Terminators

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Terminators

  1. 1. NUCLEIC ACID METABOLISM • PRESENTED BY TERMINATORS  MANTHAN VORA  MITUL PATEL  PRATHMESH TIKARE  PRAJAKTA MORE  PRACHI DIKONDWAR  KAPIL BAISANE  BHAGYASHREE RELEKAR  VINU JOHN  ASHMITA PAGARE
  2. 2. Nucleic acids
  3. 3. Introduction  Definition  Functions  Component of nucleic acids
  4. 4. Definition  Any of a group of complex compounds found in all living cells and viruses, composed of purines, pyrimidines, carbohydrates, and phosphoric acid.  Two forms of nucleic acids :• DNA (deoxyribonucleic acid ) • RNA (ribonucleic acid )
  5. 5. Functions  Functions of DNA:• A permanent storage place for genetic information. • Controls the synthesis of RNA. • Determines the protein development in new cells.
  6. 6.  Functions of RNA :• • • • • Messenger RNA (m RNA ) Ribosomal ( rRNA) Transfer (tRNA) In post transcription modify the other RNA’s Transfer genetic information
  7. 7. Component of nucleic acids Nucleic acids are build up by the monomeric units -nucleotides that have a pentose sugar, nitrogen base, and phosphate Base PO4 Sugar nucleoside Nucleoside + Phosphate = Nucleotide
  8. 8. Function of nucleotides • Build blocks or monomeric units • Structural component of several coenzymes of Bcomplex vitamins. e.g. FAD. Coenzyme A • Serve as intermediates in biosynthesis of carbohydrate, lipid & protins. e.g. S-adenosylmethionine • Control several metabolic reaction.
  9. 9. Structure of Nucleotides Nitrogen-Containing Bases (Purines &pyrimidines) O NH 2 N N N N H O NH 2 thymine (T) NH 2 N N N N H guanine (G) N H H adenine (A) O H CH 3 N CH 3 N O N H cytosine (C) O H O CH 3 N N H uracil (U) Structure of purine (A,G) & pyrimidines (C, T, U)
  10. 10.  Sugars HOCH2 O OH ribose OH OH HOCH2 O OH OH (no O) deoxyribose
  11. 11. Nucleosides in DNA Base Adenine (A) Sugar Deoxyribos Nucleoside Adenosine Guanine (G) Deoxyribose Guanosine Cytosine (C) Deoxyribose Cytidine Thymine (T) Deoxyribose Thymidine
  12. 12. Nucleosides in RNA Base Sugar Nucleoside Adenine (A) ribose Adenosine Guanine (G) Cytosine (C) Uracil (U) ribose Guanosine Cytidine Uridine ribose ribose
  13. 13. Nucleoside di and triphosphate Adenosine 5’ monophosphate Thymidine 5’ monophosphate
  14. 14. Different form of DNA double helix • DNA exist in at least 6 different form-A to E and Z • B-form of DNA double helix described by Watson ad crick. • B-form has 10 base pairs spanning a distance of 3.4nm.ad width of double helix is 2nm.
  15. 15. The size of DNA • DNA huge in size. • B-DNA with a thickness of 0.34nm • Molecular weight 660. • The term kilo base paire [kb=1000 base paire] is commonly used in the DNA structure.
  16. 16. THE WASTON AND CRICK MODEL OF DNA
  17. 17. • James Watson (American biologist) and Frances Crick (English chemist) proposed Model of DNA to explain its structure in 1953 • DNA is right handed double helix . Consists of two polydeoxyriboncleotide chains • Two strands are anti parallel • Diameter of double helix is 2 nm • Two polynucleotide chains complementary to each • A – T pair has 2 hydrogen bonds while G – C pair has 3 hydrogen bonds • Major grooves and minor grooves .
  18. 18. RNA The RNAs are synthesized by DNA,and are primarily involved in protein synthesis. It is the polymer of polynucleotide held together by 3,5phosphodiester bridge.
  19. 19. How RNA different from DNA • Pentose- The suger in RNA is ribose in DNA it is deoxyribose. • Pyrimidine- RNA contain Uracil while in DNA it is thymine. • Single strand- RNA is single stranded nucleotides and in DNA it may be folded or double stranded.
  20. 20. Types of RNA • Messenger RNA ( mRNA ) • Transfer RNA ( tRNA ) • Ribosomal RNA ( rRNA )
  21. 21. Messenger RNA ( mRNA ) • It synthesized in nucleus as heterogeneous nuclear RNA and on processing it liberates functional mRNA. • It has high molecular weight with short half life. • It carries the information from DNA to the Ribosome i.e. the site of protein synthesis. • coding sequence of mRNA determines the amino acid sequence in proteins.(4-5%)
  22. 22. Transfer RNA ( tRNA ) • tRNA contains 71-80 nucleotides (mostly75) • 20 species of tRNAs as 20 amino acids present the protein structure. • Structure -- clover leaf
  23. 23. • Accepter arm •Anticodon arm •D arm •T C arm •The variable arm
  24. 24. Ribosomal RNA ( rRNA ) • Protein synthesis takes place. • It is the catalytic component of the ribosomes.
  25. 25. RNAs and their functions Types of RNA Abbreviation Function Messenger RNA mRNA Trancfer of genetic information from genes to ribosomes to synthesis proteins Transfer RNA tRNA Transfer amino acid to mRNA for protein synthesis Ribosomal RNA rRNA Provide structural framework for ribosomes. Small nuclear RNA snRNA Involved in mRNA processing Small cytoplasmic RNA scRNA Involved in selection of protein for export
  26. 26. Replication of DNA
  27. 27. • What is DNA? • What is Replication?
  28. 28. Important features of DNA replication • DNA replication is Semiconservative. (First experiment evidence was provided by Mathew Meselson and Franklin Stahl in 1958.) • Replication begins at the origin and usually proceeds bidirectionally. • DNA synthesis proceeds in 5’ to 3’ direction. • DNA synthesis is semidiscontinous.
  29. 29. • Replication fork: • Single stranded DNA binding (SSB) proteins: • Lagging strand: • Leading strand: • Okazaki pieces: • RNA primer: • Enzymes: Helicase polymerase
  30. 30. DNA replication:
  31. 31. Process:
  32. 32. Life cycle:
  33. 33. Transcription - Bhagyashree Relekar
  34. 34. Transcription: overview • In prokaryotes transcription and translation are coupled. • In eukaryotes transcription and translation are separated. Transcription occurs in the nucleus, and translation occurs in the cytoplasm on ribosomes.
  35. 35. Stages of Transcription • Chain Initiation • Chain Elongation • Chain Termination
  36. 36. TRANSLATION  genetic code : composed of 4 nucleotide bases.  Produce 64 different combination of codon.  Termination codons - UAA,UAG and UGA.  Initiating codon – AUG (Met) , GUG (Val).
  37. 37. Protein Synthesis  It occurs in three stages1. Requirement of the components  Amino acids  Ribosome  m RNA  t RNA  Energy sources 2. Activation of amino acids –  Aminoacyl-tRNA synthetase  Corresponding t-RNA
  38. 38. 3. Protein synthesis proper  Initiation :  Elongation :  Termination :
  39. 39. Nucleotides: Synthesis and Degradation
  40. 40. Nucleic Acid Bases Derived from purine or pyrimidine Purines Pyrimidines
  41. 41. Sugars D-Ribose and 2’-Deoxyribose *Lacks a 2’-OH group
  42. 42. Nucleosides • Result from linking one of the sugars with a purine or pyrimidine base through an Nglycosidic linkage
  43. 43. Nucleosides
  44. 44. Nucleotides • Result from linking one or more phosphates with a nucleoside onto the 5’ end of the molecule through esterification
  45. 45. Nucleotides • RNA (ribonucleic acid) is a polymer of ribonucleotides • DNA (deoxyribonucleic acid) is a polymer of deoxyribonucleotides • Both deoxy- and ribonucleotides contain Adenine, Guanine and Cytosine – Ribonucleotides contain Uracil – Deoxyribonucleotides contain Thymine
  46. 46. Nucleotides • Monomers for nucleic acid polymers • Nucleoside Triphosphates are important energy carriers (ATP, GTP) • Important components of coenzymes – FAD, NAD+ and Coenzyme A
  47. 47. Naming Conventions • Nucleosides: – Purine nucleosides end in “-sine” • Adenosine, Guanosine – Pyrimidine nucleosides end in “-dine” • Thymidine, Cytidine, Uridine • Nucleotides: – Start with the nucleoside name from above and add “mono-”, “di-”, or “triphosphate” • Adenosine Monophosphate, Cytidine Triphosphate, Deoxythymidine Diphosphate
  48. 48. Nucleotide Metabolism • PURINE RIBONUCLEOTIDES: formed de novo – i.e., purines are not initially synthesized as free bases – First purine derivative formed is Inosine Mono-phosphate (IMP) • The purine base is hypoxanthine • AMP and GMP are formed from IMP
  49. 49. Purine Nucleotides • Get broken down into Uric Acid (a purine) N1: Aspartate Amine C2, C8: Formate N3, N9: Glutamine C4, C5, N7: Glycine C6: Bicarbonate Ion
  50. 50. Purine nucleotide Synthesisoverview
  51. 51. Purine Nucleotide Synthesis OOC 2- O3P O CH2 H O H α H H OH OH C OH ATP O3P O CH2 O H ADP + Pi HC N H CH2 C N SAICAR Synthetase AIR Car boxylase ADP + Pi COO H OH O O Ribose-5-Phosphate Fumarate P O O P O C O 5 O C C 5-Aminoimidazole Ribotide (AIR) ADP + Pi AIR Synthetase Glutamine + H2O Amidophosphoribosyl Transferase H O NH2 OH OH HN H ADP + Pi H O NH2 NH O H Glycinamide Ribotide (GAR) GAR Transformylase N NH Ribose-5-Phosphate 5-Formaminoimidazole-4-carboxamide ribotide (FAICAR) IMP Cyclohydrolase O C N HN C O C THF CH 5 CH H2C N10-Formyl-THF C H ATP + Glutamine + H2O HC C5 NH H OH C H 2O H N C H OH ADP + Glutamate + Pi FGAM Synthetase GAR Synthetase O O Formylglycinamidine ribotide (FGAM) N C4 NH Ribose-5-Phosphate Formylglycinamide ribotide (FGAR) AICAR Transformylase THF C H2N Ribose-5-Phosphate Glycine + ATP H 2C CH O β-5-Phosphoribosylamine (PRA) O3P O CH2 N10-FormylTHF O C β H H 2- 5-Aminoimidazole-4-carboxamide ribotide (AICAR) H N H2 C O3P O CH2 N Ribose-5-Phosphate ATP Glutamate + PPi 2- CH 5 H2N Ribose-5-Phosphate 5-Phosphoribosyl-α-pyrophosphate (PRPP) N C4 N H2N Adenylosuccinate Lyase O H2N CH N 5-Aminoimidazole-4-(N-succinylocarboxamide) ribotide (SAICAR) N HC 4 CH 5 H2N ATP +HCO3 H α N C4 Ribose-5-Phosphate Ribose Phosphate Pyrophosphokinase H OH 5 Carboxyamidoimidazole Ribotide (CAIR) AMP 2- Aspartate + ATP CH H2N α-D-Ribose-5-Phosphate (R5P) C N C4 O COO 4 CH N N 2- O3P O CH2 H H OH O H H OH Inosine Monophosphate (IMP)
  52. 52. IMP Conversion to AMP
  53. 53. IMP Conversion to GMP
  54. 54. Purine Catabolism and Salvage Nucleoti dase Deamina se Phosphor ylas,Oxid ase Xazanthin e oxydase Phosphor ylase Guana se
  55. 55. What Happened to the toe? Why is it swollen?
  56. 56. A CASE STUDY : GOUT • • • A 45 YEAR OLD MAN AWOKE FROM SLEEP WITH A PAINFUL AND SWOLLEN RIGHT GREAT TOE. ON THE PREVIOUS NIGHT HE HAD EATEN A MEAL OF FRIED LIVER AND ONIONS, AFTER WHICH HE MET WITH HIS POKER GROUP AND DRANK A NUMBER OF BEERS. HE SAW HIS DOCTOR THAT MORNING, “GOUTY ARTHRITIS” WAS DIAGNOSED, AND SOME TESTS WERE ORDERED. HIS SERUM URIC ACID LEVEL WAS ELEVATED AT 8.0 mg/dL (NL < 7.0 mg/dL). THE MAN RECALLED THAT HIS FATHER AND HIS GRANDFATHER, BOTH OF WHOM WERE ALCOHOLICS, OFTEN COMPLAINED OF JOINT PAIN AND SWELLING IN THEIR FEET.
  57. 57. A CASE STUDY : GOUT • THE DOCTOR RECOMMENDED THAT THE MAN USE NSAIDS FOR PAIN AND SWELLING, INCREASE HIS FLUID INTAKE (BUT NOT WITH ALCOHOL) AND REST AND ELEVATE HIS FOOT. HE ALSO PRESCRIBED ALLOPURINOL. • A FEW DAYS LATER THE CONDITION HAD RESOLVED AND ALLOPURINOL HAD BEEN STOPPED. A REPEAT URIC ACID LEVEL WAS OBTAINED (7.1 mg/dL). THE DOCTOR GAVE THE MAN SOME ADVICE REGARDING LIFE STYLE CHANGES.
  58. 58. Uric Acid Excretion • Humans – excreted into urine as insoluble crystals • Birds, terrestrial reptiles, some insects – excrete insoluble crystals in paste form – Excess amino N converted to uric acid • (conserves water) • Others – further modification : Uric Acid  Allantoin  Allantoic Acid  Urea  Ammonia
  59. 59. Gout • Impaired excretion or overproduction of uric acid • Uric acid crystals precipitate into joints (Gouty Arthritis), kidneys, ureters (stones) • Lead impairs uric acid excretion – lead poisoning from pewter drinking goblets – Fall of Roman Empire? • Xanthine oxidase inhibitors inhibit production of uric acid, and treat gout • Allopurinol treatment – hypoxanthine analog that binds to Xanthine Oxidase to decrease uric acid production
  60. 60. Pyrimidine Synthesis O 2 ATP + HCO3- + Glutamine + H2O 2 ADP + Glutamate + Pi C O Carbamoyl Phosphate Synthetase II C C NH2 CH C N H PO3-2 O PRPP C O C PPi 2- O3P O Pi Reduced Quinone OMP Decarboxylase CO2 O C C CH2 C CH N H Dihydroorotase O C N H Dihydroorotate O3P O CH2 O H COO CH N O 2- CH COO Carbamoyl Aspartate CH HN CH2 HN H2O H Orotidine-5'-monophosphate (OMP) Quinone C C O OH H COO β H O NH2 COO O Dihydroorotate Dehydrogenase O HO CH2 OH Orotate Phosphoribosyl Transferase Orotate Aspartate Transcarbamoylase (ATCase) N H Carbamoyl Phosphate Aspartate C O HN O CH HN OH OH β H H H Uridine Monophosphate (UMP)
  61. 61. THANK YOU

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