Nucleotide chemistry.pptx

nucleotide chemistry for medical students

1. Nucleotide chemistry

2. Nucleotide = pentose + base + phosphate Nucleoside = pentose + base

3. Major bases BASE NUCLEOSIDE NUCLEOTIDE PURINES Adenine Adenosine AMP Guanine Guanosine GMP Oxopurines Hypoxanthine Inosine IMP Xanthine xanthosine XMP Pyrimidines Cytosine Cytidine CMP Thymine Thymidine TMP Uracil Uridine UMP

4. Minor bases Base Use Purines 7-methyl Guanine RNA Caffeine (Coffee) Diuretics CNS stimulators Doesn’t produce uric acid Theophylline(Tea) Theobromine(cocoa) pyrimidines Dihydrouracil 5-Methylcytosine Uric acid: end product of purine catabolism excreted in urine level in blood is 3 to 7 mg/ dL Gout is a disease characterized by high levels of plasma uric acid (hyperuricemia).

5. Adenine nucleotides AMP,ADP,ATP Storage of energy(2 high energy bonds 1. αβ 2. βγ ) cAMP 2ry messenger( ATP adenylyl cyclase cAMP phoshodiesterase AMP) PAPS Sulphur containing compounds (1.GAGs 2.sulpholipids)

6. Adenine nucleotides Coenzymes Hydrogen carriers NAD & NADP FAD Acyl group carrier Coenzyme A ( coA ) N.B FMN is a hydrogen carrier that doesn’t contain Adenine S- Adenosyl methionine ( Active Methionine) or (SAM) is a nucleoside and methyl donor

7. Guanine Nucleotides GMP, GDP, GTP cGMP 2ry messenger( G TP gyaneylyl cyclase cGMP phoshodiesterase GMP) may be antagonistic to cAMP . vasodilators ( smooth muscle relaxation ) nitric oxide.

8. Cytosine Nucleotides CMP, CDP, CTP CDP-choline, CDP-ethanolamine or CDP- diacylglycerol Phospholipid synthesis

9. Uracil Nucleotides UMP, UDP, UTP - UDP- Glc is used for synthesis of glycogen, glycoproteins and glycolipids . - UDP-Gal is used for synthesis of lactose, glycoproteins and glycolipids . - UDP- glucuronic acid active form of glucuronic acid synthesis of GAGs conjugation reactions with steroids, bile pigments and some drugs.

10. 2ry Messengers cAMP DAG & IP3

11. 2ry Messengers DAG &IP3 activation of G proteins activation of phospholipase C. PIP2 phospholipase C DAG+IP3 IP3 Calcium DAG and Caicium activates protein kinase C (PKC) phosphorylation of certain proteins. Examples chemical transmitters acetylcholine , histamine and serotonin), hormones vasopressin and α-1 receptors growth factors cAMP activation of G proteins activation of adenylyl cyclase cAMP activates the protein kinase A phosphorylation of proteins It can be reversed by Phosphatase ( dephosphorelation ) Phophodiesterase ( cAMP ) Examples insulin&glucagon

12. Nucleic acid chemistry

13. Genetic Terminology 1- Genes: Classically a gene is a unit of the DNA that encodes a particular protein or RNA molecule. Chemically , a gene is a sequence of nucleotides along a DNA molecule. Most eukaryotic genes are discontinuous i.e. coding sequences ( exons or expressed sequences ) separated by noncoding sequences ( introns ). 2- Chromosomes: Chromosomes : genes which are arranged in linear orders Locus of the gene : is the position of a gene along a chromosome Each cell contains two copies of each type of chromosomes (one inherited from the mother and one inherited from the father).

14. Genetic Terminology 3-genome: It is the total genetic information presented by the group of chromosomes in any cell. The human haploid genome consists of 23 chromosomes with a total of three billion base pairs (3 x 109 bp ), contains about 30,000 to 50,000 genes . 4- genotype and phenotype: The genotype is the set of genes in our DNA which is responsible for a particular trait. The phenotype is the physical or biochemical expression of that trait. E.G. Skin color, hair color, height, weight, behavior and some diseases like diabetes mellitus. Homozygous: if the two genes (alleles) at certain locus in an individual are identical Heterozygous . If the two genes are different from each other.

15. DNA

16. I- DNA Primary Structure : The nucleotides are linked together by phosphodiester bonds, Free phosphate group attached to 5`- hydroxyl group, free 3`- hydroxyl group. The order of nucleotides in any DNA strand is always written in the 5` to 3` direction.

17. II- DNA Secondary Structure : Double Helix (dsDNA) Two antiparallel strands form a right-handed helix. Complementary base pairing : if Adenine is 20% then Cytosine is ??? Base stacking : hydrogen bonding between complementary base pairs Van der Waals forces and hydrophobic interactions of stacked base pairs provide the stability of the double helix. Dimensions The B-form of DNA is 2 nm wide . major groove (2.2 nm) minor groove (1.2 nm) .

18. Denaturation of DNA Heating of DNA produces rupture of hydrogen bonds and separation of the two strands of DNA or DNA denaturation . Cooling of denatured DNA results in reformation of the double helix or renaturation or reannealing .

19. DNA Tertiary Structures Supercoiling may be positive (more tight) or negative (less tight ). Negative supercoils are more commonly present under normal physiological state.

20. DNA Tertiary Structures Linear Circular Site Eukaryotes Prokaryotes Mitochondria in eukaryotes Types of supercoiling a) Toroidal: The DNA may coil into a series of spirals around a cylinder-shaped object. b) Interwound coil: The DNA may also cross over and under itself repeatedly. a) Right-handed supercoil. b) Left-handed supercoil.

21. Structure of chromatid: 1- A single DNA molecule 2- Histone proteins 5 main types ( H1 , H2A, H2B, H3 and H4) + ve charged rich in lysine & arginine In contact with minor groove in DNA N.B chromatid is formed of many nucleosomes. nucleosome is formed of: 8 histone ptns (2 copies of H2A, H2B, H3 and H4 ) 1¾ toroidal supercoiled DNA segment ( contains average 140 bp ). Linker or spacer DNA (contains average 60 bp ) H1 is attached to linker DNA.

22. Structure of chromatid: 3- Non-histone proteins: They interact with the major groove Function : important for regulation of gene expression responsible for replication and transcription. Kinetochore : centromere(rich in A…T Bases) connected to specific proteins. Connected to mitotic spindle Telomere

23. Supercoiling of DNA The length of human DNA per cell is approximately 2 meters, and D iameter of the nucleus is 10 microns. S tructure about 10 m icron long and 1 m icron diameter

24. Mitochondrial DNA ( mtDNA ) 0.3 to 1% of the total cellular DNA . responsible for controlling synthesis of 2 rRNA , 22 tRNA and 13 proteins . proteins are involved in oxidative phosphorylation (electron transport chain and ATP synthesis). maternally inherited certain types of myopathies .

25. RNA

26. A) Transfer RNAs ( tRNAs ) Smallest 15% percent of the total RNA Unusual bases (e.g. Dihydrouracil ) this leads to characteristic secondary and tertiary structure ( clover leaf appearance ). Carries its specific amino acid to the site of protein synthesis.

27. Transfer RNA is coiled to form a cloverleaf appearance with five main arms: 1- The acceptor arm: It terminates at its 3`OH end by a specific sequence formed of CCA. It carries the amino acid 2- D arm: It contains the unusual base dihydrouracil . D-arm is important for recognition of tRNA by aminoacyl- tRNA synthetase enzyme which catalyzes binding of a specific amino acid to its specific tRNA .

28. Transfer RNA is coiled to form a cloverleaf appearance with five main arms: 3- Anticodon arm: It contains three specific bases known as the anticodon. This portion of tRNA plays a key role in translation by pairing with the complementary codon of mRNA and helps in placing each amino acid in its proper site in the polypeptide chains of proteins. 4- Extra arm: It contains from 3 to 12 bases and it is the major site for variation in tRNA .

29. Transfer RNA is coiled to form a cloverleaf appearance with five main arms: 5- T ψ C arm (or loop IV) contains the unusual specific sequence of thymine and pseudouridine bases. Pseudouridine (C1` of ribose attached to C5 of uracil ) This arm is important for binding of tRNA to the ribosome during the process of protein synthesis.

30. B) Messenger RNAs (mRNAs) 5 % of the RNA It consists of: Coding region Initiation codon Coding area Stop codon Non coding region 5 Cap Poly A tail

31. B) Messenger RNAs (mRNAs) Monocistronic mRNA : It carries information from just one gene. It contains one initiation codon and one termination codon and is characteristic of eukaryotes. - Polycistronic mRNA : It contains multiple initiation and multiple termination codons and is characteristic of prokaryotes

32. C)Ribosomal RNAs ( rRNAs ) In prokaryotic cells. The fully active 70S ribosomes : 50S subunit 30S subunit. The rRNA forms about 80% of total RNA of the cell. Svedberg unit (sedimentation or S unit) is a measure of the sedimentation velocity by high speed centrifuge, which depends on the molecular weight as well as the size of the particles i.e. particle density.

33. C)Ribosomal RNAs ( rRNAs ) In Eukaryotic cells The fully active 80S ribosomes 60S subunit 5S RNA 5.8S RNA 28S RNA 50 proteins 40S subunit 18S RNA. 30 proteins.

34. D) Other Forms of RNA (Noncoding RNA): In addition to the major three types of RNA, small RNA species are found in eukaryotic cells. They include: - Small nuclear RNAs ( snRNAs ): It is involved in mRNA processing. - Micro RNAs (miRNAs): It plays an important role in regulation of gene expression.

35. Prokaryotic DNA and Chromosomes Prokaryotic organisms include bacteria and blue-green algae. Each cell contains one single double-stranded supercoiled circular chromosome and has no nuclear membrane . The chromosome is associated with histone-like proteins. Plasmid DNA carries genetic information and undergoes replication that may or may not be synchronized to chromosomal division. Plasmids may carry genes that convey antibiotic resistance to the host bacterium.