
Objectives After completing this section, you should be able to outline the relationship between nucleic acids, nucleotides and nucleosides. Key Terms Make certain that you can define, and use in context, the key terms below. Study Notes The five bases that are found in nucleotides are often represented by their initial letter: adenine, A; guanine, G; cytosine, C; thymine, T; and uracil, U.
To fulfill Objective 6, you should be able to reproduce the figure below. Primary Structure of Nucleic Acids Nucleotides are joined together through the phosphate group of one nucleotide connecting in an ester linkage to the OH group on the third carbon atom of the sugar unit of a second nucleotide. Note Each phosphate group has one acidic hydrogen atom that is ionized at physiological pH. Concept Review Exercises Identify the three molecules needed to form the nucleotides in each nucleic acid.
A lack of folic acid leads to the reduced synthesis of purine nucleotides. This deficiency is particularly apparent in processes with high cell turnover, e. A consequence of folic acid deficiency, in this context, is megaloblastic anemia. In this condition, a malfunction occurs both in DNA synthesis as well as in the nuclear maturation during myelopoiesis, which leads to the appearance of megaloblasts. Besides folic acid deficiency, megaloblastic anemia can also occur due to a lack of vitamin B, which, overall, is a more common cause of megaloblastic anemia than the former.
Other symptoms of folic acid deficiency include gastritis and dermatitis. Folic acid deficiency during pregnancy increases the risk of the baby being born with spina bifida. Folic acid is composed of p-aminobenzoic acid , glutamine, and pteridine molecules.
Folic acid is available in its biologically active form as tetrahydrofolic acid TH-4 , which plays a role in the synthesis of purine nucleotides. The active form of folic acid functions as a coenzyme in C-1 transmission, in which the groups on the C-1 position are bound to the N atoms at positions 5 and 10 of the pteridine or 4-aminobenzoic acid moiety. The possible groups that can be transferred in this context are methyl, hydroxyl, and formyl groups.
Tetrahydrofolate synthesis occurs in the presence of dihydrofolate reductase. This enzyme can be inhibited by several drugs including trimethoprim. The intermediate product of pyrimidine synthesis is initially a ribonucleotide. The biosynthesis of pyrimidine nucleotides occurs over multiple steps involving different enzymes.
The pyrimidine ring is synthesized first and the ribose sugar is subsequently added to it. In the first step of pyrimidine synthesis, the carbamoyl phosphate and aspartate react to produce carbamoyl aspartate along with the release of a phosphate moiety. This reaction is catalyzed by aspartate transcarbamoylase.
Note : The key reaction in pyrimidine synthesis represents the reaction between carbamoyl phosphate and aspartate to form carbamoyl aspartate. Carbamoyl aspartate loses a water molecule to form d ihydroorotic acid. This second step involves the cyclization of carbamoyl aspartate in the presence of the enzyme, dihydroorotase. Next, dihydroorotic acid is oxidized to orotic acid in the presence of orotic acid dehydrogenase.
Orotic acid reacts with phosphoribosyl pyrophosphate PRPP to form orotidinephosphate with the release of pyrophosphate. This reaction is mediated by orotate phosphoribosyltransferase. O rotidinephosphate undergoes decarboxylation to form uridinephosphate UMP in the presence of orotidinephosphate decarboxylase. U ridinephosphate constitutes the building block of the subsequent reactions. On the other hand, uridinephosphate can be reduced to d-UMP by the action of d-TMP-synthetase thymidylate-synthase.
The methyl group that is required for this conversion is obtained from N 5 , N 10 -methylene tetrahydro folate , which in turn is converted to dihydrof olate. Ribonucleotide reductase catalyzes this reaction in the presence of thioredoxin as a cofactor. Thioredoxin, in turn, contains two SH groups , which are converted to the disulfide form after reduction. Similar to the stepwise synthesis of purine nucleotides, their degradation also occurs via multiple steps.
The steps involved in degradation depends on the purine bases adenosine or guanosine that are present. The first step in the degradation reaction is the conversion of the nucleotide to the nucleoside. This occurs through a hydrolysis reaction mediated by nucleotidase. Additionally, a phosphate molecule is lost, which leads to the formation of a free base purine or pyrimidine and ribosephosphate.
This step is mediated by nucleoside phosphorylase. The degradation of the purine bases, adenosine and guanosine, occurs subsequently. First, adenosine undergoes deamination in the presence of adenosine deaminase and is converted to inosine. The second step is identical for both inosine and guanosine, in which they are converted to hypoxanthine and guanine, respectively, through an ATP-dependent removal of ribose.
Similar to the previous step, this reaction is mediated by nucleoside phosphorylase. In the next step, inosine and hypoxanthine are converted to xanthine. However, this step proceeds differently for each nucleoside.
Guanine is deaminated to xanthine, whereas hypoxanthine is oxidized to xanthine in the presence of xanthine oxidase. Note : Xanthine oxidase is an iron-bearing flavoprotein that contains a molybdenum atom in its active center. Another reaction mediated by xanthine oxidase is the conversion of xanthine to uric acid. This step also proceeds via oxidation, where molecular oxygen serves as a means for oxidation. Eventually, the uric acid that is generated is excreted in the urine.
When this level is exceeded, urate crystals are formed, which accumulate in tissues and joints leading to local inflammation or gout. Poor vascularization and low temperatures promote the crystallization of uric acid, which likely explains why the metatarsophalangeal joint podagra , cornea, and the lens of the eye are potential sites for uric-acid deposition.
Gout-affected joints appear flushed, overheated, and swollen, and are very painful. These presentations represent the cardinal signs of inflammation rubor, calor, tumor, and dolor. Enzyme defects can also lead to increased or diminished uric acid levels. A partial or complete lack of hypoxanthine-guanine phosphoribosyltransferase results in increased uric acid levels.
A deficiency of this enzyme results in a condition known as Kelley-Seegmiller syndrome , which is associated with high purine levels. Lesch-Nyhan syndrome is a condition resulting from the complete lack of hypoxanthine-guanine phosphoribosyltransferase. The affected children present a trio of hyperuricemia, progressive kidney insufficiency, and neurological symptoms, for example, a tendency to self-mutilate.
Conversely, reduced xanthine oxidase activity can lead to diminished uric acid levels and the accumulation of xanthine xanthinuria. Note : Xanthine oxidase activity can be inhibited using allopurinol during the management of gout.
Some other factors influencing uric acid levels include renal function uric acid secretion , an increased cell turnover diseases including leukemia , or high-purine foods beer, fish, and certain meats. The first step in the degradation of pyrimidine nucleotides is their conversion to nucleosides, similar to that discussed in the degradation of purine nucleotides.
The degradation of cytosine and thymine, produced in the first step of the degradation of pyrimidine bases, occurs in the liver. Note : The pyrimidine ring is broken down during nucleotide degradation; however, the purine ring is preserved during the degradation process.
Cytosine and thymine undergo independent degradation pathways in which the reaction steps are identical except for the first step in the degradation of cytosine. In this first step, cytosine is degraded to uracil by the removal of an amino group. The nitrogen atoms resulting from the breakdown are utilized in the urea cycle.
The degradation of purine nucleotides does not result in any energy gain, whereas the breakdown of pyrimidine nucleotides results in only marginal energy generation. Since the synthesis of both purine and pyrimidine nucleotides requires significant energy, recycling is an energetically viable option.
This occurs via the salvage pathway. The exact steps involved in recycling are only known for purine bases and are discussed below.
First, the purine bases are phosphoribosylized to nucleotides by PRPP.
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