* Lecture 5 Heterocyclic Compounds. Structure, Properties and Biological Function of Nucleic Acids Lecturer: As. Professor, Department of Medical and Bioorganic Chemistry,, Ph.D. Kozub S.M. Kharkiv National Medical University Department of Medical and Bioorganic chemistry «Biological and Bioorganic Chemistry» * ACTUALITY OF THE LECTURE Heterocyclic structures are in the basis of numerous natural and biologically active substances and drugs. Heterocyclic molecules (indol, imidazole...) are included in some essential amino acids. A lot of drugs also contain heterocycles: non-narcotic analgesics contain pyrazolon-5, anti-tuberculosis drugs contain pyridine. * Heterocyclic structures are in the basis of numerous natural and biologically active substances and drugs. Alkylated pyrrole rings are the parent structures of important biologically active compounds, i.e. hem, chlorophyll, vitamin B12. Heterocyclic molecules (indol, imidazole, etc.) are included in some essential amino acids: e.g. tryptophan, histidine. A lot of drugs also contain heterocycles: non-narcotic analgesics contain pyrazolon-5, vitamin PP and anti-tuberculosis drugs contain pyridine. To know the structure and properties of nucleic acids is necessary to understand the essence of normal processes and pathology, the origin of hereditary diseases and problems of vital activity regulation. * Outline of the lecture Classification of heterocycles. Aromaticity of heterocycles. Biologically important compounds with five-membered heterocycles. Biologically important compounds with six-membered heterocycles. The structure and biochemical functions of nucleosides, nucleotides and nucleic acids. * HETEROCYCLIC COMPOUNDS are cyclic compounds in which an element other than carbon is present in the ring: Pyrrole Thiazole Furan Heterocyclic compounds containing nitrogen, oxygen, or sulfur are by far the most common. Tree important examples are given here in their Kekulé forms. These tree compounds are all aromatic * 1. Classification of heterocycles а) Five-membered heterocycles containing one heteroatom containing two heteroatoms (azoles) N O S Pyrrole Furan Thiophene N N N N N S Imidazole Pyrazole Thiazole * c) Six-membered heterocycles: containing one heteroatom containing two heteroatoms N O Pyridine Pyrane N N N N Pyrimidine Pyridazine N N Pyrazine * в) condensed heterocycles: Usually trivial names are used. Numeration of ring atoms begins with heteroatoms. Indole Quinoline Purine 1 N 1 N 1 N N 9 N N * AROMATICITY OF HETEROCYCLES Hückel’s rule N = 4n + 2 where is n (number of cycles) = 1,2, etc. N - number of conjugate -electrons Heterocyclic compounds have the aromatic properties, because its structure is a planar ring formed -bonds to the number of conjugated -electrons: * PYRIDINE NITROGEN Pyridine is basic in nature; it reacts with water and acids. The nitrogen atom is more electronegative as compared with the carbon itself. It pulls electron density from the ring. Therefore, the system with the pyridine nitrogen is called  -deficiency. Pyridine N The nitrogen atoms in the molecules of pyridine are sp2 hybridized. In pyridine the sp2–hybridized nitrogen donates one bonding electron located on the p orbital to the π system. This electron, together with one from each of the five carbon atoms, gives pyridine a sextet of electrons like benzene. The two unshared electrons of the nitrogen of pyridine are in an sp2 orbital that lies in the same plane as the atoms of the ring. This sp2 orbital does not overlap with the p orbitals of the ring. The unshared pair on nitrogen is not a part of the π system, and these electrons confer on pyridine the properties of a weak base. * Pyridine is  -deficiency sistem p-orbital is involved in conjugation sp2 - orbital lone pair of electrons Pyridine On the slade you can see electronic structure of pyridine and pair electrons which are outside of the cycle * Pyrrole is slightly acidic. The system with the pyrrole nitrogen is called  -excess. PYRROLE NITROGEN Pyrrol N In pyrrole the electrons are arranged differently. Because only four π electrons are contributed by the carbon atoms of the pyrrole ring, the sp2–hybridized nitrogen must contribute two electrons to give an aromatic sextet. Because these electrons are a part of the aromatic sextet, they are not available for donation to a proton. Thus, pyrrole is slightly acidic. * * Pyrrole is  -excess system p orbital lone pair of electrons involved in conjugation sp2 - orbital forms σ- bond Pyrrole And on the slade you can see two electrons which are a part of the aromatic sextet. * Pyridine nitrogen (basic properties) Pyrrole nitrogen (acidic properties ) AMPHOTERIC COMPOUNDS Imidazole Pyrazole One nitrogen atom in imidazole provides one electron to the conjugated system and, therefore, this is pyridic nitrogen. It imparts basic properties to imidazole. The second one provides two electrons to the conjugated system and is, therefore, pyrrolic nitrogen. This imparts weak acidic properties to imidazole. So, imidazole is amphoteric in nature. * * 3. Biologically important compounds with five-membered heterocycles Porphine - tetrapyrrole aromatic ring constructed of pyrroline (I), pyrrole (III) and two izopirrolnyh nuclei (II, IV), connected by a methine group = CH- Porphyrins (substituted porphine) - prosthetic groups of complex proteins: hemoglobin, myoglobin, mitochondrial respiratory enzymes - cytochrome, catalase and peroxidase, chlorophyll, vitamin B12. Porphine Porphyrine N N N N N N N N 14 * Pyrrole is the most important among five-membered cycles. Four pyrrole rings fused together constitute the flat macro cycle which is a component of porphyrins. Porphyrins are encountered in nature as complexes with metals. Complex of porphyrine with magnesium is in composition of chlorophyll. Complex of porphyrine with iron +2 is called heme which is prosthetic group of hemoglobin. Porphyrine is also contained in vit B12, cytochromes and some other enzymes. * USE IN MEDICINE Serotonin and tryptamine are biogenic amines, the products of the biochemical conversion of tryptophan in the body: Triptophan 5-hydroxy triptophan Serotonin Tryptamine N N N N * In medicine and pharmacology are used many condensed heterocyclic derivatives based on pyrrole - indole, namely the amino acid tryptophan and its conversion products - serotonin, tryptamine, indoxyl, -indoleacetic acid, and alakaloidy drugs. Serotonin and tryptamine are biogenic amines, the products of the biochemical conversion of tryptophan in the body: Tryptophan is an essential amino acid. Serotonin is a brain neuromediator. The disturbance of serotonin metabolism results in schizophrenia . * The final products of metabolism of serotonin and tryptamine in the body are: 5-hydroxy-  -indoleacetic acid and -indoleacetic acid 5-hydroxy-  -indoleacetic acid -indoleacetic acid N N * Serotonin is a physiologically active substance having the properties of neurotransmitter and hormone; regulates blood pressure, is a major modulator of human mental functions. In violation of serotonin associated with the development of schizophrenia, alcoholism, depression endogennnoy. Tryptamine exhibit toxic effects on the body. The final products of metabolism of serotonin and tryptamine in the body are: 5-hydroxy-  -indoleacetic acid and  -indoleacetic acid, which are excreted in the urine: * Five-membered heterocycles containing two heteroatoms (azoles): pyrazole, imidazole, and thiazole. Pyrazole Antipyrine Amidopyrine Analgin N N N N N N N N * Pyrazole (1,2 diazole) is a synthetic compound. Many derivatives of pyrazolone have been prepared and tested for antipyretic as well as for analgesic effects. Among these compounds antipyrine, amidopyrine (pyrimidon), and analgin have been very successful. * IMIDAZOLE Imidazole Histidine Purine N N N N N N N N The structure of the imidazole part of many biomolecules and drugs * Second one Five-membered heterocycles with two heteroatoms is imidazole. The structure of the imidazole part of many biomolecules and drugs, among which the most important are: proteinogenic amino acids histidine and purine heterocycle fused, which is part of many free nucleotides and nucleotide monomers of nucleic acids: Heterocyclic molecules (indol, imidazole, etc.) are included in some essential amino acids: e.g. tryptophan, histidine. * The main biologically active derivatives of imidazole are histidine and histamine N N N N * The main biologically active derivatives of imidazole are amino acid histidine and the product of its decarboxylation histamine. * In the organism Vitamine B1 is converted into its active form - thiamine pyrophosphate (TPP): N + N N S TPP * Third one Five-membered heterocycle with two heteroatoms is thiazole. Thiazole is in composition of Vitamine B1 (thiamine). Chemical structure of thiamine is composed of a pyrimidine ring and a thizole ring linked through a methylene bridging bond. In the organism Vitamine B1 is converted into its active form - thiamine pyrophosphate (TPP): * 4. Biologically important compounds with six-membered heterocycles: pyridine, pyrimidine, purine. Picolinic acid Nicotinic acid Isonicotinic acid N N N * Pyridine derivatives of biological significance are pyridine carboxylic acid: picolinic acid, nicotinic acid, isonicotinic acid. The most important of these are nicotinic acid and isonicotinic acid. * Derivative of nicotinic acid is nicotinamide (Vitamin PP) Cashews Peanuts Turkey meat Liver Tomatoes Никотиновая кислота и ее амид играют существенную роль в жизнедеятельности организма: они являются простетическими группами ферментов - кодегидразы I (дифосфопиридиннуклеотида - НАД) и кодегидразы II (трифосфопиридиннуклеотида - НАДФ), являющихся переносчиками водорода и осуществляющих окислительно-восстановительные процессы. Кодегидраза II участвует также в переносе фосфата. Недостаточность витамина РР у человека приводит к развитию пеллагры (болезни, обусловленной недостаточностью никотиновой кислоты /витамина РР/, триптофана и рибофлавина /витамина В2/). * * Nicotinamide (Vit PP(B5)) is a structural component and reactive site of the coenzyme NAD+ Nicotinamide Structure of nicotinamide adenine dinucleotide, oxidized (NAD+) * Nicotinic acid and its amide exhibit vitamin activity, they are used in medicine as antipellagric drugs. Nicotinamide (Vit PP(B5)) is a structural component and reactive site of the coenzyme NAD+ * ANTITUBERCULAR DRUG. Isoniazid Phthivazid N N * Physiologically important derivatives of isonicotinic acid are compounds used as medicines in tuberculosis treatment. Isonicotinic acid hydrazide is called isoniazid (tybazid). Isoniazid is a highly effective antitubercular drug Isoniazid condensed with vanilla has lower toxicity as compare to pure isoniazid. The product is called phthivazid, which is also a highly effective antitubercular drug. * Derivatives of pyrimidine called nitrogen bases. Uracil Thymine Cytosine N N N N N N * Second one Biologically important compound with six-membered heterocycles is pyrimidine. Derivatives of pyrimidine present in living systems are preferentially hydroxy- and aminopyrimidines which are in composition of nucleotides of nucleic acids, vitamins and coenzymes, so called nitrogen bases. * PYRIMIDINE DERIVATIVES Among the medicines - pyrimidine derivatives - important are preparations which are synthesized on the basis of barbituric acid * Trihydroxy form Trioxo form * Barbituric acid (2,4,6-trihydroxypyrimidine) in water solutions can exist being in some tautomeric forms: Lactam-lactim tautomerism, keto-enol tautomerism: N N N N Barbituric acid (2,4,6-trihydroxypyrimidine) is a basis for some medicines. Barbituric acid in water solutions can exist being in some tautomeric forms: Lactam-lactim tautomerism is caused by migration of hydrogen atom between NH- and carbonyl groups, keto-enol tautomerism is due to migration of hydrogen atom between methylene – CH2 - and carbonyl groups: * are drugs synthesized on the basis of barbituric acid. Phenobarbital (Luminal): R1 = C2H5; R2 = C6H5 Barbital (Veronal): R1 = R2 =C2H5 BARBITURATES N N * Barbiturates are drugs synthesized on the basis of barbituric acid. They are known to have hypnotic and sedative properties. Phenobarbital (Luminal): R1 = C2H5; R2 = C6H5 Barbital (Veronal): R1 = R2 =C2H5 * Purine – is a fused aromatic system consisting of pyrimidine and imidasole Hydroxy purines are formed in the organism in the nucleic acid metabolism: Purine Hypoxanthine Xanthine Uric acid 1 N 7 N N N N N N N N N N N N N N N 30 * Third one Biologically important compound with six-membered heterocycle is purine. Purine – is a fused aromatic system consisting of pyrimidine and imidasole Hydroxy- and amino purines participating in life activity processes are the most important purine derivatives. Hydroxy purines – hypoxanthine, xanthine and uric acid are formed in the organism in the nucleic acid metabolism. * TAUTOMERISM For purine containing compounds lactim-lactam tautomerism is typical (prototropic tautomerism): Lactim-lactam tautomerism of hypoxanthine Prototropic tautomerism of hypoxanthine N N N N N N N N N N N N * For purine containing compounds lactim-lactam tautomerism is typical, as well as migration of hydrogen proton between nitrogen atoms at positions 7 and 9 of imidazole ring (prototropic tautomerism): * Uric acid is dibasic, poorly soluble in water, but well soluble in bases with formation of acidic and neutral salts – urates: URIC ACID N N N N N N N N N N N N H * Uric acid is the end product of purines metabolism in the organism. The average urinary excretion of uric acid is about 0.5-1 g per day. Uric acid is dibasic, poorly soluble in water, but well soluble in bases with formation of acidic and neutral salts – urates * IMPORTANT HETEROCYCLIC COMPOUNDS OF AMINOPURINES 6-aminopurine (adenine) 2-amino-6-hydroxypurine (guanine) * IMPORTANT HETEROCYCLIC COMPOUNDS OF AMINOPURINES are: 6-aminopurine (adenine) and 2-amino-6-hydroxypurine (guanine), which are the most important purines as they are components of nucleic acids. * NUCLEIC ACIDS Were discovered in 1868 by Swiss chemist F. Miescher First found in the nucleus Friedrich Miescher * * The role of nucleic acids People, animals, plants, and more all are connected by genetic material. Every living thing may look different and act different, but deep down — way deep down in the nucleus of cells — living things contain the same chemical “ingredients” making up very similar genetic material. * 5. The structure and biochemical functions of nucleosides and nucleotides nucleic acid The structure of nucleic acids, monosaccharides are included in the β - furanose form: * Nucleic acids are biological polymers comprised of monomeric units called nucleotides. The structure of nucleic acids, monosaccharides are included in the β - furanose form: DNA is the molecule responsible for the storage of genetic information * SUGAR Ribose 2’ There are two types of nucleic acid: RNA and DNA. Structure of RNA include ribose * SUGAR deoxyribose 2’ H 2’ - And structure of DNA include deoxyribose * NITROGEN BASES HN HN N N 1 N N 5 The nucleosides that can be obtained from DNA all contain 2-deoxy-D-ribose as their sugar component and one of four heterocyclic bases, adenine, guanine, cytosine, or thymine. The nucleosides obtained from RNA contain D-ribose as their sugar component and adenine, guanine, cytosine, or uracil as their heterocyclic base. * LACTIM-LACTAM TAUTOMERISM Lactam form Lactim form * Nitrogen bases show lactim-lactam tautomerism but in the composition of nucleic acids nitrogen bases exist only being in lactam form. * NUCLEOSIDES The heterocyclic base of a nucleotide is attached through an N-glycosidic linkage to C1’ of the ribose or deoxyribose unit and this linkage is always β. The phosphate group of a nucleotide is present as a phosphate ester and may be attached at C5’ or C3’. (In nucleotides, the carbon atoms of the monosaccharide portion are designated with primed numbers, i.e. 1’, 2’, 3’, etc.) Removal of the phosphate group of a nucleotide converts it to a compound known as a nucleoside. * NUCLEOSIDES The nucleosides that can be obtained from DNA all contain 2-deoxy-D-ribose as their sugar component and one of four heterocyclic bases, adenine, guanine, cytosine, or thymine. The nucleosides obtained from RNA contain D-ribose as their sugar component and adenine, guanine, cytosine, or uracil as their heterocyclic base. * NAMING OF NUCLEOSIDES In naming of nucleosides have suffix : -idine for pyrimidine bases: (uridine (U), thymidine (Т), cytidine (C), deoxycytidine (dC)), -osine for purine bases: аdenosine (А), deoxyаdenosine (dА), guanosine (G), deoxyguanosine (dG). In naming of nucleosides pyrimidine bases have suffix –idine and purine bases have suffix –osine. * * NUCLEOTIDES 1’ 3’ 5’ * The position of the phosphate group is sometimes explicitly noted by use of the names uridine 5’-monophosphate or 5’-uridylic acid. Nucleotides are named in several ways. Uridylic acid is usually called UMP, for uridine monophosphate, although it can also be called uridine 5’-monophosphate or 5’-uridylic acid. If a nucleotide is present as a diphosphate or triphosphate, the names are adjusted accordingly, such as ADP for adenosine diphosphate or GTP for guanosine triphosphate. * Nikotinamidnukleotide NAD+ nicotinamide adenine dinucleotide NAD+, nicotinamide adenine dinucleotide, one of the most important coenzymes in biological oxidations and reductions, includes both a pyridine derivative (nicotinamide) and a purine derivative (adenine) in its structure. NAD+ is the oxidized form that contains the pyridinium aromatic ring. The reduced form of the coenzyme is NADH, in which the pyridine ring is no longer aromatic due to presence of an additional hydrogen and two electrons in the ring. A key role of NAD+ in metabolism is to serve as a coenzyme for enzymes called dehydrogenases in glycolysis and then in Krebs cycle, the pathways by which nutrients are broken down for energy produc­tion. When glucose in glycolysis and acetyl-CoA are oxidized concurrently the NAD+ is reduced to its higher energy form, NADH. * ATP adenosine triphosphate ribonucleotide macroergic bonds Adenine ATP – Adenosine triphosphate The chemical energy stored in NADH is used in the mitochondria for the production of ATP. The 5’- triphosphate of adenosine is the important energy source. ATP is a nucleotide consisting of adenine, ribose and three molecules of phosphate. * cAMP cyclic adenosine monophosphate Cyclic AMP Another important nucleotide is cAMP Cyclic adenosine monophosphate. This is an important regulator of hormone activity. cAMP is a universal “second messenger” between the hormones and various functions of the cells susceptible to the action by these hormones. * Primary structure of DNA 1’ 2’ 3’ 4’ 5’ DNA consists of nucleotides linked by phosphate ester linkages. Phosphate esters link the 3’(стрек)–OH of one ribose (or deoxyribose) with the 5’(стрек) –OH of another. It is the base sequence along the chain of DNA that contains the encoded genetic information. * THE STRUCTURE OF DNA Erwin Chargaff 1950 Chargaff's rule Chargaff's rules states that DNA from any cell of all organisms should have a 1:1 ratio (base Pair Rule) of pyrimidine and purine bases and, more specifically, that the amount of guanine is equal to cytosine and the amount of adenine is equal to thymine. This pattern is found in both strands of the DNA. They were discovered by Austrian chemist Erwin Chargaff. * Фрэнсис Крик Джеймс Уотсон 1953 Open structure of DNA Explanation Chargaff’s rule gave Watson and Crick. Watson and Crick proposed a double helix as a model for the secondary structure of DNA. According to this model, two nucleic acid chains are held together by hydrogen bonds between base pairs on opposite strands. * Francis Harry Compton Crick James Dewey Watson Nobel Prize 1962 In 1962, Watson and Crick received the Nobel Prize. * Specific base pairing means that two chains of DNA are complementary. G C A T - - - - - - - - - - - - stronger Hydrogen bonds are weak!!! Watson and Crick proposed a double helix as a model for the secondary structure of DNA. According to this model, two nucleic acid chains are held together by hydrogen bonds between base pairs on opposite strands. Base pairing occurs in only a specific way: adenine (A) with thymine (T) and cytosine (C) with guanine G). Adenine is linked with Ttymine by means of two bonds, Cytosine with Guanine by three bonds. Specific base pairing means that two chains of DNA are complementary. * 5’ C 3’ 5’ Т ОН 3’ A 3’ ОН 5’ Т A НО G On this slade you can see bonds between adenine and thymine $ guanine and cytosine * DNA composition Specific base pairing means that two chains of DNA are complementary. Wherever Adenine appears in one chain, Thymine must appear opposite it in the other; wherever Cytosine appears in one chain, Guanine must appear in the other. * THE PRINCIPLE OF THE STRUCTURE OF DNA А G G Т C А А C Irregularity Double-stranded C C Complementary А G Т Т G Antiparallel 3' 5' 5' 3' Т * WHAT IS THE DIFFERENCE BETWEEN RNA AND DNA ? The structure of RNA is a single strand structure and DNA - double helix; Main component of RNA is ribose and DNA is dioxyribose; Pyrimidine base of RNA is uracil and pyrimidine base of DNA is thymine. * RNA Purines Pyrimidines CH uracil (U) * Purines Pyrimidines DNA * * TYPES OF RNA transfer RNA (tRNA) - transporting of amino acids into the ribosome; messenger RNA (mRNA) - is a matrix for protein synthesis; ribosomal RNA (rRNA) - takes part in protein synthesis in ribosome. * The formation of RNA secondary structure G C C U U C G G A A G U A U C A U A * Scheme formation of loops RNA using the complementary pairs * * «cloverleaf» Transfer RNA (tRNA) ~ 100 nucleotides anticodon Aminoacid * Ribosomal RNA (rRNA) The largest of RNA from all types of RNA. It has about 2-3 thousand nucleotides * RNA DNA Protein * N H a b b a 1 2 3 4 5 S N 1 2 4 3 5 H H N S Имидазол Тиазол N N Пиразол N N H N a b a b 1 2 3 4 5 O 1 2 3 4 5 S 1 2 3 4 5 Furan Pyrrole Thiophene N a b a b 1 6 2 3 4 5 Пиридин g O a b a b Ïèðàí g N 1 6 2 3 4 5 Пиримидин N N 1 6 2 3 4 5 Пиридазин N N 1 6 2 3 4 5 Пиридазин N H H 1 6 2 3 4 5 Индол N 7 8 9 6 4 5 8 9 10 N 1 2 3 7 Хинолин 1 6 2 3 4 5 N 7 8 9 N N N Пурин H N a b a b 1 2 3 4 5 O 1 2 3 4 5 S 1 2 3 4 5 Пиррол Фуран Тиофен H H H H R R R R R R R R N N N N I II III VI N N N N I II III VI Порфин Порфирин H C H 2 C H C O O H N H 2 H C H 2 C H N H 2 H O C H 2 C H 2 N H 2 C O O H H C H 2 C H 2 N H 2 H H O N N N N - CO 2 5-гидрокситриптофан Триптамин Серотонин Триптофан H H O C H 2 C O O H H C H 2 C O O H N N 5-окси- b -èíäîëèëóêñóñíàÿ êèñëîòà b -èíäîëèëóêñóñíàÿ êèñëîòà H C 6 H 5 О C H 3 C H 3 C 6 H 5 О C H 3 C H 3 ( C H 3 ) 2 N C 6 H 5 О C H 3 C H 3 N C H 3 C H 2 N a S O 3 N Пиразол N N N N N N N Антипирин Амидопирин Анальгин H H C H 2 C H C O O H H N H 2 N Имидазол N N N N N N N Гистидин Пурин H C H 2 C H C O O H N H 2 H C H 2 C H 2 N H 2 N N Histidine - ÑÎ 2 N N Histamine H 3 C N H 2 C H 2 C H 3 C H 2 C H 2 O P O O H O P O O H O N N S N + _ C O O H C O O H C O O H N .. N .. N .. C О N H 2 N H C О N N H C H O H N N OCH 3 Изониазид Фтивазид O H H O O H H O C H 3 N H 2 H O N N N N N N Урацил Тимин Цитозин O O O H N N R 1 R 2 H H O H H O H O H H O H O O H N N N N N N N N N N N N Гипоксантин Ксантин Мочевая кислота H O H H 2 N H O H 2 N Н H O H 2 N Н N N N N Лактам-лактимная таутомерия гипоксантина N N N N N N N N Прототропная таутомерия гипоксантина H O Н O H O H O Н O H O N a H O Н N a O O N a N N N N + NaOH - H 2 O N N N N + NaOH - H 2 O N N N N + NaOH - H 2 O N N N N N H 2 H N N N N О Н H H 2 N 1 2 3 4 5 6 7 8 9 Аденин Гуанин O H H O H H H O H H O H H O H H O H H C H 2 H O C H 2 H O O H b - D-deoxyribofuranose b - D-ribofuranose O O C H 3 N H 2 H O O O H H N HN N N N Uracil Thymine Cytosine 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 2,4-dioxopyrimidine 5-methyl-2,4-dioxopyrimidine 4-amino-2-oxopyrimidine HN N N N N N H 2 H N N N N H H H 2 N O 1 2 3 4 5 6 7 8 9 Adenine Guanine 1 2 3 4 5 6 7 8 9 6-aminopurine 2-amino-6-oxopurine H H N N O O N N O H H O lactam form lactim form N N N N N H 2 O H H O H H O H H H O H 2 C N N N N N H 2 O H H O H H H H H O H 2 C Adenosine 2'-Deoxyadenosine O N O N O H H H O H H O H C H 2 O H H P O H O H O H O - H 2 O O N O N O H H H O H H O H C H 2 H O P O H O H O + Uridine Uridylic acid 5' 5' N C O N H 2 O H H O H H O H H N N N N N H 2 O H H O H H O H H C H 2 O P O O P O O H O H O C H H N H H R + + H + , 2e _ NAD + NADH N N N N N H 2 O H H O H O H H C H 2 O H P O O Cyclic ÀÌP O O O O O O O O А Т 3' 5' 3' 5' 3' 5' C G Т А 5' 5' 5' 3' 3' 3' 5' 3' G C 3' 5' Monosaccharides Phosphates Heterocyclic bases P P P P P P