UNIT I                                      Textbook of Medical Physiology, 11th Edition                                  ...
Organization of the Cell           Figure 2-1Copyright © 2006 by Elsevier, Inc.
Cell Composition                              Water    ...70-85% of cell mass                                Ions         ...
Membrane Components:                        LIPIDS:                       • barrier to water and water-soluble substances ...
Cell Membrane:       Bilayer of Phospholipids with Proteins              Figure 2-3Copyright © 2006 by Elsevier, Inc.
Proteins:       • provide “specificity” to a membrane       • defined by mode of association with the lipid bilayer       ...
Carbohydrates:       • glycolipids (approx. 10%)       • glycoproteins (majority of integral proteins)       • proteoglyca...
Carbohydrates (Cont.):       • negative charge of the carbo chains repels other         negative charges       • involved ...
Cholesterol:       • present in membranes in varying amounts       • generally decreases membrane FLUIDITY and          PE...
Cell Organelles                     Figure 2-2Copyright © 2006 by Elsevier, Inc.
The Endoplasmic Reticulum:       • Network of tubular and flat vesicular structures       • Membrane is similar to (and co...
Rough or Granular ER     • outer membrane surface     covered with ribosomes     • newly synthesized     proteins are extr...
Smooth ER      • site of lipid synthesis              - phospholipids              - cholesterol      • growing ER membran...
The Golgi Apparatus:       • Membrane       composition similar       to that of the smooth       ER and plasma       memb...
• Receives transport vesicles  from smooth ER  • Substances formed in the ER  are “processed”      - phosphorylated      -...
Exocytosis:      Secretory vesicles diffuse      through the cytosol and      fuse to the plasma      membrane       Lysos...
Secretion: • secretory vesicles containing proteins synthesized in the RER bud from the Golgi apparatus • fuse with plasma...
Lysosomes:       • vesicular organelle formed from budding Golgi       • contain hydrolytic enzymes (acid hydrolases)     ...
Lysosomal Storage Diseases           Absence of one or more hydrolases                   • not synthesized                ...
Peroxisomes:                          • similar physically to lysosomes                          • two major differences: ...
Secretory Granules                                     Figure 2-6Copyright © 2006 by Elsevier, Inc.
Mitochondria       : Primary function: extraction of energy from nutrientsCopyright © 2006 by Elsevier, Inc.              ...
The Nucleus: “Control Center” of the Cell                           The double nuclear membrane and matrix are            ...
The nuclear membrane is permeated by       thousands of nuclear pores  • 100 nm in diameter  • functional diameter    is ~...
Chromatin (condensed DNA) is found in the nucleoplasm       Nucleolus          • one or more per nucleus          • contai...
Receptor-mediated endocytosis:    • molecules attach to cell-    surface receptors    concentrated in clathrin-    coated ...
Digestion of Substances in       Pinocytotic or Phagocytic Vesicles       Figure 2-12Copyright © 2006 by Elsevier, Inc.
ATP productionStep 1.• Carbohydrates are converted  into glucose• Proteins are converted into  amino acids• Fats are conve...
The Use of ATP for Cellular Function• under “standard” conditions ∆G° is only -7.3 kcal/mole• ATP concentration is ~10x th...
The Cytoskeleton       Intermediate Filaments:             • Comprised of cell-specific fibrillar monomers             (e....
Cilia and Ciliary Movements:     • Occurs only on the inside surfaces       of the human airway and fallopian       tubes ...
Ameboid Locomotion:       • continual endocytosis at the “tail”and exocytosis at the leading edge of       the pseudopodiu...
Cell movement is influenced by     chemical substances…                                     Chemotaxis     Low concentrati...
UNIT I                                      Textbook of Medical Physiology, 11th Edition                                  ...
Central Dogma of Molecular Biology                                          DNA (genes)                                   ...
Transcription:           Figure 3-7Copyright © 2006 by Elsevier, Inc.
Overview:       Step 1. RNA polymerase binds to the promoter sequence.       Step 2. The RNA polymerase temporarily “unwin...
Messenger RNA:      • complementary in sequence to the DNA coding strand      • 100’s to 1000’s of nucleotides per strand ...
The Process of                                                            Translation           nuclear                   ...
Transfer RNA    • acts as a carrier molecule during protein synthesis    • each transfer RNA (tRNA) combines with one AA  ...
Ribosomes       Polyribosomes: multiple ribosomes can simultaneously       translate a single mRNA                        ...
Chemical Events in Protein Formation    Figure 3-11Copyright © 2006 by Elsevier, Inc.
Overview :Protein Formation       Phase 1: Initiation       • small ribosomal subunit and initiator tRNA (Met)            ...
Overview :Protein Formation       Phase 2: Elongation       • AA-tRNA binds to the ribosomal A-site       • peptidyl trans...
Overview :Protein Formation       Phase 3: Termination       • Release factor binds to the stop codon.       • Completed p...
Control of Genetic Function and Biochemical Activity                                          DNA (genes)         transcri...
Genomics                 Genomics: the large-scale study of                 the genome              • Recent estimates sug...
identify a gene                                     determine nucleic acid sequence                                       ...
Proteomics                          Proteomics: the large-scale analysis of                          proteins (i.e. the pr...
Transcriptional Control:                                 The Operon: a procaryote model • series of   genes and   their sh...
Negative Regulation       • sequences called “repressor operators” bind repressor       proteins       • binding interfere...
Positive Regulation       • so-called “activator operators” bind activator       proteins       • binding facilitates the ...
Genetic Control of Cell Reproduction    Life Cycle of the Cell:                                 M                         ...
DNA Replication: S phase       • switched on by the cytoplasmic S-phase activator       • Replication is initiated at repl...
DNA Replication: S phase       • nucleotides are always added to the 3’ end             (DNA and RNA)       • formation of...
Chromosomes and Their Replication      • “New” DNA helices associate with histones to form      chromosomes      • The two...
Stages of Cell Reproduction                                                   Mitosis: M phase                            ...
Control of Cell Growth                        What determines the rate of cell growth?                                    ...
Cell Differentiation       Different from reproduction ...       • changes in physical and functional properties of       ...
Cancer                                     Dysregulation of cell growth              Caused in all or almost all cases by ...
What causes these mutations?       • Ionizing radiation: disrupts DNA strands       • Chemicals: “carcinogens”       • Phy...
Q: Why does cancer kill?                             A: Cancer cells compete                                successfully w...
Upcoming SlideShare
Loading in …5
×

2. the cell and its function and genetic control of protein

4,670 views

Published on

0 Comments
14 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
4,670
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
778
Comments
0
Likes
14
Embeds 0
No embeds

No notes for slide

2. the cell and its function and genetic control of protein

  1. 1. UNIT I Textbook of Medical Physiology, 11th Edition Chapter 2: The Cell and its Functions Slides by John E. Hall, Ph.D. and Louise C. Nuttle, Ph.D. GUYTON & HALLCopyright © 2006 by Elsevier, Inc.
  2. 2. Organization of the Cell Figure 2-1Copyright © 2006 by Elsevier, Inc.
  3. 3. Cell Composition Water ...70-85% of cell mass Ions Proteins ...10-20% Lipids ...2-95% Carbohydrates ...1-6%Copyright © 2006 by Elsevier, Inc.
  4. 4. Membrane Components: LIPIDS: • barrier to water and water-soluble substances • organized in a bilayer of phospholipid molecules CO2 N2 O2 ions glucose H2O urea halothane hydrophilic “head” hydrophobic FA “tail”Copyright © 2006 by Elsevier, Inc.
  5. 5. Cell Membrane: Bilayer of Phospholipids with Proteins Figure 2-3Copyright © 2006 by Elsevier, Inc.
  6. 6. Proteins: • provide “specificity” to a membrane • defined by mode of association with the lipid bilayer – integral: channels, pores, carriers, enzymes, etc. – peripheral: enzymes, intracellular signal mediators K+Copyright © 2006 by Elsevier, Inc.
  7. 7. Carbohydrates: • glycolipids (approx. 10%) • glycoproteins (majority of integral proteins) • proteoglycans GLYCOCALYXCopyright © 2006 by Elsevier, Inc.
  8. 8. Carbohydrates (Cont.): • negative charge of the carbo chains repels other negative charges • involved in cell-cell attachments/interactions • play a role in immune reactions (-) (-) (-) (-) (-) GLYCOCALYX (-) (-)Copyright © 2006 by Elsevier, Inc.
  9. 9. Cholesterol: • present in membranes in varying amounts • generally decreases membrane FLUIDITY and PERMEABILITY (except in plasma membrane) • increases membrane FLEXIBILITY and STABILITY (-) (-) (-) (-) (-) (-) (-)Copyright © 2006 by Elsevier, Inc.
  10. 10. Cell Organelles Figure 2-2Copyright © 2006 by Elsevier, Inc.
  11. 11. The Endoplasmic Reticulum: • Network of tubular and flat vesicular structures • Membrane is similar to (and contiguous with) the plasma membrane • Space inside the tubules is called the endoplasmic matrix Figure 2-4Copyright © 2006 by Elsevier, Inc.
  12. 12. Rough or Granular ER • outer membrane surface covered with ribosomes • newly synthesized proteins are extruded into the ER matrix • proteins are “processed” inside the matrix - crosslinked - folded - glycosylated (N-linked) - cleaved Figure 2-13Copyright © 2006 by Elsevier, Inc.
  13. 13. Smooth ER • site of lipid synthesis - phospholipids - cholesterol • growing ER membrane buds continuously forming transport vesicles, most of which migrate to the Golgi apparatus Figure 2-13Copyright © 2006 by Elsevier, Inc.
  14. 14. The Golgi Apparatus: • Membrane composition similar to that of the smooth ER and plasma membrane • Composed of 4 or more stacked layers of flat vesicular structures Figure 2-5Copyright © 2006 by Elsevier, Inc.
  15. 15. • Receives transport vesicles from smooth ER • Substances formed in the ER are “processed” - phosphorylated - glycosylated • Substances are concentrated, sorted and packaged for secretion.Copyright © 2006 by Elsevier, Inc.
  16. 16. Exocytosis: Secretory vesicles diffuse through the cytosol and fuse to the plasma membrane Lysosomes fuse with internal endocytotic vesiclesCopyright © 2006 by Elsevier, Inc.
  17. 17. Secretion: • secretory vesicles containing proteins synthesized in the RER bud from the Golgi apparatus • fuse with plasma membrane to release contents - constitutive secretion - happens randomly - stimulated secretion - requires triggerCopyright © 2006 by Elsevier, Inc.
  18. 18. Lysosomes: • vesicular organelle formed from budding Golgi • contain hydrolytic enzymes (acid hydrolases) - phosphatases - nucleases - proteases - lipid-degrading enzymes - lysozymes digest bacteria • fuse with pinocytotic or phagocytotic vesicles to form digestive vesicles Figure 2-12Copyright © 2006 by Elsevier, Inc.
  19. 19. Lysosomal Storage Diseases Absence of one or more hydrolases • not synthesized • inactive • not properly sorted and packaged Result: Lysosomes become engorged with undigested substrate Examples: • Acid lipase A deficiency • I-cell disease (non-specific) • Tay-Sachs disease (HEX A)Copyright © 2006 by Elsevier, Inc.
  20. 20. Peroxisomes: • similar physically to lysosomes • two major differences: • formed by self-replication • they contain oxidases Function: oxidize substances (e.g. alcohol) that may be otherwise poisonousCopyright © 2006 by Elsevier, Inc.
  21. 21. Secretory Granules Figure 2-6Copyright © 2006 by Elsevier, Inc.
  22. 22. Mitochondria : Primary function: extraction of energy from nutrientsCopyright © 2006 by Elsevier, Inc. Figure 2-7
  23. 23. The Nucleus: “Control Center” of the Cell The double nuclear membrane and matrix are contiguous with the endoplasmic reticulumCopyright © 2006 by Elsevier, Inc. Figure 2-9
  24. 24. The nuclear membrane is permeated by thousands of nuclear pores • 100 nm in diameter • functional diameter is ~9 nm • (selectively) permeable to molecules of up to 44,000 MW Figure 2-9Copyright © 2006 by Elsevier, Inc.
  25. 25. Chromatin (condensed DNA) is found in the nucleoplasm Nucleolus • one or more per nucleus • contains RNA and proteins • not membrane delimited • functions to form the granular “subunits” of ribosomesCopyright © 2006 by Elsevier, Inc.
  26. 26. Receptor-mediated endocytosis: • molecules attach to cell- surface receptors concentrated in clathrin- coated pits • receptor binding induces invagination • also ATP-dependent and involves recruitment of actin and myosin Figure 2-11Copyright © 2006 by Elsevier, Inc.
  27. 27. Digestion of Substances in Pinocytotic or Phagocytic Vesicles Figure 2-12Copyright © 2006 by Elsevier, Inc.
  28. 28. ATP productionStep 1.• Carbohydrates are converted into glucose• Proteins are converted into amino acids• Fats are converted into fatty acidsStep 2.• Glucose, AA, and FA are processed into AcetylCoAStep 3. A maximum of 38 molecules of• AcetylCoA reacts with O2 to ATP are formed per molecule of produce ATP glucose degraded. (More in Chapter 67)
  29. 29. The Use of ATP for Cellular Function• under “standard” conditions ∆G° is only -7.3 kcal/mole• ATP concentration is ~10x that of ADP, the ∆G is -12 kcal/mole1. Membrane transport2. Synthesis of chemical compounds3. Mechanical work Figure 2-15
  30. 30. The Cytoskeleton Intermediate Filaments: • Comprised of cell-specific fibrillar monomers (e.g. vimentin, neurofilament proteins, keratins, nuclear lamins) Microtubules: • Heterodimers of α and β tubulin • Make up spindle fibers, core of axoneme structure Thin Filaments: • F-Actin • Make up “stress fibers” in non-muscle cells Thick Filaments: • Myosin (types I and II) • Together with actin support cellular locomotion and subcellular transportCopyright © 2006 by Elsevier, Inc.
  31. 31. Cilia and Ciliary Movements: • Occurs only on the inside surfaces of the human airway and fallopian tubes • Each cilium is comprised of 11 microtubules • 9 double tubules • 2 single tubules axoneme • Each cilium is an outgrowth of the basal body and is covered by an outcropping of the plasma membrane. • Ciliary movement is ATP-dependent (also requires Ca2+ and Mg2+) Figure 2-17Copyright © 2006 by Elsevier, Inc.
  32. 32. Ameboid Locomotion: • continual endocytosis at the “tail”and exocytosis at the leading edge of the pseudopodium • attachment of the pseudopodium is facilitated by receptor proteins carried by vesicles • forward movement results through interaction of actin and myosin (ATP-dependent)Copyright © 2006 by Elsevier, Inc. Figure 2-16
  33. 33. Cell movement is influenced by chemical substances… Chemotaxis Low concentration high concentration (negative) (positive)Copyright © 2006 by Elsevier, Inc.
  34. 34. UNIT I Textbook of Medical Physiology, 11th Edition Chapter 3: Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction Slides by John E. Hall, Ph.D. and Louise C. Nuttle, Ph.D. GUYTON & HALLCopyright © 2006 by Elsevier, Inc.
  35. 35. Central Dogma of Molecular Biology DNA (genes) RNA Proteins Structural Enzymes Cell function Figure 3-2Copyright © 2006 by Elsevier, Inc.
  36. 36. Transcription: Figure 3-7Copyright © 2006 by Elsevier, Inc.
  37. 37. Overview: Step 1. RNA polymerase binds to the promoter sequence. Step 2. The RNA polymerase temporarily “unwinds” the DNA double helix. Step 3. The polymerase “reads” the DNA strand and adds complementary RNA molecules to the DNA template. Step 4. “Activated” RNA molecules react with the growing end of the RNA strand and are added (3’ end). Step 5. Transcription ends when the RNA polymerase reaches a chain terminating sequence, releasing both the polymerase and the RNA strand.Copyright © 2006 by Elsevier, Inc.
  38. 38. Messenger RNA: • complementary in sequence to the DNA coding strand • 100’s to 1000’s of nucleotides per strand • organized in codons - triplet bases - each codon “codes” for one amino acid (AA) - each AA - except met- is coded for by multiple codons - start codon: AUG (specific for met) - stop codons: UAA, UAG, UGACopyright © 2006 by Elsevier, Inc.
  39. 39. The Process of Translation nuclear plasma envelope membrane NUCLEUS DNA (genes) DNA DNA TRANSCRIPTION RNA RNA RNA SPLICING Proteins RNA TRANSPORT Structural Enzymes TRANSLATION OF ribosomes MESSENGER RNA protein Cell function CYTOSOLCopyright © 2006 by Elsevier, Inc.
  40. 40. Transfer RNA • acts as a carrier molecule during protein synthesis • each transfer RNA (tRNA) combines with one AA • each tRNA recognizes a specific codon by way of a complementary anticodon on the tRNA molecule Figure 3-9Copyright © 2006 by Elsevier, Inc.
  41. 41. Ribosomes Polyribosomes: multiple ribosomes can simultaneously translate a single mRNA Figure 3-11Copyright © 2006 by Elsevier, Inc.
  42. 42. Chemical Events in Protein Formation Figure 3-11Copyright © 2006 by Elsevier, Inc.
  43. 43. Overview :Protein Formation Phase 1: Initiation • small ribosomal subunit and initiator tRNA (Met) complex binds to 5’end of an mRNA chain • this complex moves along mRNA molecule until it encounters a start codon (AUG) • initiation factors dissociate and large ribosomal subunit bindsCopyright © 2006 by Elsevier, Inc.
  44. 44. Overview :Protein Formation Phase 2: Elongation • AA-tRNA binds to the ribosomal A-site • peptidyl transferase joins the tRNA at the P-site to the AA linked to the tRNA at the A-site with a peptide bond • the new peptidyl-tRNA is translocated from the A-site to the P-siteCopyright © 2006 by Elsevier, Inc.
  45. 45. Overview :Protein Formation Phase 3: Termination • Release factor binds to the stop codon. • Completed polypeptide is released. • Ribosome dissociates into its 2 subunits.Copyright © 2006 by Elsevier, Inc.
  46. 46. Control of Genetic Function and Biochemical Activity DNA (genes) transcription processing transport to cytosol RNA translation mRNA stability Proteins Structural Enzymes protein activity Cell functionCopyright © 2006 by Elsevier, Inc.
  47. 47. Genomics Genomics: the large-scale study of the genome • Recent estimates suggest ~ 30,000 genes • Humans are 99.8% identical at the genome level, 99.999% identical in the coding regionsCopyright © 2006 by Elsevier, Inc.
  48. 48. identify a gene determine nucleic acid sequence (sequence homology?) Bioinformatics determine amino acid sequence (fold homology?) best guess...Copyright © 2006 by Elsevier, Inc.
  49. 49. Proteomics Proteomics: the large-scale analysis of proteins (i.e. the proteome) • “Proteome” describes the protein composition of a cell • approximately 10,000 proteins per cell, or ~15% of total possible gene products Genome ≠ ProteomeCopyright © 2006 by Elsevier, Inc.
  50. 50. Transcriptional Control: The Operon: a procaryote model • series of genes and their shared regulatory elements • gene products contribute to a common process Figure 3-12Copyright © 2006 by Elsevier, Inc.
  51. 51. Negative Regulation • sequences called “repressor operators” bind repressor proteins • binding interferes with the ability of the RNA polymerase to bind to the promoter NO TRANSCRIPTIONCopyright © 2006 by Elsevier, Inc.
  52. 52. Positive Regulation • so-called “activator operators” bind activator proteins • binding facilitates the association of the RNA polymerase with the promoter ENHANCED TRANSCRIPTIONCopyright © 2006 by Elsevier, Inc.
  53. 53. Genetic Control of Cell Reproduction Life Cycle of the Cell: M M phase: (mitosis) • mitosis G2 • cytokinesis (Gap 2) G1 (Gap 1) EUKARYOTIC Interphase (>95%): CELL CYCLE Cells that • G1 phase cease • S phase (DNA synthesis) division • G2 phase S phase(DNA synthesis)Copyright © 2006 by Elsevier, Inc.
  54. 54. DNA Replication: S phase • switched on by the cytoplasmic S-phase activator • Replication is initiated at replication origin and proceeds in both directions. • Entire genome is replicated once - further replication is blocked • involves DNA polymerase and other proteins that function to unwind and stabilize the DNA and “prime” DNA replication of the “lagging” strand.Copyright © 2006 by Elsevier, Inc.
  55. 55. DNA Replication: S phase • nucleotides are always added to the 3’ end (DNA and RNA) • formation of Okazaki fragments on lagging strand • “new” DNA is proofread by DNA polymerase • repairs are made and gaps filled by DNA ligaseCopyright © 2006 by Elsevier, Inc.
  56. 56. Chromosomes and Their Replication • “New” DNA helices associate with histones to form chromosomes • The two chromosomes remain temporarily attached at the centromere. • Together, these chromosomes are called chromatids.Copyright © 2006 by Elsevier, Inc.
  57. 57. Stages of Cell Reproduction Mitosis: M phase 1. Assembly of the mitotic apparatus 2. Prophase (A,B,C) 3. Prometaphase (D) 4. Metaphase (E) 5. Anaphase (F) 6. Telophase (G, H)Copyright © 2006 by Elsevier, Inc. Figure 3-13
  58. 58. Control of Cell Growth What determines the rate of cell growth? • growth factors • contact inhibition • cellular secretions (negative feedback) RAPID: bone marrow, skin, intestinal epithelia SLOW/NEVER: smooth muscle, neurons, striated muscleCopyright © 2006 by Elsevier, Inc.
  59. 59. Cell Differentiation Different from reproduction ... • changes in physical and functional properties of cells as they proliferate • results not from the loss of genes but from the selective repression/expression of specific genes • development occurs in large part as a result of “inductions,” one part of the body affecting anotherCopyright © 2006 by Elsevier, Inc.
  60. 60. Cancer Dysregulation of cell growth Caused in all or almost all cases by the mutation or abnormal activation of genes that encode proteins that control cell growth and/or mitosis • Proto-oncogenes: the “normal” genes • Oncogenes: the “abnormal” gene • Antioncogenes: genes whose product suppress the activation of oncogenes Not all mutations lead to cancer!Copyright © 2006 by Elsevier, Inc.
  61. 61. What causes these mutations? • Ionizing radiation: disrupts DNA strands • Chemicals: “carcinogens” • Physical irritants: e.g., abrasion of the intestinal lining • Hereditary “tendencies”: e.g., some breast cancer • Viruses: so-called “tumor viruses” (particularly retroviruses)Copyright © 2006 by Elsevier, Inc.
  62. 62. Q: Why does cancer kill? A: Cancer cells compete successfully with normal cells for limited nutrientsCopyright © 2006 by Elsevier, Inc.

×