1. 1 The flow of biological information DNA RNA Protein Cell Structure and Function Noncovalent Bonds Storage of Biological Information in DNA Transfer of Biological Information to RNA Protein Synthesis Errors in DNA Processing Signal Transduction through Cell Membranes Diseases of Cellular Communication Noncovalent Bonds Storage of Biological Information in DNA Transfer of Biological Information to RNA Protein Synthesis Errors in DNA Processing Signal Transduction through Cell Membranes Diseases of Cellular Communication

2. 2 Biochemistry and communication Much study on how cells and organisms communicate - hormones, pheromones, neurotransmitters. DNA, RNA, proteins and other large molecules contain much information that is need for cellular processes. DNA DNA - information storage RNA RNA - information retrieval Protein Protein - information processing

3. 3 Communication between cells Multicellular organisms need a way to coordinate activities between cells. Most cells produce and secrete molecules to pass information to others - cause an effect on a target cell site. signal transductionThe most common mechanism for transmembrane communication is signal transduction. Regulation of glucose is a good example.

4. 4 Communication between organisms. One or more chemicals are released to the environment by an organism. Other organisms can detect these chemicals at very low levels. Pheromones are a well known examples. CH 3 O | || CH 3 CHCH 2 CH 2 OCCH 3 CH 3 CH 2 CH=CH(CH 2 ) 9 CH 2 OCCH 3 isoamyl acetate (honey bee alarm) tetradecenyl acetate (european corn borer sex pheromone) O ||

5. 5 Biological and noncovalent interactions DNA, RNA, proteins and some carbohydrates are informational molecules. Information is retrieved by ‘reading’ the sequence of monomeric units in them (molecular recognition). Noncovalent forces are used to read this information - van der Waal’s, ionic, hydrogen and hydrophobic interactions.

6. 6 Common properties of noncovalent bonds Three common characteristics. Forces are relatively weak and noncovalent. 1-30 kJ/mol, compared to the 350 kJ/mol for a C-C single bond. Single interactions are typically not sufficient to hold two species together. Several such interactions can participate at the same time.

7. 7 Common properties of noncovalent bonds The bonding process is reversible. Molecules diffuse and will come close enough for contact. Thermal motion assists in making the proper contact. It does not last more than a few seconds. Additional thermal motion will cause the intermediate form to ‘fall apart.’

8. 8 Common properties of noncovalent bonds Binding is specific Due to the size and shapes of the molecules, only certain species are able to align properly. Complementary noncovalent interactions are also required. Size, shape and type of interaction all must be correct for binding.

9. 9 Storage of biological information genome Total genetic content in a cell is called the genome. This information is stored in a long, coiled DNA molecule. It is used two ways. Duplication during cell division Manufacture of RNA

10. 10 DNA molecule hetropolymer Consists of a long, unbranched hetropolymer - more than one type of monomer unit. deoxyribose phosphate nitrogen base (4 types) O | O -- P -- O -- || O - CH 2 O OH O | O -- P -- O -- || O - CH 2 O O | O -- P -- O -- || O - CH 2 O O - | O -- P -- O -- || O - CH 2 O N C C C C N N N CH NH 2 | H N C C C C N O NH 2 | H H N C C C C N N N CH O || H H2NH2N N C C C C N O H H O || CH 3

11. 11 DNA molecule N C C C C N N NHNH CH NH 2 | H N C C C C N N NHNH CH O || H H2NH2N adenine guanine N C C C C N H O NH 2 | H H N C C C C N H O H H O || CH 3 cytosine thymine

12. 12 DNA molecule

13. 13 DNA molecule Strands form complementary base pairs. The entire human genome takes 1 meter of DNA - 3 billion base pairs. G T C A C G A C T G

14. 14 DNA replication This is a self-directed process that relies on many “accessory” proteins. Each strand serves as a template during replication by unwinding in small regions. DNA polymerase is used to covalently link the DNA backbone. semiconservative This is semiconservative since each new DNA molecule contains one new and one original strand.

15. 15 DNA replication

16. 16 Why DNA? DNA is a very stable molecule Survives under extracellular conditions. Covalent backbone is chemically stable in aqueous environments. Sixty five million year old dinosaur samples and 120 million year old weevil samples have been found to still contain large amounts of DNA.

17. 17 Transfer of biological information Transcription Production of RNA from DNA. Only a small portion of a DNA strand is actually used during a transcription. Much of DNA’s information is used to make RNA but not all of it. Some traits are not expressed. Some regions in prokaryotic cells are not usable.

18. 18 Transcription Production of RNA is similar to DNA replication. The differences are: Ribonucleotides are used. Uracil replaces thymine. RNA:DNA hybrid duplex product eventually unravels and RNA is released. RNA polymerase is used to link nucleotides. The product is a single-strand species.

19. 19 Types of RNA There are three types of RNA. All share some common properties. All are single strands. All are produced by DNA transcription using RNA polymerase (except RNA viruses). All play roles in protein synthesis.

20. 20 Ribosomal RNA (rRNA) The most abundant type of RNA. A combination of protein and rRNA molecules is used to form ribosomes. These are the sites of protein synthesis. Multiple RNA strands are used in each ribosome.

21. 21 Transfer RNA (tRNA) The smallest type of RNA molecule, consisting of 73-93 nucleotides. They combine with amino acids and act to transport them to the site of protein synthesis. At least one type of tRNA for each amino acid.

22. 22 Transfer RNA (tRNA)

23. 23 Messenger RNA (mRNA) The information from a single gene. The ‘tape’ that is read by the ribosome when producing a protein. It is unstable and rapidly decays. mRNA ribosome 5’ end 3’ end growing peptide complete peptide

24. 24 Protein synthesis mRNA is the intermediate carrier of DNA information. It is a linear sequence of bases used to make a sequence of amino acids - protein. translation The process is called translation. tRNA rRNA DNAmRNAprotein

25. 25 The genetic code The order of bases in DNA will specify which amino acids are used in a protein. Triplet code - three bases are needed to specify an amino acid. The sets of three bases are nonoverlapping and read sequentially. An amino acid may have more than one code (degenerate), but no amino acids share the same code. Stop and start codes are also used. Code is nearly universal for all life.

26. 26 Exons and Introns In prokaryotic cells, DNA is read from “start” to “stop”, producing mRNA. For eukaryotic cells, sections of mRNA are removed prior to producing protein. It appears that DNA contains noncoding regions. exons exonscoding regions of DNA introns intronsnoncoding regions of DNA

27. 27 Exons and Introns Exons Contain 120-150 bases used to represent a 40 - 50 amino acid sequence.Introns 50 - 20,000 bases. Purpose is unknown; may be evolutionary “junk DNA.” Absent in prokaryotes, rare in lower eukaryotic cells like yeast.

28. 28 Exons and Introns Newly synthesized mRNA is longer than the final, mature form. Final form is the result of extensive post- processing to remove regions produced from intron regions. Maturing of mRNA may require several accessory enzymes. It’s not uncommon for a gene to contain two or more introns.

29. 29 Errors in DNA processing DNA mutations Millions of years of evolution have resulted in replication, transcription and translation processes that are highly accurate. mutations Errors can still occur - mutations - at a rate of about 1 error/10 9 nucleotides. Mechanisms to repair mutations have also evolved.

30. 30 Errors in DNA processing The effect of mutation is based on the area where it occurs. For intron region, it has no real effect. If it occurs in an exon region, it may alter the amino acid sequence of a protein. One example - sickle cell anemia Only two “incorrect” amino acids out of 546 in hemoglobin. Results in a very significant change.

31. 31 Errors in DNA processing NormalSickle Hemoglobin

32. 32 Signal transduction through cell membranes Information transfer by signal transduction. Many biological activities require precise coordination - both in and between cells. The more highly developed the organism, the greater the need for coordination. Different organs take on specific roles. Chemicals like hormones and growth factors are used by one cell to alter the activities of another. Target cells use receptors on their surface to recognize signal molecules.

33. 33 Signal transduction through cell membranes Examples of ‘signal’ molecules Prostaglandins Control many functions like contraction of smooth muscles and blood platelet aggregation. Insulin and Glucagon Glucose regulation. Sex hormones Secondary sex characteristics.

34. 34 Signal transduction through cell membranes The process used for transduction will vary for each hormone. Each will follow a general series of events. At least three types of protein are used. Binding site protein G protein Adenylate cyclase

35. 35 Steps in signal transduction Hormone is picked up by the target cell because it contains a receptor site to accept it (binding protein)

36. 36 Steps in signal transduction Binding stimulates the receptor site to interact with a G protein in the inner membrane. “G” because the protein will bind guanine nucleotides (GDP, GTP).

37. 37 Steps in signal transduction Activated G protein passes signal to an enzyme (typically adenylate cyclase) which either stimulates or inhibits it.

38. 38 Steps in signal transduction Adenylate cyclase catalyzes the formation of cyclic adenosine 3’,5’- monophosphate (cAMP) from ATP.

39. 39 Steps in signal transduction cAMP then goes on to do whatever it is required to do. It acts as a secondary, short- lived messenger.

40. 40 Control of glucose levels Insulin Hormone produced by the beta cells in the pancreas. Stored as proinsulin (inactive form) as small granules. Release is triggered by increased glucose levels in the blood. Stimulates glucose uptake by tissue by binding to receptors in the cell membrane. Permits glucose to enter cell.

41. 41 Control of glucose levels High glucose level Production of insulin in pancreas Insulin binds to site on cell membrane which allows glucose to enter Glucose can then be used by the cell or stored as glycogen (liver or skeletal muscles).

42. 42 Control of glucose levels Glucagon This hormone is also produced in the pancreas in an inactive form. Low glucose levels result in its conversion to an active form and its release. Its entry into liver cells results in the conversion of glycogen to glucose, with glucose being released to the blood.

43. 43 Control of glucose levels Low glucose level Production of glucagon in pancreas glucagon Targets site on liver cell membrane (adenylate cyclase) Glucagon starts process that converts glycogen to glucose glucose enters blood

44. 44 Control of glucose levels Epinephrine Adrenaline - ‘flight or fight hormone’ Similar in effect to glucagon but affects primarily muscle tissue. It also affects the nervous system. Results in a very rapid “all systems ready.”

45. 45 Control of glucose levels Approach of large carnivorous animal! Production of epinephrine by adrenal gland epinephrine Targets site on muscle cell membrane epinephrine starts process that converts glycogen to glucose glucose enters blood

46. 46 Characteristics of signal transduction Chemical signal that results from hormone binding is amplified. Many molecules of cAMP can be produced from a single hormone signal Hormones are usually released by the endocrine system on demand. Not continuous - system can make changes as needed. Rapid release and transient existence provide for ability to respond quickly.

47. 47 Diseases of cellular communication Example - Cholera toxin Interferes with the normal action level of G protein. Causes continuous activation of adenylate cyclase. Results in high cAMP levels in epithelial cells of the intestine. Causes uncontrolled release of water and sodium, leading to diarrhea and dehydration.

48. 48 Diseases of cellular communication Work is being conducted to develop new drugs - three approaches Function at DNA level Block transcription of disease genes. Interfere with translation of mRNA. Bind to receptor proteins Block toxins, viruses... Interfere with signaling pathways in cell Small, nonpolar chemicals that inhibit proteins involved in signaling process.