utritional Biochemistry

1. utritionalBiochemistry İlker GÖÇHAN (M.D) Clinical Biochemistry Specialist

2. Nucleic acids, DNA and RNA structures and functions WEEK 10

3. OVERVIEW • Nucleic acids are required for the storage and expression of genetic information. • There are two chemically distinct types of nucleic acids: • Deoxyribonucleic acid (DNA) and • Ribonucleic acid (RNA)

4. Nucleotides contain; • Base + sugar + phosphoryl group

6. Purines and pyrimidines are heterocyclic compounds including N atoms

7. Nucleosides contain; • Base + sugar (ribose or deoxyribose)

9. Sugar, D-ribose or 2’-deoxy D-ribose, is linked to base via a covalent β-N-glycosidic bond to N-9 of a purine or to N-1 of a pyrimidine

10. Nucleotidesaretermedribonucleotidesordeoxyribonucleotidesbased on whetherthesugar is riboseor 2’-deoxyribose

12. DNA nucleotides

13. RNA nucleotides

14. Nucleotidesarephosphorolatednucleosides • Mononucleotidesarenucleotidessinglyphosphorolated on hydroxylgroup of thesugar • AMP → Adenosinemonophosphate • Adenine + ribose +phosphate • Additionalphosphateslinkedbyacidanhydridebondstotheexistingphosphate of a mononucleotide form nucleosidedi- andtriphosphates

15. ADP → Adenosine diphosphate • Adenine + ribose +phosphate +phosphate • ATP → Adenosine triphosphate • Adenine + ribose +phosphate +phosphate + phosphate

16. Functions of nucleotides • *Nucleic acid biosynthesis • *Energy production and transduction • *Protein biosynthesis • *Regulatory cascades • *Intra- and intercellular signal transduction • *Biosynthesis some biomolecules

17. Someproperties of nucleotides • 1.Mononucleotideshave a negativecharge at physiologicalpH • 2.Nucleotidesabsorb UV light • 3. Manycoenzymesarenucleotidederivatives • 4. Syntheticnucleotideanalogsareused in chemotherapy • 5. Nucleosidetriphosphateshavehighgroup transfer potential • 6.Somenucleotidesareinvolved in signaltransduction

18. 1.Mononucleotideshave a negativecharge at physiologicalpH. • ThepKs of theprimaryandsecondaryphosphorylgroupsareabout 1.0 and 6.2, respectively • Nucleosidesandorfreepurineorpyrimidinebasesareuncharged at physiologicalpH

19. 2.Nucleotides absorb UV light. • The conjugated double bonds of the heterocyclic bases of purines and pyrimidines ensure that nucleosides, nucleotides and polynucleotides absorb UV

20. 3. Manycoenzymesarenucleotidederivatives • AMP is present in many coenzymes

23. 4. Synthetic nucleotide analogs are used in chemotherapy • Chemically synthesized analogs of purines and pyrimidines, their nucleosides and their nucleotides find numerious applications in clinical medicine

24. Examples • 5-fluoro uracil → thymine analog • 5-iodo deoxyuridine → thyminide analog • 6-mercaptopurine → purine analaog

25. 6-thioguanine → purine analaog • 8-azaguanine → purine analaog • 5 or 6-azauridine → pirimidine analaog • 6-azacytidine → pirimidine analaog

26. 4-hydroxypyrazolopyrimidine • (allopurinol) → purine analaog • Allopurinol inhibits de novo • purine biosynthesis and • xanthine oxidase activity. • It is used for treatment of • hyperuricemia and gout

27. The nucleoside, cytarabine (arabinosyl cytosine), in which arabinose replaces ribose, is used in chemotherapy and in treatment of viral infections. • Azathioprine is catabolized to 6-mercaptopurine and is used during organ transplantation to suppress immunological rejection

28. 5. Nucleoside triphosphates have high group transfer potential because of acid anhydride bonds • High group transfer potential of nucleoside triphosphates allows them to participate as group transfer reagents in various reactions.

29. ADP and ATP are substrates and products,respectively, for oxidative phosphorylation • ATP serves as the major biologic transducer of free energy • ATP donates some of its chemical energy by hydrolysis of the terminal phosphoanhydride bond

30. 6.Somenucleotidesareinvolved in signaltransduction • cAMP and cGMP

31. cAMP (adenosine 3’,5’-monophosphate) • The cyclic phosphodiester cAMP is formed from ATP by the reaction catalyzed by adenylyl cyclase

32. cAMP is a second messenger in signal transduction • Adenylyl cyclase activity is regulated by complex interactions, many of which involve hormon receptors • As a second messenger, cAMP participates numerous regulatory functions by activating cAMP dependent protein kinases • cAMP is broken down by cAMP phosphodiesterase

33. cGMP (guanosine 3’,5’-monophosphate) • cGMP is a second messenger in signal transduction that can act antagonistically to cAMP • cGMP is formed from GMP by guanylyl cyclase • Both adenylyl and guanylyl cyclases are regulated by effectors that include hormones • A phosphodiesterase hydrolyzes cGMP to GMP

34. An increase in the level of the cGMP as response to the nitric oxide serves as the main second messenger during events that characterize the relaxation of smooth muscle

35. Nucleases • Nucleic acids are digested by nucleases • Nucleases exhibit specifity to deoxyribonucleic acids are referred to as deoxyribonucleases • Those which specifically hydrolyze ribonucleic acids are ribonucleases • Enzymes capable of cleaving internal phosphodiester bonds are referred to as endonucleases

36. Some nucleases are capable of hydrolyzing a nucleotide only when it is present at a terminal of a nucleic acid. These enzymes are referred to as exonucleases • Exonucleases can act in one direction only; 3’→5’ or 5’→3’

37. DNA

38. What is DNA ? 5:23

39. STRUCTURE OF DNA • With the exception of a fewviruses that contain single-stranded (ss) DNA, DNA exists as a doublestranded • (ds) molecule, in which the two strands wind around eachother, forming a double helix.

40. THE DISCOVERY OF DNA DOUBLE HELIX IS ONE OF THE GREATEST FINDINGS OFALL TIME, BUT IT’S ALSO ONE OF THE MOST CONTROVERSIAL.

41. KEY SCIENTISTS INVOLVED :