Nucleic acids,

The nucleic acid content of particulate matter in seawater has been employed as a parameter to describe the bioactive potential of this material. A knowledge of the DNA content of seawater may provide information on the growth of planktonic organisms and may further serve as a biomass indicator (Holm-Hansen et al., 1968), since there is some suggestion of a high logarithmic correlation of DNA to carbon content per cell (Holm-Hansen, 1969). This point is at present disputed (Skjoldal and Bamstedt, 1976). 

Derenbach (1970) made a distinction between soluble and combined RNA of planktonic material from the different behaviour of these compounds after different extraction procedures. He and others (see Derenbach, 1970 for references), employed the orcinol/hydrochloric acid reagent according to Ceriotti (1955). Since a variety of other sugars may interfere (see section 3.1 orcinol/sulphuric acid has also been used as a reagent for total carbohydrate determinations) correction factors or preferably chromatographic separations of the extracts are required for quantitative results. 

Iwamura et cil. (1970) obtained DNA and RNA fractions after several extraction and purification steps to remove lipids, pigments and proteins (also characterised from the common extract). 

DNA was then determined by the Kissane—Robins method RNA was estimated from the difference in optical densities at 260 and 320 nm. 

Since total methods yield only a limited amount of information, Breter et al. (1977) after precipitation of the polyanionic fraction and subsequent hydrolysis, separated the extracted DNA and RNA bases by HPLC. A complete run including adenine, cytosine, guanine, thymine and uracil lasted approximately 130 min, although this figure may easily be reduced by use 

Nucleic acids are biomolecules that pass genetic information from one generation to the next. Nucleic acids contained in DNA, deoxyribonucleic acid, and RNA, ribonucleic acid, are responsible for how all higher organism develop into unique species. DNA is present in the nucleus of all cells where segments of DNA comprise genes. DNA carries the information needed to produce RNA, which in turn produces protein molecules. A simplified view of the role of nucleic acids is to produce RNA, and the role of RNA is to produce proteins. 

Shows that 2-deoxyribose and ribose are identical except for an oxygen atom absent on the second carbon. Carbons are numbered for future reference. 

The sugar and phosphate groups form the backbone of a nucleic acid, and the amine bases exist as side chains. A nucleic acid can be thought of as alternating sugar-phosphate units with amine base projections  

Like proteins, DNA and RNA exhibit higher order structure that dictates how these molecules function. Determining the structure of DNA challenged the world s foremost scientists during the middle of the 

A nucleotide is formed when hydrogen phosphate derived from phosphoric acid combines with a sugar and nitrogen base. Several different nitrogen bases may form a nncleotide, and the hexagon is used as a general symbol for any one of these. 

Nucleic acids are the fourth class of biological molecules that you will study. They are the information-storage molecules of the cell. This group of nitrogen-containing molecules got its name from the cellular location in which the molecules are primarily found— the nucleus. It is from this control center of cells that nucleic acids carry out their major functions. 

You ve probably heard of DNA (deoxyribonucleic acid), one of the two kinds of nucleic acids found in living cells. DNA contains the master plans for building all the proteins in an organism s body. 

Q Each nucleotide contains a nitrogen-containing base, a five-carbon sugar, and a phosphate group. 

The function of DNA Watson and Crick used their model to predict how DNA s chemical structure enables it to carry out its function. DNA stores the genetic information of a cell in the cell s nucleus. Before the cell divides, the DNA is copied so that the new generation of cells gets the same 

The structure of DNA is a double helix that resembles a twisted zipper. 

2 Nucleic Acids. - Recent EPR studies of radical attack and formation upon DNA are reported elsewhere in this volume, by Sevilla and Becker, and therefore will not be described here in any detail. Findings of particular biomedical relevance include the spin trapping of radicals resulting from the decomposition of chloramines formed in the reaction of HOC1 with polynucleosides, RNA and 

DNA 196 other such studies have been concerned with the mechanisms of damage to DNA upon exposure to xenobiotics (examples of which occur throughout this Report). 

DNA deoxyribonucleic acid—the natural polymer that stores genetic information in the nucleus of a cell 

RNA ribonucleic acid—a natural polymer used to translate genetic information in the nucleus into a template for the construction of proteins 

All RNA molecules are single-stranded molectiles. RNA molecules are synthesized from DNA templates in a process known as transcription these molecules have a number of vital roles within cells. It is convenient to divide RNA molecules into the three functional classes, all of which function in the cytoplasm. 

Messenger RNA (mRNA) contains the information (formerly residing in DNA) that is decoded in a way that enables the manufacture of a protein, and migrates from the nucleus to ribosomes in the cytoplasm (where proteins are assembled). A triplet of nucleotides within an RNA molecule (called a codon) specifies the amino acid to be incorporated into a specific site in the protein being assembled. A cell s population of mRNA molecules is very diverse, as these molecules are responsible for the synthesis of the many different proteins found in the cell. However, mRNA makes up only 5 percent of total cellular RNA. 

Ribosomal RNA (rRNA) is the most abundant intracellular RNA, making up 80 percent of total RNA. The eukaryotic ribonucleoprotein particle (ribosome) is composed of many proteins and four rRNA molecules (which are classified according to size). Ribosomes reside in the cytoplasm and are the molecular platform (the actual physical site o for protein synthesis. 

The nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are the chemical carriers of a cell s genetic information. Nucleic acids are biopolymers made of nucleotides joined together to form a long chain. These biopolymers are often found associated with proteins, and in this form they are called nucleoproteins. Each nucleotide comprises a nucleoside bonded to a phosphate group, and each nucleoside is composed of an aldopentose sugar, ribose or 2-deoxyribose, linked to a heterocyclic purine or pyrimidine base (see Section 4.7). 

The sugar component in RNA is ribose, whereas in DNA it is 2-dexoyribose. In deoxyribonucleotides, the heterocyclic bases are purine bases, adenine and guanine, and pyrimidine bases, cytosine and thymine. In ribonucleotides, adenine, guanine and cytosine are present, but not thymine, which is replaced by uracil, another pyrimidine base. 

Despite being structurally similar, DNA and RNA differ in size and in their functions within a cell. The molecular weights of DNA, found in the nucleus of cells, can be up to 150 billion and lengths up to 12 cm, whereas the molecular weight of RNA, found outside the cell nucleus, can only be up to 35 000. 

2 -Deoxyadenosine 5 -phosphate Adenine + deoxyribose + phosphate Nucleoside is 2 -deoxyadenosine, composed of adenine and deoxyribose 

The nucleic acids DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) carry the cell s genetic information. Indeed, DNA contains all the information needed for the survival of the cell. 

The structures of both DNA and RNA depend on the sequence of the nucleotides (i.e. the amine bases). Watson and Crick showed that DNA is a double helix composed of two strands with complementary bases, which hydrogen bond to one another. A and T form strong bonds to one another, as does C and G. 

RNA is formed by the transcription of DNA. On cell division, the two chains of the helix unwind, and each strand is used as a template for the construction of an RNA molecule. The complementary bases pair up, and the completed RNA (which corresponds to only a section of the DNA) then unwinds from DNA and travels to the nucleus. Unlike DNA, RNA remains a single strand of nucleotides. 

The sequence of amino acids in a protein is called the primary structure while the localised spatial arrangement of amino acid segments is called the secondary structure. The secondary structure results from the rigidity of the amide bond and any other non-covalent interactions (e.g. hydrogen bonding) of the side-chains. Secondary structures include the a-helix and the -pleated sheet. The tertiary structure refers to the way in which the entire protein is folded into a 3-dimensional shape, and the quaternary structure refers to the way in which proteins come together to form aggregates. 

Large proteins, which act as catalysts for biological reactions, are called enzymes. The tertiary structure of enzymes usually produces 3-dimensional pockets called active sites. The size and shape of the active site is specific for only a certain type of substrate, which is selectively converted into the product by the enzyme. This is often compared to a key fitting a lock (the lock and key model). The catalytic activity of the enzyme is destroyed by denaturation, which is the breakdown of the tertiary structure (i.e. the protein unfolds). This can be caused by a change in temperature or pH. 

Both DNA and RNA are composed of phosphoric acid (H3PO4), a sugar, and several heterocyclic organic bases. DNA contains the sugar deoxyribose and RNA contains ribose. The bases adenine (A), guanine (G), cytosine (C) and thymine (T) are present in DNA, while adenine (A), guanine (G), cytosine (C) and uracil (U) are present in RNA. 

A heterocycle is a cyclic compound in which at least one atom is not carbon 

To form a polymer, nucleotides covalently link in long chains called polynucleotides. The linkage is always between the monosaccharide of one nucleotide and the phosphate group of the next. 

This linkage results in a repetitive monosaccharide-phosphate backbone in all polynucleotides. 

FIGURE 2.6 Basic units of nucleic acid polymers. These units act as a code in directing reproduction and other activities of organisms. Dashed lines show bonds to next nucleotide unit. 

In directing protein synthesis, DNA becomes partially unraveled and generates a complementary strand of material in the form of RNA, which in turn directs protein synthesis in the cell. 

Consideration of nucleic acids and their function is very important in the development of green chemistry and the practice of sustainable chemical science. One aspect of this relationship is that the toxicity hazards of many chemical substances result from potential effects of these substances on DNA. Of most concern is the ability of some substances to alter DNA and cause the uncontrolled cell replication that is cancer. Also of concern is the ability of some chemical substances called mutagens to alter DNA such that undesirable characteristics are passed on to offspring. 

Another important consideration with DNA as it relates to green chemistry is the ability that humans now have to transfer DNA between organisms, popularly called genetic engineering. An important example is the development of bacteria that have the DNA transferred from humans to make human insulin. This technology of recombinant DNA is discussed in more detail in Chapter 13. 

The directed synthesis of deoxyribonucleic acid (DNA) and its manipulation for genetic engineering would be impossible without enzyme catalysis. There is a range of restriction enzymes which can break DNA strands at specific points defined by the local base sequence, as well as ligases which can rejoin the broken ends where new base sequences are inserted, and they are essential catalysts. They complement the chemical synthesis of the oligonucleotides (small segments of DNA) which are inserted. A discussion of the technique is outside the scope of this chapter, largely because the 

The importance of nucleic acids both in regard to cell replication and growth has been recognized for many years (Fig. 3).  

therefore, surprising to find that apart from the work of a relatively limited number of workers, little information is available on the effects of humic substances on these important cell constituents. 

FIGURE 3. Simplified scheme for the role of nucleic acids in protein synthesis. 

In eiakaryotes gene expression occurs by multiple mechanisms some of which in higher plants involve 

Gorovaya and Solocha noticed that HA increased the volume of interphase nuclei in meristematic tissues of maize, onion and wheat. In a 

The basic monomers of nucleic acids are nucleotides which are made up of heterocyclic nitrogen-containing compounds, purines and pyrimidines, linked to pentose sugars. There are two types of nucleic acids and these can be distinguished on the basis of the sugar moiety of the molecule, Ribonucleic acids (RNA) contain ribose, while deoxyribonucleic acid (DNA) contains deoxyribose. The bases cytosine (C) adenine (A) and guanine (G) are common in both RNA and DNA. However, RNA molecules contain a unique base, uracil (U), while the unique DNA base is thymidine (T). These differences in the base structure markedly affect the secondary structures of these polymers. The structures of DNA and RNA are outlined in Appendix 5.2. 

There are two types of nucleic acids ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). One of the ways in which they differ is in the carbohydrate that they contain. The two carbohydrates in nucleic acids are ribose (contained in RNA) and 2-deoxyribose (contained in DNA) these carbohydrates differ in the presence or absence of an oxygen atom on carbon 2. 

Unless olheiwise noted, all content on this page is O Cengage Learning. 

Cellular metal ion transport is biologically important because our muscular and nervous systems are regulated by charged species. Cells use membrane channels to extract potassium ions selectively from environments containing both K+ and Na+. Because the K+ ion is /argerthan the Na+ ion, this process cannot be accomplished by simply restricting the channel diameter. Dr. Roderick MacKinnon showed that potassium selectivity arises from a preferential interaction between the potassium cation and the atoms of the protein amino acids composing the channel walls. 

K+ and Na+ ions initially enter the ion channel as solvated species, encased in shells of H2O molecules. However, they must eventually shed their water to pass through narrow rings of 

Tube-and-ribbon representation of tbe X-iay stnictnre of a potassinm ion channel by Roderick MacKinnon (Rockefeller University), who received the 2003 Nobel Prize in Chemistry for this work. The key K ion-selectii% portion of the channel is shown wtth side and top-down expansions nsing space-fillii models of the C = 0 groups that line the channel and blue potassium ions. 

There are currently two pellicular anion exchangers for nucleic acid analysis available DNAPac PAIOO and PA200, the latter one being the successor product of the PAIOO column [332]. Both columns have been developed for a wide range of DNA samples, including ssDNA and RNA.The structural and technical properties of these two columns are summarized in Table 3.39. 

Tautomeric forms of thymine- or uracil-containing oligonucleotides 

Larger scale purifications can also be accomplished by severely overloading the analytical capacity of the column and still collect fractions of high purity. This approximates the process of displacement chromatography. Under these conditions. 

Sodium chloride or sodium perchlorate gradients can also be applied to the separation of longer single-stranded oligonucleotides up to 60 bases in length 

NaCI (pH 8.4) eluent for (b) linear gradient from 25 mmol/L NaOH -i- 25 mmol/L Tris-CI -I- 0.5 mol/L NaCI (pH 12.4) to 25 mmol/L NaOH -I- 25 mmol/L Tris-CI -I- 0.9 mol/L NaCI (pH 12.4) flow rate  

The biological importance of nucleic acids began to emerge with the discovery by Oswald Avery, and his colleagues at the Rockefeller Institute, that the 

The structure of the DNA molecule is intimately related to its two primary roles replication (gene duplication by synthesis of more DNA) and transcription (gene expression by synthesis ofRNA) (see Fig. 4.1). 

In the nucleus, DNA is synthesized from mononucleotides (such as deoxy-adenosine triphosphate) by a polymerase. Some preformed DNA is required as a template. Several substances are known which inhibit this synthesis by combining with the template and making it unavailable (for example, the acridines). Many tumour-producing viruses, which have RNA as their sole nucleic acid, contain reverse transcriptase, i.e. a polymerase that forms new DNA as a copy of viral RNA (Temin and Mizutani, 1970). Agents to inhibit this enzyme selectively are being sought. 

The four bases mentioned account for most of those found in the DNA of higher forms of life. 5-Methylcytosine forms the principal exception 25% of the cytosine in the DNA of plants is in this form, but animal DNA has much less, and bacterial DNA has only 0-2% (Vanyushin etaLy 1968). Bacterial and viral DNAs sometimes contain other methylated bases, such as 6 -methyladenine, 2-methyladenine, or 5-hydroxymethyluracil. In some phages, all cytosine is replaced by 5-hydroxymethylcytosine, made by a virus-induced enzyme in the bacterial host (Cohen, 1963). 

The ratio of bases in bacterial DNA differs greatly, from one bacterial species to another, in that the sum of the two amphoteric bases (G+C), when divided by the sum of the two monofunctional bases (T+A), ranges between 0.45 and 2.80. In higher plants and animals, on the contrary, this ratio is confined between 0.6 and 0.9 (Belozersky and Spirin, 1958). 

Deoxyribonucleic acid DNA the most important of the nucleic acids, occurs in mitochondria and chloroplasts, but most of it is in the nucleus. It is the carrier of all the cell s genetic information, the appropriate portion of which is placed in service instantly to meet changing circumstances in the cell. The information stored in DNA is encoded by the nature and order of the pyrimidine bases, thymine 4.1b) and cytosine (4.2), and the purine bases adenine 4.3) and guanine (4.4). Each strand of DNA has a deoxyribose-phosphoric acid backbone to which these bases are attached. Usually DNA has two such strands woimd around one another in a double helix and held together by H-bonds between each opposing pair of bases (Watson and Crick, 1953 for bond lengths and angles, see Donohue, 1968). 

The absorption spectra produced by nucleic acids are due to their individual bases. The spectra can be obtained either for the whole molecule or for the individual 

In contrast to denaturation, renaturation is the process by which the separated DNA strands are brought back together. If the denatured sample is reheated from 0°C to Tin —25°C and maintained at —25°C, then renaturation can be determined 

DNA is a polymer composed of monomeric nucleic acids called nucleotides. A nucleotide consists of a nitrogenous base, sugar, and phosphoric acid (whereas a nucleoside consists of only the base and sugar see Fig. A2.4). 

There are two types of bases pyrimidines and purines (Fig. A2.5). The pyrimidine bases include cytosine, thymine, and uracil. Cytosine is found in 

Cells can be divided into germ cells and somatic cells. Germ cells are reproductive cells, for example, ova or sperm. Germ cells contain genetic characteristics that are passed on to the next generation. Somatic cells do not contribute their genes to future generations they are the tissue cells such as nerve cells and muscle cells. 

Within the cell is the nucleus with the chromosomes. DNA strands are housed within the chromosomes, together with some proteins. The 46 human chromosomes are grouped into 22 pairs and two sex chromosomes. Numbering of chromosomes is based on size, chromosome 1 being the largest and 22 the smallest. 

In addition to the 22 pairs, a female cell contains two X chromosomes and a male cell contains an X and a Y chromosome. When a female egg (carrying an X chromosome) combines with male sperm having an X chromosome, a female offspring is born. When the egg combines with a sperm having a Y chromosome, a male offspring results. 

DNA is a polymer composed of monomeric nucleic acids called nucleotides. 

A nucleotide consists of a nitrogenous base, sugar and phosphoric acid 

Appendix 2 Cells, Nucleic Acids, Genes and Proteins 

The unique combination of organic chemistry and molecular biology which is nowadays applied in nucleic acid synthesis and analysis led to a great interest in nucleic acid bioorganic chemistry. We give a few examples of recent synthetic endeavours in this field. 

1 DNA with a Site-Speciflcally, Covalently Bound Mutagen 

The unmodified and complementary oligonucleotides were also synthesized, in order to detect thermodynamic and spectroscopic differences between the double helices. Circular dichroism spectra revealed that the covalently bound anthracene does not stack in the centre of the DNA double helix. Mutagenic activity by intercalative binding of the anthracene residue is thus unlikely. Only in vitro and in vivo replication experiments with site-specifically modified 

The essence of life is contained in deoxyribonudeic add (DNA, which stays in the cell nucleus) and ribonucleic add (RNA, which functions in the cytoplasm). These substances, which are known collectively as nudeic adds, store and pass on essential genetic information that controls reproduction and protein synthesis. 

The formation of nucleic acid polymers from their monomeric constituents may be viewed as the following steps  

Nucleoside + phosphate yields a phosphate ester, a nudeotide  

I Nucleotide formed by the Q bonding of a phosphate tj group to deoxycytidine 

In die nucleic acid, the phosphate negative charges are neutralized by metal cations (such as Mg2+) or positively charged proteins (histoiies). 

In the past most of the studies on structure determination of nucleic acids were performed by proton NMR [513, 767, 768]. However, recent 13C NMR investigations have demonstrated that additional information can be obtained from the 13C spectra [769]. 

Because of their relatively low molecular weight (70 to 90 nucleotide residues), transfer ribonucleic acids are of special interest for 13C NMR investigations [769, 778, 782-784] of nucleic acids. Using a tube of 20 mm o.d., a sample of thermally denatured yeast 

C Atom Uridine Uridine-5 - phosphate Uridine-3 - phosphate Uridinc-2 - phosphate Polyuridylic acid 

The sequence of amino acids in a protein is determined by the genetic information coded into long-chain polymers called nucleic acids. The monomers that make up nucleic acids are called nucleotides. Each nucleotide is made up of three parts a phosphate group, a five-carbon sugar, and a nitrogen-containing cyclic compound called a nitrogen base. The structure of a nucleotide is shown below. 

Phosphate group 1 H H /V OH OH Sugar Nitrogen- containing base 

Solving Problems A Chemistry Handbook Chemistry Matter and Change 249 

The order of these four nitrogen bases along one of the DNA chains provides the information for the sequences of amino acids in proteins. Cell mechanisms read the DNA sequence in groups of three bases called triplets. Each triplet codes for a specific amino acid or tells the cell to start or stop making a protein.  

As the term nucleic acid suggests, a nucleic acid is a compound found in the nuclei of the cells of living organisms. There are two kinds of nucleic acids—deoxyribonucleic acid (DNA) and ribonucleic acid(RNA) Like carbohydrates and proteins, DNA and RNA are long-chain polymers. 

The genetic information that makes each organism s offspring look and behave like its parents is encoded in molecules called nucleic acids. Together with a set of specialized enzymes that catalyze their synthesis and decomposition, the nucleic acids constitute a remarkable system that accurately copies millions of pieces of data with very few mistakes. 

Like polysaccharides and polypeptides, nucleic acids are condensation polymers. Each monomer in these polymers includes one of two simple sugars, one phosphoric acid group, and one of a group of heterocyclic nitrogen compounds that behave chemically as bases. A particular nucleic acid is a deoxyribonucleic acid (DNA) if it contains the sugar 2-deoxy-D-ribose, and it is a ribonucleic acid (RNA) if it contains the sugar D-ribose. 

The five organic bases that play a key role in the mechanism for information storage are adenine (A), guanine (G), thymine (T), cytosine (G), and uracil (U). These bases are mentioned so often in any discussion of nucleic acid chemistry that to save space they are usually referred to only by the first letter of each name. 

Notice the presence of the OH group on the 2 carbon in D-ribose. The 2-deoxy-D-ribose does not have this OH group. 

Nucleic acids are found in all living cells, with the exception of the red blood cells of mammals. DNA occurs primarily in the nucleus of the cell, and RNA is found mainly in the cytoplasm, outside the nucleus. There are three major types of RNA, each with its own characteristic size, base composition, and function in protein synthesis (as described later in this section) messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). 

Although the majority of drugs act on protein structures, there are several examples of important drugs which act directly on nucleic acids to disrupt replication, transcription, and translation. 

The only stereogenic centers of DNA and RNA are found at the sugar carbons, and because the ribose or deoxyribose are enantiomerically pure, natural nucleic acids are isotactic. The P of the phosphodiester backbone of a nucleic acid is not a stereogenic center, but the two 0 groups of a connecting phosphate are diastereotopic. The phosphorus is thus prochi-ral. This has led to the use of labeled phosphates in mechanistic studies, as described with one example in a Connections highlight on the next page. 

RNA and DNA are in general very difficult to model with force-field based approaches. One major difficulty is to reproduce the backbone conformation (crucial for any modeling of nucleic acids), as the corresponding torsional energy barriers are very small [29]. First results from AIMD are encouraging the calculated structure of a hydrated GpG RNA duplex in laboratory realizable conditions (that is, in the crystal phase)[25] showed excellent agreement with experiment and provided the H-bond network postulated by the crystallographers. 

Investigations of platinum-based drugs [30, 31] and their adducts with DNA fragments in the solid state [32] and in aqueous solution [26] confirm the reliability of an AIMD scheme to describe these systems even in the presence of transition metal ions, which (as mentioned in Section 1) are notoriously difficult to treat with effective potentials [33]. 

These limitations of the classical Ilkovic equation have major implications for analogous measurements, not only with proteins as discussed already (buried depolarizer groups) but also for nucleic acids (extreme coil dimensions). 

The spectra of a free base and the corresponding nucleoside are quite similar, since only the purine or pyrimidine base component is a chromophore, giving rise to absorption in the region between about 250 and 270 nm at neutral pH. Because of protonation of the base nitrogen atoms, spectra of these compounds are also highly pH-dependent Nucleic acids have an absorption maximum close to 260 nm. The variation in absorption coefficient of DNA and RNA per nucleotide residue is small hence the absorption at 260 nm can be used as a measure of total nucleic acid concentration (7). However, the absorption of a native nucleic acid molecule cannot be expressed as a sum of absorbances of all the 

During the denaturation process, the double helix of the native DNA unwinds, the two strands separate as random coils, and weak interactions between neighbouring nucleotides are diminished. As a resxilt, denaturation is accompanied by an absorbance increase at 260 nm, the so alled hyperchromic effect. Measurement of the extent of the hyperchromic effect allows the progress of denaturation to be followed, for example, as a function of temperature, and the melting point of a DNA sample to be determined (see Chapter 13 for more details). 

In 1868 Friederich Miescher isolated a substance from the nucleus of pus cells, to be characteristic of the nucleus, and he called it nuclein. A similar substance isolated from salmon sperm heads. Nuclein was later shown to be a mixture of a 

Electron microscopy has shown that the double helical chain of DNA is folded, twisted and coiled into quite compact shapes. A number of DNA 

Replication, which starts at the end of a DNA helix, continues until the entire structure has been duplicated. The same result is obtained when replication starts at the centre of a DNA helix. In this case unwinding continues in both directions until the complete molecule is duplicated. This latter situation is more common. 

Primary and Secondary Structure. The DNA double helix was first identified by Watson and Crick in 1953 (4). Not only was the Watson-Crick model consistent with the known physical and chemical properties of DNA, but it also suggested how genetic information could be organized and rephcated, thus providing a foundation for modem molecular biology. 

The primary stmcture of DNA is based on repeating nucleotide units, where each nucleotide is made up of the sugar, ie, 2 -deoxyribose, a phosphate, and a heterocycHc base, N. The most common DNA bases are the purines, adenine (A) and guanine (G), and the pyrimidines, thymine (T) and cytosine (C) (Fig. 1). The base, N, is bound at the I -position of the ribose unit through a heterocycHc nitrogen. 

Kirk-Othmer Encyclopedia of Chemical Technology (4th Edition) 

The nucleotides are linked together via the phosphate groups, which connect the 5 -hydroxyl group of one nucleotide and the 3 -hydroxyl group of the next to form a polynucleotide chain (Fig. la). DNA is not a rigid or static molecule rather, it can adopt a variety of hehcal motifs. 

Note Total RNA (3 jug) was added in each case and translation mixtures (18 jul) were incubated for 90 min at 30°C. 

Our knowledge of nucleic acids and nucleic acid metabolism in cestodes is very limited when compared with many other organisms. Nevertheless, some recent advances have been made and it is clear that new approaches in 

As much of the terminology used in molecular biology may be unfamiliar to some readers, it is appropriate to define some of the vocabulary and this is given in an appendix to this chapter. There are two types of nucleic acids, the ribonucleic acids (RNA) and the deoxyribonucleic acids (DNA). Genetic information is carried in the linear sequence of nucleotides in DNA. Each molecule of DNA contains two complementary strands of deoxyribonucleotides which contain the purine bases, adenine and guanine and the pyrimidines, cytosine and thymine. RNA is single-stranded, being composed of a linear sequence of ribonucleotides the bases are the same as in DNA with the exception that thymine is replaced by the closely related base uracil. DNA replication occurs by the polymerisation of a new complementary strand on to each of the old strands. 

Expression of the genetic information occurs when a specific segment of DNA (called a coding region or gene) is copied in the nucleus into RNA by a process called DNA transcription. The RNA is modified before it leaves the nucleus as a mRNA molecule to direct the synthesis of a specific protein on a ribosome by translation. 

As with purines, there is indirect evidence from studies in vitro that regenerating tetrathyridia of M. corti can synthesise pyrimidines de novo (315). Furthermore, aspartate transcarbamylase, the first enzyme in the pathway, has been demonstrated in Moniezia benedini (39), while five of the six pathway enzymes have been measured in H. diminuta (326). It appears, therefore, that at least some cestodes have the capacity to synthesise pyrimidines by the biosynthetic route. Little is known of pyrimidine salvage pathways in cestodes, although the key enzyme thymidine kinase has been 

The determination of the structure of the DNA molecule is arguably the greatest achievement in structural chemistry of the twentieth century. A key feature of 

The structures and energies of the tautomers of the bases of the nucleic acids have been subject to numerous computational studies. Since DNA is found in the aqueous environment of the cell interior, it is essential that the base tautomers, and the base pairs, be computed in the aqueous phase. In this section, we discuss the structures of the tautomers of each of the four DNA bases and uracil, found in RNA, focusing on the differences in the gas and solution phases. We then take on the structure of the base pairs in solution. 

Globular Proteins. Despite their importance, globular proteins are not as thoroughly studied as fibrous ones. They include, for example, albumin and hemoglobin. There have been some suggestions which, with one exception, have involved H bonds. This exception, Wrinch s cyclol theory (see, for example, 2202-2204), is of only p2issing interest, but its lack of conformity witK tha observed H bonding (as indicated by IR spectra) was one factor in its rejection. See 1602 for a criticism of the cyclol theory. 

Pauling and Corey (1599) made the point that under certain conditions globular proteins can be converted to forms similar to j8-keratin, and on this basis they proposed the a-helix as a basic feature in fRe structure. Perutz s x-ray work (256, 1614) shows that parts of horse hemoglobin may have this structure. Ambrose and Elliott (35) present some IR work on globular proteins in a paper which particularly stresses the functions of H bonds. 

Nucleic acids constitute another vit il class of compounds. They have received particular attention because of their presence in viruses and because of the part they play in reproduction, gene carrying, and the growth process. 

In Fig. 10-8 the spiraling ribbons represent sugar-phosphate chains and the bars represent pairs of bases H bonding the chains together. Each base is a purine or pyrimidine analogue and contains H bonding acid and base groups such that the pair is held by two or more H bonds (see Fig. 

The additional bond is thought to increase the specificity of pairing suggested by Watson and Crick. 

Reminder about Fischer projections, first introduced in Chapter 5, section 5-10 vertical bonds are equivalent to dashed bonds, going behind the plane of the paper, and horizontal bonds are equivalent to wedge bonds, coming toward the viewer. 

All four of these compounds are chiral and optically active. 

Production of one equivalent of formic acid, and two fragments containing two and three carbons respectively, proves that the glycoside was in a six-membered ring. 

23-44 Lactose is a hemiacetal. Therefore, it can mutarotate and is a reducing sugar. 

23-45 Gentiobiose is a hemiacetal in water, the hemiacetal is in equilibrium with the open-chain form and can react as an aldehyde. Gentiobiose can mutarotate and is a reducing sugar. 

Raman spectroscopy has been used extensively for the investigation of 

Review Vocabulary genetic information an inherited sequence of RNA or DNA that causes traits or characteristics to pass from one generation to the next 

OnnHES Nucleic acids store and transmit genetic information. 

Real-World Reading Link DNA testing is becoming more routine in medicine, forensic science, genealogy, and identification of victims in disasters. Modern techniques have made it possible to get a useful DNA sample from surprising sources, such as a strand of hair or dried saliva on a postage stamp. 

Nucleic acids are linear chains of alternating sugars and phosphates. Attached to every sugar is a nitrogen base. Because the nucieotides are offset, the chains resembie steps in a staircase. 

These are protein-bound polymers that are essential in many biological processes. They perform such functions as directing the syntheses of proteins in living cells and constitute the chemical basis of heredity. The polymers are polyphosphate esters of sugars that contain pendant heterocyclic amines, called bases  

There are two principle types of nucleic acid with two different sugars. One is D-2-deoxyribose found in deoxyribonucleic acid (DNA)  

The sugars are in the furanose form. They are linked through the hydroxy groups on carbons 3 and 5 as phosphate esters. The heterocyclic amine bases are attached at carbon 1, replacing the hydroxy group. 

A sugar molecule with a base attached to it is referred to as a nucleoside  

A nucleoside esterified with phosphoric acid is called a nucleotide  

Extensive research work has gone into modification of proteins, not for commercial applications but for academic reasons. Thus, for instance, Frances et al. developed a new reaction that introduces single reactive ketones or aldehydes at the N-terminal groups of protein when the proteins are mixed with pyridoxal phosphate [44]. The researchers also developed a palladium-catalyzed allylic alkylation that attaches long lipid tails to proteins, a process that can be used to customize the solubihty of enzymes, antibodies, viral capsids, and other proteins. 

037099 During mitosis spindle fibers are extranuclear. 037100 During mitosis spindle fibers are endonuclear. 037101 During mitosis nuclear envelope partially differen- 

037102 During mitosis nuclear envelope remains intact. 

038027 During sexual reproduction meiosis does not occur. 

038028 During sexual reproduction only portions of genetic complement are reassorted. 

038034 Mesosomes are associated with internal cell membranes. 

The substance acted on by an enzyme is called the substrate. Sucrose is the substrate of the enzyme sucrase. Common names for enzymes are formed by adding the suffix -ase to the root of the substrate name. Note, for example, the derivations of mal-tase, sucrase, and lactase from maltose, sucrose, and lactose. Many enzymes, especially digestive enzymes, have common names such as pepsin, rennin, trypsin, and so on. These names have no systematic significance. 

Enzymes act according to the following general sequence. Enzyme (E) and substrate (S) combine to form an enzyme-substrate intermediate (E-S). This intermediate decomposes to give the product (P) and regenerate the enzyme  

Enzyme-substrate interaction illustrating specificity of an enzyme by the lock-and-key model. 

A more recent model of the enzyme-substrate catalytic site, known as the induced-fit model, visualizes a flexible site of enzyme-substrate attachment, with the substrate inducing a change in the enzyme shape to fit the shape of the substrate. This model allows for the possibility that in some cases the enzyme might wrap itself around the substrate and so form the correct shape of lock and key. Thus, the enzyme does not need to have an exact preformed catalytic site to match the substrate. 

Explaining how hereditary material duplicates itself was a baffling problem for biologists. This explanation and the answer to the question Why are the offspring of a given species undeniably of that species eluded biologists for many years. Many thought the chemical basis for heredity lay in the structure of proteins. But they couldn t find how protein reproduced itself. The answer to the hereditary problem was finally found in the structure of the nucleic acids. 

P end-labelled Eco RI linkers were chromatographed, the recovery of the DNA fragments and the DNA linkers were found to be 98 % and 88 %, respectively. Eco RI cleaved pBR 325 DNA recovered by the method could be religated, and was capable of transforming coll with an efficiency equivalent to that of intact plasmid vectors. 

Phosphoproteins, which contain phosphoric acid as the prosthetic group, include the caseins of milk (see p. 406) and phosvitin in egg yolk. 

Chromoproteins contain a pigment as the prosthetic group. Examples are haemoglobin and cytochromes, in which the prosthetic group is the iron-containing compound haem, and flavoproteins, which contain flavins (see p. 90). 

Nucleic acids are high-molecular-weight compounds that play a fundamental role in living organisms as a store of genetic information they are the means by which this information is utilised in the synthesis of proteins. On hydrolysis, nucleic acids yield a mixture of basic nitrogenous compounds (purines and pyrimidines), a pentose (ri-bose or deoxyribose) and phosphoric acid. 

The main pyrimidines found in nucleic acids are cytosine, thymine and uracil. The relationships between these compounds and the parent material, pyrimidine, are shown below  

Adenine and guanine are the principal purine bases present in nucleic acids. 

Determination of the phospho lation pattern of ovalbumine. — Separator column ProPac SAX-10 eluant (A) 0.02 mol/L Tris/HCl — acetonitrile, pH 8.5, (B) 2 mol/L NaCi gradient linear, 0% B to 25% B in 15 min flow rate 1 mL/min detection UV (214 nm) sample 50 pg ovalbumine. 

25 mmol/LTris-HCl + 7.5 mmol/L NaCl04, pH 8, (B) 25 mmol/L Tris-HCl + 124 mmol/L NaCl04 gradient non-linear flow rate 1.5 mL/min detection UV (260 nm). 

15 Draw Lewis diagrams of adenine, cytosine, guanine, thymine, and uracil. 

17 Describe the process by which a protein molecule is formed. 

Two deoxyribose-phosphate backbones are joined to bases lying in the center. 

Complementary bases (blue) are connected by hydrogen bonds (dashed line). 

Hydrogen bonds are weaker than covalent bonds, and thus DNA can be unwound without damage. 

FIGURE 18.15 In the Induced-fit model, a flexible active site and substrate both adjust to provide the best fit for the reaction. Sucrose binds to the active site to align the glycosidic bond for hydrolysis. The monosaccharide products are released, and the enzyme binds to another sucrose. 

Q Why does the enzyme-catalyzed hydrolysis of sucrose go faster than the hydrolysis of sucrose In the chemistry laboratory  

LEARNING GOAL Describe the role of an enzyme in an enzyme-catalyzed reaction. 

49 Match the terms, (1) enzyme, (2) enzyme-substrate complex, and (3) substrate, with each of the following  

The planar enolate can reprotonate from either side, producing a mixture of erythrose and threose. 

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A constituent of the nucleic acid portion of nucleoproteins, and, combined, as adenosine pyrophosphate, it plays an important part in many metabolic processes. 

Protamines. Strongly basic, low mol. wt. proteins which contain high levels of arginine, but no sulphur-containing amino-acids. They are soluble proteins, associated with nucleic acids and are obtained in large quantity from fish spermatozoa. 

Nucleoproieins. The prosthetic group of the nucleoproteins is nucleic acid, often linked through salt linkages with protamines or histones. The nucleoproteins are present in the nuclei of all cells. Chromasomes are largely nucleoproteins and some plant viruses and bacteriophages have been shown to be pure nucleoproteins. See also histones. 

It is the parent substance of a group of compounds which includes cytosine, thymine and uracil, which are constituents of nucleic acids and barbituric acid and its derivatives, which are important medicinally. 

C4H4N2O2. Colourless crystalline powder, turning brown at 280 C and melting at 338 C (decomp.). Uracil is a constituent of ribose nucleic acid. Used as a diuretic and derivatives have pharmaceutical importance. 5-Fluorouracil is used in cancer treatment. 

Bustamente C, Keller D and Yang G 1993 Scanning force microscopy of nucleic acids and nucleoprotein assemblies Curr. Opin. Struct. Biol. 3 363... 

Hansma H G, Sinsheimer R L, Li M-Q and Hansma P K 1992 Atomic force microscopy of single- and double-stranded DMA Nucleic Acids Res. 20 3585... 

Williams J G K 1997 Single-molecule detection of specific nucleic acid sequences in unamplified genomic DNA Anal. Chem. 69 3915-20... 

Watson J D and Crick F H C 1953 A structure for deoxyribose nucleic acid Nature 171 737-8... 

J. McCammon and S. Harvey, Dynamics of proteins and nucleic acids, Cambridge University Press, Cambridge, U.K., 1987. 

McCammon and Harvey, 1987] McCammon, J. A., and Harvey, S. C. Dynamics of Proteins and Nucleic Acids. Cambridge University Press, Cambridge, 1987. 

Mathematical Model of the Nucleic Acids Conformational Transitions with Hysteresis over Hydration-Dehydration Cycle... 

Abstract. A model of the conformational transitions of the nucleic acid molecule during the water adsorption-desorption cycle is proposed. The nucleic acid-water system is considered as an open system. The model describes the transitions between three main conformations of wet nucleic acid samples A-, B- and unordered forms. The analysis of kinetic equations shows the non-trivial bifurcation behaviour of the system which leads to the multistability. This fact allows one to explain the hysteresis phenomena observed experimentally in the nucleic acid-water system. The problem of self-organization in the nucleic acid-water system is of great importance for revealing physical mechanisms of the functioning of nucleic acids and for many specific practical fields. 

Taking into account the hydration shell of the NA and the possibility of the water content changing we are forced to consider the water -I- nucleic acid as an open system. In the present study a phenomenological model taking into account the interdependence of hydration and the NA conformation transition processes is offered. In accordance with the algorithm described above we consider two types of the basic processes in the system and thus two time intervals the water adsorption and the conformational transitions of the NA, times of the conformational transitions being much more greater... 

The NAs such as DNA usually used in the experiments consist of 10" -1 o nucleotides. Thus, they should be considered as macrosystems. Moreover, in experiments with wet NA samples macroscopic quantities are measured, so averaging should also be performed over all nucleic acid molecules in the sample. These facts justify the usage of the macroscopic equations like (3) in our case and require the probabilities of finding macromolecular units in the certain conformational state as variables of the model. 

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