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Regulation of metabolic pathways

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Presentation on theme: "Regulation of metabolic pathways"— Presentation transcript:

1 Regulation of metabolic pathways

2 Bacterial control of gene expression
Operon: cluster of related genes with on/off switch Three Parts: Promoter – where RNA polymerase attaches Operator – “on/off”, controls access of RNA poly Genes – code for related enzymes in a pathway

3 Regulatory gene: produces repressor protein that binds to operator to block RNA poly

4 Repressible Operon (ON  OFF)
Inducible Operon (OFF  ON)

5 Repressible Operon Normally ON Anabolic (build organic molecules)
Organic molecule product acts as corepressor  binds to repressor to activate it Operon is turned OFF Eg. trp operon

6 trp operon

7 Inducible Operon Normally OFF Catabolic (break down food for energy)
Repressor is active  inducer binds to and inactivates repressor Operon is turned ON Eg. lac operon

8 lac operon

9 Typical human cell: only 20% of genes expressed at any given time
Different cell types (with identical genomes) turn on different genes to carry out specific functions Differences between cell types is due to differential gene expression

10 Eukaryotic gene expression regulated at different stages

11 Chromatin Structure: Tightly bound DNA less accessible for transcription DNA methylation: methyl groups added to DNA; tightly packed;  transcription Histone acetylation: acetyl groups added to histones; loosened;  transcription

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13 Transcription Initiation:
Control elements bind transcription factors Enhances gene expression

14 Transcription Initiation Complex
Enhancer regions bound to promoter region by activators

15 Regulation of mRNA: micro RNAs (miRNAs) and small interfering RNAs (siRNAs) can bind to mRNA and degrade it or block translation

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20 Embryonic Development: Zygote  Organism
Cell Division: large # identical cells through mitosis Cell Differentiation: cells become specialized in structure & function Morphogenesis: “creation of form” – organism’s shape

21 Determination: irreversible series of events that lead to cell differentiation

22 Cytoplasmic determinants: maternal substances in egg distributed unevenly in early cells of embryo

23 Induction: cells triggered to differentiate
Cell-Cell Signals: molecules produced by one cell influences neighboring cells Eg. Growth factors

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25 Pattern formation: setting up the body plan (head, tail, L/R, back, front)

26 Morphogens: substances that establish an embryo’s axes

27 Homeotic genes: master control genes that control pattern formation (eg. Hox genes)

28 Control of Cell Cycle: Proto-oncogene = stimulates cell division
Tumor-suppressor gene = inhibits cell division Mutations in these genes can lead to cancer

29 Proto-oncogene  Oncogene

30 Genes involved in cancer:
Ras gene: stimulates cell cycle (proto-oncogene) Mutations of ras occurs in 30% of cancers p53 gene: tumor-suppresor gene Functions: halt cell cycle for DNA repair, turn on DNA repair, activate apoptosis (cell death) Mutations of p53 in 50+% of cancers

31 Active oncogenes + loss of tumor-suppressor genes
Cancer results when mutations accumulate (5-7 changes in DNA) Active oncogenes + loss of tumor-suppressor genes The longer we live, the more likely that cancer might develop

32 Bacteria vs. Viruses Bacteria Virus Prokaryotic cell
Most are free-living (some parasitic) Relatively large size Antibiotics used to kill bacteria Not a living cell (genes packaged in protein shell) Intracellular parasite 1/1000 size of bacteria Vaccines used to prevent viral infection Antiviral treatment

33 Viruses Very small (<ribosomes) Components = nucleic acid + capsid
Nucleic acid: DNA or RNA (double or single-stranded) Capsid: protein shell Some viruses also have viral envelopes that surround capsid Limited host range (eg. human cold virus infects upper respiratory tract) Reproduce within host cells

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37 Simplified viral replicative cycle

38 Bacteriophage Virus that infects bacterial cells

39 Lytic Cycle of T4 Phage

40 Bacteriophage Reproduction
Lytic Cycle: Use host machinery to make copies of virus Death of host cell by rupturing it (lysis) Virulent phages replicate by this method Lysogenic Cycle: Phage DNA incorporated into host DNA and replicated along with it Phage DNA = prophage Temperate Phage: uses both methods of replication

41 Lytic Cycle vs. Lysogenic Cycle

42 Animal viruses have a membranous envelope
Host membrane forms around exiting virus Difficult for host immune system to detect virus

43 Retrovirus RNA virus that uses reverse transcriptase (RNA  DNA)
Newly made viral DNA inserted into chromosome of host Host transcribes viral DNA (= provirus) to make new virus parts Example: HIV (Human Immunodeficiency Virus)

44 HIV = Retrovirus

45 HIV Infects white blood cells HIV+: provirus (DNA inserted)
AIDS: active viral reproduction

46 Vaccines Weakened virus or part of pathogen that triggers immune system response

47 Emerging viruses = mutation of existing viruses

48 Viroids Small, circular RNA molecules that infect plants
Cause errors in regulatory systems that control plant growth Eg. coconut palms in Philippines

49 Prions Misfolded, infectious proteins that cause misfolding of normal proteins Eg. mad cow disease (BSE),Creutzfeldt-Jakob disease (humans), scrapie (sheep)

50 Diseases caused by prions
Prions act slowly – incubation period of at least 10 years before symptoms develop Prions are virtually indestructible (cannot be denatured by heating) No known cure for prion diseases

51 Tools of Genetic Engineering
Restriction enzymes (restriction endonucleases): used to cut strands of DNA at specific locations (restriction sites) Restriction Fragments: have at least 1 sticky end (single-stranded end) DNA ligase: joins DNA fragments Cloning vector: carries the DNA sequence to be cloned (eg. bacterial plasmid)


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