Glucose Metabolism


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Glucose Metabolism

  1. 1. Cell Structure and Genetic Control
  2. 2. Cell <ul><li>Basic unit of structure and function of the body. </li></ul><ul><ul><li>Highly organized molecular factory. </li></ul></ul><ul><li>Great diversity of function. </li></ul><ul><ul><li>Organ physiology derived from complex functions of the cell. </li></ul></ul><ul><li>3 principal parts: </li></ul><ul><ul><li>Plasma membrane. </li></ul></ul><ul><ul><li>Cytoplasm and organelles. </li></ul></ul><ul><ul><li>Nucleus. </li></ul></ul>
  3. 3. Plasma Membrane <ul><li>Is selectively permeable . </li></ul><ul><li>Composition: </li></ul><ul><ul><li>Double layer of phospholipids due to hydrophobic/hydrophilic parts. </li></ul></ul><ul><ul><ul><li>Restrict passage of H 2 0 and H 2 0 soluble ions. </li></ul></ul></ul><ul><ul><li>Proteins span or partially span the membrane . </li></ul></ul><ul><ul><ul><li>Provide structural support, transport molecules, serve as receptors. </li></ul></ul></ul><ul><ul><li>Negatively charged carbohydrates attach to the outer surface. </li></ul></ul><ul><ul><ul><li>Involved with regulatory molecules. </li></ul></ul></ul>
  4. 4. Plasma Membrane (continued)
  5. 5. Cytoplasm, Organelles, Nucleoli <ul><li>Cytoplasm: </li></ul><ul><ul><li>Aqueous content of the cell. </li></ul></ul><ul><li>Organelles: </li></ul><ul><ul><li>Sub-cellular structures within the cytoplasm. </li></ul></ul><ul><li>Nucleus: </li></ul><ul><ul><li>Is a large spheroid body. </li></ul></ul><ul><ul><li>Largest of the organelles. </li></ul></ul><ul><ul><li>Contains the genetic material (DNA). </li></ul></ul><ul><ul><li>Nucleoli: </li></ul></ul><ul><ul><ul><li>Centers for production of ribosomes. </li></ul></ul></ul>
  6. 6. Cytoplasm, Organelles, Nucleoli (continued)
  7. 7. Bulk Transport <ul><li>Phagocytosis: </li></ul><ul><ul><li>Phagocytic cells use pseudopods to surround and engulf particles. </li></ul></ul><ul><ul><li>Pseudopods join, fuse, and surround ingested particle (food vacuole). </li></ul></ul><ul><ul><ul><li>Lysosomes digest food vacuole. </li></ul></ul></ul><ul><ul><li>Protects from invading organisms. </li></ul></ul><ul><ul><li>Removes debris. </li></ul></ul><ul><li>Endocytosis: </li></ul><ul><ul><li>Pinocytosis: </li></ul></ul><ul><ul><ul><li>Nonspecific process. </li></ul></ul></ul><ul><ul><ul><li>Plasma membrane invaginates, fuses, vesicle containing ECF pinches off, and vesicle enters cell. </li></ul></ul></ul>
  8. 8. Bulk Transport (continued) <ul><li>Receptor-mediated endocytosis: </li></ul><ul><ul><li>Interaction of molecules in ECF with specific membrane receptor proteins. </li></ul></ul><ul><ul><li>Membrane invaginates, fuses, pinches off and forms vesicle. </li></ul></ul><ul><ul><li>Vesicle enters cell. </li></ul></ul><ul><li>Exocytosis: </li></ul><ul><ul><li>Process by which cellular products are secreted into extracellular environment. </li></ul></ul><ul><ul><li>Proteins and other molecules to be secreted are packaged in vesicles by Golgi complex. </li></ul></ul><ul><ul><li>Vesicles fuse with plasma membrane and release contents into extracellular environment. </li></ul></ul>
  9. 9. Cilia, Flagella, Microvilli <ul><li>Cilia: </li></ul><ul><ul><li>Tiny hair-like structures that project from the surface of the cell. </li></ul></ul><ul><ul><ul><li>Stroke in unison. </li></ul></ul></ul><ul><ul><ul><ul><li>Respiratory tract, uterine tube. </li></ul></ul></ul></ul><ul><li>Flagella: </li></ul><ul><ul><li>Simple whip-like structure that propels sperm through its environment. </li></ul></ul><ul><li>Microvilli: </li></ul><ul><ul><li>Numerous folds (finger-like projections) increase surface area. </li></ul></ul><ul><ul><ul><li>Aid absorption. </li></ul></ul></ul>
  10. 10. Cytoplasm and Cytoskeleton <ul><li>Cytoplasm: </li></ul><ul><ul><li>Jelly-like matrix within the cell. </li></ul></ul><ul><ul><li>Includes organelles and cytosol. </li></ul></ul><ul><ul><li>Highly organized structure with microtubules and microfilaments that function as cytoskeleton. </li></ul></ul><ul><li>Cytoskeleton: </li></ul><ul><ul><li>Actin and myosin (microfilaments). </li></ul></ul><ul><ul><li>Spindle apparatus (microtubules). </li></ul></ul>
  11. 11. Lysosomes <ul><ul><li>Primary: </li></ul></ul><ul><ul><ul><li>Contain only digestive enzymes. </li></ul></ul></ul><ul><ul><li>Secondary: </li></ul></ul><ul><ul><ul><li>Primary lysosome fuses with food vacuole or organelle. </li></ul></ul></ul><ul><ul><ul><ul><li>Contain partially digested remnants of other organelles and organic material. </li></ul></ul></ul></ul><ul><ul><li>Residual body: </li></ul></ul><ul><ul><ul><li>Contain undigested wastes. </li></ul></ul></ul><ul><ul><li>Autophagy: </li></ul></ul><ul><ul><ul><li>Process that destroys worn-out organelles, so that they can be continuously replaced. </li></ul></ul></ul><ul><ul><li>Apoptosis (programmed cell death): </li></ul></ul><ul><ul><ul><li>Lysosomes release digestive enzymes into the cell. </li></ul></ul></ul>
  12. 12. Peroxisomes <ul><li>Membrane-enclosed organelles. </li></ul><ul><ul><li>Contain specific enzymes that promote oxidative reactions. </li></ul></ul><ul><ul><li>Oxidize molecules and form H 2 0 2 . </li></ul></ul><ul><li>Catalase: converts H 2 0 2 H 2 0 + 0 2 . </li></ul><ul><li>Oxidation of toxic molecules by peroxisomes is an important function of liver and kidney cells. </li></ul>
  13. 13. Mitochondria <ul><li>Sites for energy production of all cells; but mature RBCs. </li></ul><ul><li>Contain own DNA, can reproduce themselves. </li></ul><ul><li>Structure: </li></ul><ul><ul><li>Outer membrane: smooth. </li></ul></ul><ul><ul><li>Inner membrane: cristae. </li></ul></ul><ul><ul><li>Cristae and matrix compartmentalize mitochondrion space. </li></ul></ul><ul><ul><ul><li>Have different roles in energy generation. </li></ul></ul></ul>
  14. 14. Ribosomes <ul><li>Protein factories: </li></ul><ul><ul><li>Proteins produced according to genetic information contained in mRNA. </li></ul></ul><ul><ul><li>Located in cytoplasm and on the surface of endoplasmic reticulum. </li></ul></ul><ul><li>rRNA molecules serve as enzymes (ribozymes) required for protein synthesis. </li></ul><ul><ul><li>Contains 2 subunits composed of rRNA and proteins. </li></ul></ul>
  15. 15. Endoplasmic Reticulum (ER) <ul><li>Granular (rough) ER: </li></ul><ul><ul><li>Bears ribosomes on surface, in cells active in protein synthesis. </li></ul></ul><ul><ul><ul><li>Proteins enter cisternae are modified for secretion. </li></ul></ul></ul><ul><li>Agranular (smooth) ER: </li></ul><ul><ul><li>Provides site for enzyme reactions in steroid hormone production and inactivation. </li></ul></ul><ul><ul><li>Storage of Ca 2+ in striated muscle cells. </li></ul></ul>
  16. 16. Golgi Complex <ul><li>Stacks of hollow, flattened sacks with cisternae. </li></ul><ul><ul><li>One side of sack faces site for entry of vesicles from ER that contain cellular products. </li></ul></ul><ul><ul><li>Other site faces towards plasma membrane and releases vesicles of chemically modified products. </li></ul></ul><ul><li>Modifies proteins, separates according to destination, and packages into vesicles. </li></ul>
  17. 17. Cell Nucleus <ul><li>Most cells have single nucleus. </li></ul><ul><li>Enclosed by inner and outer membrane (nuclear envelope). </li></ul><ul><ul><li>Outer membrane is continuous with ER. </li></ul></ul><ul><li>Nuclear pore complexes fuse inner and outer membranes together. </li></ul><ul><ul><li>Selective active transport of proteins and RNA. </li></ul></ul><ul><ul><ul><li>Regulation of gene expression. </li></ul></ul></ul><ul><ul><ul><ul><li>Transport of mRNA out of nucleus to ribosomes. </li></ul></ul></ul></ul><ul><li>Nucleoli: </li></ul><ul><ul><li>DNA contains the genes that code for the production of mRNA. </li></ul></ul>
  18. 18. Chromatin <ul><li>DNA within nucleus combines with protein (histones) to form chromatin. </li></ul><ul><ul><li>Thread-like material that makes up the chromosomes. </li></ul></ul><ul><ul><li>Histone proteins are positively charged and form spools around which the negatively charged DNA strands wrap. </li></ul></ul><ul><li>Euchromatin: </li></ul><ul><ul><li>Active in genetic transcription. </li></ul></ul><ul><li>Heterochromatin: </li></ul><ul><ul><li>Contains genes that are permanently inactivated. </li></ul></ul>
  19. 19. Chromatin (continued)
  20. 20. RNA Synthesis <ul><li>One gene codes for one polypeptide chain. </li></ul><ul><ul><li>Each gene is several thousand nucleotide pairs long (DNA). </li></ul></ul><ul><li>Each gene contains the code for the production of a particular type of mRNA. </li></ul><ul><ul><li>For the genetic code to be translated into synthesis of a particular protein, the DNA code is copied onto a strand of RNA (genetic transcription). </li></ul></ul>
  21. 21. Genetic Transcription <ul><li>RNA-polymerase breaks weak hydrogen bonds between paired bases of DNA. </li></ul><ul><ul><li>Regulatory molecules act as transcription factors by binding to promoter region of gene, activating the gene. </li></ul></ul><ul><li>Double stranded DNA separates at region to be translated. </li></ul><ul><ul><li>One freed strand of DNA serves as guide. </li></ul></ul><ul><ul><ul><li>Freed bases pair with complementary RNA nucleotide bases. </li></ul></ul></ul><ul><li>RNA detaches. </li></ul>
  22. 22. Types of RNA <ul><li>4 types of RNA produced within nucleus by transcription. </li></ul><ul><ul><li>Precursor mRNA pre-mRNA): </li></ul></ul><ul><ul><ul><li>Altered in nucleus to form mRNA. </li></ul></ul></ul><ul><ul><li>Messenger RNA (mRNA): </li></ul></ul><ul><ul><ul><li>Contains the code for synthesis of specific proteins. </li></ul></ul></ul><ul><ul><li>Transfer RNA (tRNA): </li></ul></ul><ul><ul><ul><li>Decodes genetic message contained in mRNA. </li></ul></ul></ul><ul><ul><li>Ribosomal RNA (rRNA): </li></ul></ul><ul><ul><ul><li>Forms part of the ribosome structure. </li></ul></ul></ul>
  23. 23. Pre-mRNA <ul><li>Contains excess bases within the pre-mRNA. </li></ul><ul><li>Introns: </li></ul><ul><ul><li>Regions of non-coding DNA within a gene. </li></ul></ul><ul><li>Exons: </li></ul><ul><ul><li>Coding regions. </li></ul></ul><ul><li>Introns are removed and the ends of exons spliced by snRNPs to produce mRNA. </li></ul>
  24. 24. Protein Synthesis <ul><li>Each mRNA passes through ribosomes forming a polyribosome. </li></ul><ul><li>Association of mRNA with ribosomes is needed for genetic translation. </li></ul><ul><li>Translation: </li></ul><ul><ul><li>Production of specific protein according to code contained in mRNA base sequence. </li></ul></ul>
  25. 25. Protein Synthesis (continued)
  26. 26. Protein Synthesis (continued) <ul><li>Each mRNA contains hundreds of nucleotides arranged in sequence determined by the complementary base pairing with DNA. </li></ul><ul><li>Codon: </li></ul><ul><ul><li>Each 3 bases (triplet) is a code word for a specific amino acid. </li></ul></ul>
  27. 27. Protein Synthesis (continued)
  28. 28. Transfer RNA <ul><li>Translation of the codons accomplished by tRNA and enzymes. </li></ul><ul><ul><li>tRNA bends on itself, making an anticodon (3 nucleotides that are complementary to codon of mRNA). </li></ul></ul><ul><li>Synthetase enzymes join specific amino acids to the ends of tRNA within a given codon. </li></ul>
  29. 29. Formation of a Polypeptide <ul><li>Anticodons of tRNA binds to mRNA codons. </li></ul><ul><li>Each tRNA carries a specific amino acid. </li></ul><ul><ul><li>tRNA bring amino acids close together. </li></ul></ul><ul><ul><li>Amino acid detaches from tRNA. </li></ul></ul><ul><ul><ul><li>Enzymatically this amino acid is transferred to the amino acid on the next tRNA. </li></ul></ul></ul><ul><ul><li>Polypeptide chain grows. </li></ul></ul><ul><li>Interactions between amino acids cause chain to twist and fold forming secondary and tertiary structure. </li></ul>
  30. 30. Translation of mRNA
  31. 31. Functions of ER and Golgi Complex <ul><li>Proteins to be secreted by the cell are synthesized by mRNA-ribosome complexes located on granular ER. </li></ul><ul><ul><li>Proteins enter the cisternae, and are modified. </li></ul></ul><ul><ul><li>Leader sequence of amino acids is attracted to membranes of ER. </li></ul></ul><ul><ul><ul><li>Once proteins are in cisternae, the leader sequence is removed. </li></ul></ul></ul><ul><ul><ul><ul><li>Enzymatic removal of regions in protein, alter structure. </li></ul></ul></ul></ul>
  32. 32. Functions of ER and Golgi Complex (continued) <ul><ul><li>Secretory proteins are transported to Golgi complex. </li></ul></ul><ul><ul><ul><li>Further modified, packaged in vesicles, and secreted. </li></ul></ul></ul>
  33. 33. DNA Replication <ul><li>DNA is the only molecule in the body capable of replication. </li></ul><ul><li>DNA helicases break weak hydrogen bonds to produce 2 free strands of DNA. </li></ul><ul><li>Bases of each of the freed DNA strands can bind to complementary bases. </li></ul><ul><li>Each copy is composed of one new strand and one strand from the original DNA molecule. </li></ul><ul><li>Preserves the sequence of bases in DNA. </li></ul>
  34. 34. DNA Replication (continued)
  35. 35. DNA <ul><li>Law of Complementary Base Pairings: </li></ul><ul><li># of purine bases = # pyrimadine bases. </li></ul><ul><ul><li>Adenine only pairs with thymine. </li></ul></ul><ul><ul><li>Guanine only pairs with cytosine. </li></ul></ul><ul><ul><li>DNA polymerases join the nucleotides together to form a second polynucleotide chain. </li></ul></ul>
  36. 36. Cell Cycle <ul><li>Interphase (non-dividing cell phases): </li></ul><ul><ul><li>G 1 : </li></ul></ul><ul><ul><ul><li>Produces mRNA and proteins. </li></ul></ul></ul><ul><ul><li>S: </li></ul></ul><ul><ul><ul><li>If cell is going to divide, DNA replicated. </li></ul></ul></ul><ul><ul><li>G 2 : </li></ul></ul><ul><ul><ul><li>Chromosome consists of 2 chromatids joined by centromere. </li></ul></ul></ul><ul><ul><ul><li>Each chromatid contains a complete double-helix DNA molecule. Each chromatid will become a separate chromosome once mitotic division completed. </li></ul></ul></ul><ul><ul><ul><li>Completes interphase. </li></ul></ul></ul>
  37. 37. Cyclins <ul><li>Cyclins promote different phases of the cell cycle. </li></ul><ul><ul><li>During G 1 phase an increase in cyclin D proteins activates enzymes to move the cell quickly through the G 1 phase. </li></ul></ul><ul><ul><ul><li>Overactivity of a gene that codes for cyclin D might cause uncontrolled cell division (cancer). </li></ul></ul></ul><ul><li>Oncogenes: </li></ul><ul><ul><li>Mutated forms of normal genes that contribute to cancer. </li></ul></ul><ul><li>Tumor suppressor genes: </li></ul><ul><ul><li>Inhibit cancer development. </li></ul></ul><ul><ul><li>Suppressor gene p53 indirectly blocks the ability of cyclins to stimulate cell division. </li></ul></ul><ul><ul><ul><li>Induces the expression of gene p21, which inactivates the cyclin-dependent kinases. </li></ul></ul></ul><ul><ul><ul><li>Promotes cell differentiation. </li></ul></ul></ul>
  38. 38. Mitosis (M Phase) <ul><ul><li>Prophase: </li></ul></ul><ul><ul><ul><li>Chromosomes become visible distinct structures. </li></ul></ul></ul><ul><ul><li>Metaphase: </li></ul></ul><ul><ul><ul><li>Chromosomes line up single file along equator. </li></ul></ul></ul><ul><ul><ul><ul><li>Action of spindle fibers attached to kinetochore </li></ul></ul></ul></ul><ul><ul><li>Anaphase: </li></ul></ul><ul><ul><ul><li>Centromeres split apart. </li></ul></ul></ul><ul><ul><ul><ul><li>Spindle fibers shorten, pulling the 2 chromatids in each chromosome to opposite poles. </li></ul></ul></ul></ul><ul><ul><li>Telophase: </li></ul></ul><ul><ul><ul><li>Division of cytoplasm, producing 2 daughter cells. </li></ul></ul></ul>
  39. 39. Mitosis (continued)
  40. 40. Mitosis (continued)
  41. 41. Role of Centrosome <ul><li>All animal cells have centrosome, located near nucleus in non-dividing cell. </li></ul><ul><ul><li>At center are 2 centrioles. </li></ul></ul><ul><ul><ul><li>Each centriole composed of 9 bundles of microtubules. </li></ul></ul></ul><ul><ul><ul><ul><li>Microtubules grow out of pericentriolar material. </li></ul></ul></ul></ul><ul><ul><li>Centrosome replicates itself during interphase (if cell is going to divide). </li></ul></ul><ul><ul><li>Identical centrosomes move away from each other during prophase. </li></ul></ul><ul><ul><li>Take up opposite poles by metaphase. </li></ul></ul><ul><ul><ul><li>Microtubules from both centrosomes form spindle fibers. </li></ul></ul></ul><ul><ul><ul><ul><li>Spindle fibers pull chromosomes to opposite poles during anaphase. </li></ul></ul></ul></ul>
  42. 42. Telomeres and Cell Division <ul><li>Decreased ability of cells to divide is an indicator of senescence (aging). </li></ul><ul><ul><li>May be related to the loss of DNA sequences at the ends of chromosomes (regions called telomeres). </li></ul></ul><ul><ul><ul><li>Telomeres serve as caps on the ends of DNA. </li></ul></ul></ul><ul><ul><ul><ul><li>Prevent enzymes from mistaking the normal ends for broken DNA. </li></ul></ul></ul></ul><ul><ul><ul><li>DNA polymerase does not fully copy the DNA at end-regions. </li></ul></ul></ul><ul><ul><ul><ul><li>Each time a chromosome replicates it loses 50-100 base pairs in its telomeres. </li></ul></ul></ul></ul><ul><ul><li>Germinal cells can divide indefinitely due to an enzyme telomerase. </li></ul></ul><ul><ul><ul><li>Duplicates telomere DNA. </li></ul></ul></ul>
  43. 43. Meiosis (Reduction Division) <ul><li>Cell division occurring in ovaries and testes to produce gametes (ova and sperm cells). </li></ul><ul><li>Has 2 divisional sequences: </li></ul><ul><ul><li>First division: </li></ul></ul><ul><ul><ul><li>Homologous chromosomes line up side by side along equator of cell. </li></ul></ul></ul><ul><ul><ul><li>Spindle fibers pull 1 member of the homologous pair to each pole. </li></ul></ul></ul><ul><ul><ul><ul><li>Each of the daughter cells contains 23 different chromosomes, consisting of 2 chromatids. </li></ul></ul></ul></ul>
  44. 44. Meiosis (Reduction Division) (continued) <ul><ul><li>Second division: </li></ul></ul><ul><ul><ul><li>Each daughter cell divides, with duplicate chromatids going to each new daughter cell. </li></ul></ul></ul><ul><ul><ul><ul><li>Testes: produce 4 sperm cells. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Ovaries: produce one mature egg, polar bodies die. </li></ul></ul></ul></ul>
  45. 45.
  46. 46. Cell Death <ul><li>Pathologically: </li></ul><ul><ul><li>Cells deprived of blood supply swell, the membrane ruptures, and the cell bursts (necrosis). </li></ul></ul><ul><li>Apoptosis: </li></ul><ul><ul><li>Cells shrink, membranes become bubbled, nuclei condense. </li></ul></ul><ul><li>Capsases (“executioner enzymes”): </li></ul><ul><ul><li>Mitochondria membranes become permeable to proteins and other products. </li></ul></ul><ul><li>Programmed cell death: </li></ul><ul><ul><li>Physiological process responsible for remodeling of tissues during embryonic development and tissue turnover in the adult. </li></ul></ul>