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Cholera
• Massive diarrhoea if untreated, massive
dehydration and death.
• Catastrophic loss of body fluid (1litre/hour) = in
response to the toxin produced by the bacteria.
• The toxin -an 87-kDa protein catalyses the
formation of [cAMP].
• 100 fold increment in intracellular [cAMP] induced
by cholera toxin causes the symptoms of cholera
by inducing these epithelial cells to pour out
enormous quantities of digestive fluid.](https://image.slidesharecdn.com/cellstructurei2011compatibilitymode-230426054904-fea174dd/75/Cell-structure-I-2011-Compatibility-Mode-pdf-14-2048.jpg)
Cell structure I 2011 [Compatibility Mode].pdf
- 1. 1 Cell structure I-Prokaryotic cells Dr.S. Mukanganyama Department of Biochemistry (RM 136) University of Zimbabwe MBChB I, BDS I & NS101 2011-2012 Outline • Introduction to Biochemistry • Basic Units of life: Cells • Prokaryote ,eukaryotic cells & viruses • Role of microbial cells in disease AIDS, Cholera, Swine Flue, influenza MBCHB AND BDS 1 2011 BIOCHEMISTRY COMPONENT MARKS PRACTICALS/ASSIGNMENT/ECT 200 ORAL EXAMINATION 15 MIN 100 FINAL(PROFESSIONAL) EXAMINATION 600 TOTAL 900 PASS MARK 450 (50%) 40-49% FAIL (SUPPLEMENTARY) 39% and below FAIL (REPEAT)
- 2. 2 Biochemistry provides an understandingof: • how living things are constructed • what they contain • how they function and communicate • how they use food to obtain the building blocks and energy for growth • how genetic information is stored, expressed and passed on to the next generation • how enzymes catalyse reactions and • how the cell's chemistry is co-ordinated and controlled. • Any aspect of living tissue that can be studied in terms of chemical and physical principles is a subject for biochemical investigation. Biochemistry aims to understand the structure and function of all living things at the molecular level
- 3. 3 • Structure, organization,and functions of living matter in molecular terms. • Divided into three principal areas: 1. Structural chemistry of the components of living matter and the relationship of biological function to chemical structure. 2. Metabolism - the totality of chemical reactions that occur in living matter. 3. The chemistry of processes and substances that store and transmit biological information. Biochemistry- “the Science of life”
- 4. 4 The cell •Basic Unitsof life Variable shapes and sizes + needs energy to perform its specialised functions in maintaining life. •Smallest unit in the living organisms capable of carrying out essential life processes. Living systems: •Grow •Move •Perform metabolism •Respond to stimuli •Replicate (reproduce) with high fidelity •Life functions are ultimately interpretable in chemical terms. The Cell Theory i) Cells make up all living matter ii) Cells arise from other cells iii) Genetic information required during the maintenance of existing cells and the production of new cells passes on from one generation to the next iv) Chemical reactions of an organism i.e. metabolism takes place in cells PROKARYOTIC AND EUKARYOTIC CELLS • Prokaryotic cells "Pro"- Before nucleus. Lack a definite membrane surrounding the genetic material. In various types of bacteria. Cells invariably unicellular. • Eukaryotic cells “Eu”, - true or good and karyon for kernel or hut. Have a membrane-enclosed nucleus encapsulating their DNA.
- 5. 5 Archaebacteria Eubacteria Progenitor 3.5 billionyears ago Distinction between prokaryotic cells and eukaryotic cells artificial – share a common biochemistry Properties of Living Systems a) Biological structures serve functional purposes. to preserve the cell as a living entity. b) Actively engaged in energy transformation - ability to extract energy from the environment. • Upon death an organism at equilibrium with its inanimate environment. • steady-state-, energy and material are consumed by the organism and used to maintain its stability and order. c) Remarkable capacity for self-replication Virtually identical copies of deoxyribonucleic acid (DNA). Sexual versus asexual Simple molecules - units for building complex structures • Organisation of molecules to produce a cell/organisms • Inorganic precursors e.g. CO2, H2O, Ammonia, • Metabolites e.g. pyruvate, citrate, • Building blocks e.g. Amino acids, Nucleotides, Monosaccharides, Fatty acids, Glycerol • Macromolecules e.g. proteins, Nucleic acids, polysaccharides and lipids) • Supramolecular e.g. ribosomes, structures complexes cytoskeleton, • Organelles (Nucleus, Mitochondria, • The cell e.g. smooth muscle cell, bacterial cell • Tissues e.g. smooth muscle tissue- similar types of cells • Organs e.g. blood vessel - Different types of tissues • Sytems e.g. cardiovascular system- different organs working together closely • Organism Many organ systems
- 6. 6 Cell Structure I- Prokaryotic Cells Prokaryotes • Very small + surrounded by a rigid cell wall • Single membrane, the plasma membrane or cell membrane. • No other membranes + no nucleus or organelles. • Distinct nuclear area where a single circular chromosome is localised • Internal membranous structure, mesosome, derived from + continuous with the cell membrane for cellular respiration activities. Prokaryotes • Highly cosmopolitan + varied and highly adaptable metabolisms. • Enormous varieties of habitats. • Thrive in hostile conditions to eukaryotes e.g. in lack of O2, high temperatures + unusual chemical environments. • High reproductive rates (less than 20 min/cell division). • Resistant spores for survival of adverse conditions.
- 7. 7 Cell Wall • Rigidstructures to impart shape. • Prevents cell from expanding and bursting • Cell wall structure and synthesis is unique to prokaryotes. • Two basic types of bacterial cell wall structures Gram positive (G+) and Gram negative (G-). • Bacterial cells look very different following staining with the Gram stain. • G+ cells are Purple and G- cells are red.
- 8. 8 Structural Composition • Peptidoglycan(murein) -Polymer of N- acetylglucosamine (NAG), N-acetyl muramic acid (NAM), L-alanine, D-alanine, D-glutamate and a diaamino acid (L-lysine, L-ornithine or L- daiminobuytric acid). • (1-4) glycoside linkage between NAM and NAG. • Treatment of Gram positive (G+) bacteria with the enzyme lysozyme degrades their cell walls, which results in lysis. • Lysozyme in body secretions, including saliva, sweat, tears and vaginal secretions. • Most Gram+ bacteria contain very little lipid, but those of Mycobacterium , Corynebacterium contain mycolic acids. The Gram positive cell wall • A thick peptidoglycan layer • Very sensitive to the action of lysozyme and penicillin, or its derivatives. • Penicillin is often the antibiotic of choice for infections caused by G+ organisms. • E.g. Streptococcus pyogenes which causes strep throat. • Always treated with some type of penicillin The Gram positive cell wall
- 9. 9 Penicillin- an antibiotic •Metabolic product of one micro-organism that in very small amounts can kill or inhibit growth of other micro-organisms. • Inhibiting cell wall biosynthesis • Penicillin -1929 Sir Alexander Flemming - Penicillium notatum. • Binds to and inactivates enzymes (glycopeptide transpeptidase) that function to cross-link the peptidoglycan strands of bacterial cell walls (Reactions?) • Exposure to penicillin results in bacterial lysis. Bacterial Capsule • A viscous substance forming a layer or envelope around the cell wall of some bacteria. Functions • i) Against drying by binding water molecules • ii) Block attachment of bacteriophages • iii) Anti-phagocytic , • iv) Promote attachment of bacteria to surfaces e.g. Streptococcus mutants, (a bacterium associated with producing dental carries)
- 10. 10 1. Cell wall- Molecular composition: ------ Function: ------ 2. The cell membrane- Molecular composition: ------ Function ------- 3. Nuclear or nucleoid region- Molecular composition: ---- Function: DNA blue-print of the cell. DNA molecule replicated to yield two double -helical daughter molecules. mRNA is made (transcribed) from DNA to direct the synthesis (translation) of cellular proteins. Major features of prokaryotic cells ??? 4. Ribosomes: Molecular composition: About 15000 ribosomes. Small (30s) subunit and a larger (50S) subunit. The total size of a complete unit is 70S. Mass of 2.3 x 106 daltons. 65% RNA and 35% protein. Function: Protein synthesis. 5. Cytosol-Molecular composition: gelatinous compartment , 20% protein by weight and rich in the organic molecules that are the intermediates in metabolism. Function: Intermediary metabolism Major features of prokaryotic cells
- 11. 11 7. Flagella-Molecular composition:Threadlike appendages composed of protein. Made of a single type of protein subunit called flagellin. · Function: Locomotion + for chemotaxis. 8. Storage of genetic information Two forms DNA in bacteria: i) Chromosomal DNA ii) Plasmid DNA • Bacterial Chromosome: Single circular DNA macromolecule in nucleoid region. replication, transcription, and regulation of gene expression. • Plasmids: One or more pieces of circular macromolecules of extra-chromosomal DNA. • mating capabilities, resistance to antibiotics, tolerance to toxic metals Prokaryotic cells Polar or Monotrichous Lophotrichous Peritrichous Bacteria are capable of showing simple behavior that depends upon various stimuli. Chemotaxis - towards or away from a chemical stimulus Phototaxis - towards or away from light Aerotaxis - towards or away from oxygen Magnetotaxis - orientation in a magnetic field Cell properties from plasmid genes a. Drug Resistance- Plasmid-governed resistance mediated by enzymatic inactivation of the drug e.g. acetylation or phosphorylation b. Virulence • Genes that code for toxins e.g. the neurotoxin of Clostridium tetani, the cholera toxin of Vibrio cholerae!!!! • Genes for invasiveness. • c. Production of antimicrobial agents • E.g antibiotics; bacteriocins. d. Metabolic Activities • metabolic pathways e.g. in flavobacterium species, for nylon degradation e. Chromosome transfer • Conjugative plasmids (sex factors).
- 12. 12 Asexual reproduction Note theelectron-transparent nuclear region (n) packed with DNA fibrils, the dense distribution of ribosomal particles in the cytoplasm, and the absence of intracellular membranous organelles. Vibrio cholerae Produces the cholera toxin which causes the release of a Signalling molecule cAMP. cAMP causes the cells lining the intestines to secrete large amounts of fluids into the cavity, causing dehydration and death
- 13.
- 14. 14 Cholera • Massive diarrhoeaif untreated, massive dehydration and death. • Catastrophic loss of body fluid (1litre/hour) = in response to the toxin produced by the bacteria. • The toxin -an 87-kDa protein catalyses the formation of [cAMP]. • 100 fold increment in intracellular [cAMP] induced by cholera toxin causes the symptoms of cholera by inducing these epithelial cells to pour out enormous quantities of digestive fluid.