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Physiology of Cells
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Movements through cell membranes Basics: Movement of molecules will be either Passive or Active Passive processes require no added energy from the cell. Molecules move because of a concentration gradient. Active transport processes: REQUIRE ENERGY FROM THE CELL. Slide 2
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Examples of PASSIVE transport SIMPLE DIFFUSION OSMOSIS CHANNEL or CARRIER MEDIATED DIFFUSION FILTRATION Slid e 3
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Examples of active transport Sodium – potassium ‘pump’ Calcium pump ENDOCYTOSIS, which includes: Pinocytosis (cell drinking) Phagocytosis (cell eating) Slid e 4
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Diffusion—a passive process Molecules spread / pass through the membranes Molecules move from an area of high concentration to an area of low concentration, down a concentration gradient As molecules diffuse, a state of equilibrium will result Slide 5
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Movement of Substances through Cell Membranes Simple diffusion Solute Molecules cross through the phospholipid bilayer Certain Solutes permeate the membrane; therefore, we call the membrane ‘permeable’ to those molecules Osmosis Diffusion of water through a selectively permeable membrane, which limits the diffusion of at least some of the solute particles. Water diffuses freely. Water pressure that develops as a result of osmosis is called osmotic pressure Slid e 9
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OSMOSIS
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MOVEMENT OF SUBSTANCES THROUGH CELL MEMBRANES: PASSIVE TRANSPORT (cont.) Osmosis results in gain of volume on one side of the membrane, and loss of volume on the other side of the membrane, Whereas the osmotic pressure reaches equilibrium between the two sides.
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Osmosis Knowledge of potential osmotic pressure allows prediction of the direction of osmosis and the resulting change in pressure Isotonic: when two fluids have the SAME potential osmotic pressure HYPERTONIC (higher pressure): cells placed in solutions that are hypertonic to intracellular fluid always shrivel as water flows out of them; if pathologic conditions, or medical treatment causes the extracellular fluid to become hypertonic to the cells of the body, serious damage may occur HYPOTONIC (lower pressure): cells placed in a hypotonic solution may swell as water flows into them; water always osmoses from the hypotonic solution to the hypertonic solution
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H2OH2O.9 % Normal saline --- ISOTONIC to plasma, and to the fluid in the cells 2% or Higher saline (also D5W) (hypotonic TO THE FLUID IN the CELLS) Hypertonic to the fluid in the cells, Also to the plasma of the blood
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Facilitated diffusion CHANNEL MEDIATED OR CARRIER MEDIATED (passive Transport) A special kind of diffusion in which movement of molecules is made more efficient by the action of transporters embedded in a cell membrane (something like revolving doors) The Energy required comes from the natural collision energy of the solute ( none required from the cell ) MOVES substances down a concentration gradient ( from higher to a lower concentration)
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Channel-mediated passive transport Channels are specific; allow only one type of solute to pass through Gated channels may be open or closed (or inactive); & may be triggered by any of a variety of stimuli (ELECTRICAL, CHEMICAL, MECHANICAL) Channels allow membranes to be selectively permeable Aquaporins are water channels that permit rapid osmosis - movement of water
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Carrier-mediated passive transport Carriers attract and bind to the solute, change shape, and release the solute on the other side of the carrier. (but without expending energy) Carriers are usually reversible depending on the direction of the concentration gradient (again, it is something like a revolving door - the energy is provided by the natural tendency of the solute to go DOWN the concentration gradient. It is also something like falling into a basket and sliding DOWN a hill)
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2 special variations of passive transport: dialysis and filtration DIALYSIS : diffusion of SMALL Solute particles, but NOT Larger Molecules, Through a Selectively permeable membrane; RESULTS In Separation of the large and Small solutes. ( Movement is DOWN the concentration gradient.) ( Dialysis is used as a therapeutic process in kidney failure, to ‘artificially’ cleanse the bloodstream)
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filtration Filtration involves FORCEFUL passing of WATER and permeable SOLUTES Through a membrane, BY THE FORCE OF HYDROSTATIC PRESSURE. Hydrostatic pressure is the force, or power of A fluid pushing against a surface. (as in the Water Pressure in a pipe flowing downhill, or the water pressure generated when it is pumped through a hose or pipe.)
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Filtration The force of the Hyrostatic Pressure pushes the molecules through the sheet. (so this not dependent on a concentration gradient) A VERY IMPORTANT PROCESS IN THE KIDNEY, Which literally FILTERS the Blood, removing waste products and producing URINE. (The cardiac PUMP and systemic blood pressure provide the hydrostatic pressure)
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SUMMARY OF: MOVEMENT OF SUBSTANCES THROUGH CELL MEMBRANES: PASSIVE TRANSPORT Role of passive transport processes: Move substances down a concentration gradient, thus maintaining equilibrium and homeostatic balance Types of passive transport: simple DIFFUSION, and Facilitated Diffusion (channels and carriers); OSMOSIS is a special example of channel- mediated passive transport of water
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Movement of Substances through Cell Membranes ACTIVE TRANSPORT processes—require the expenditure of metabolic energy by the cell A. Transport by pumps Pumps are membrane transporters that move a substance against its concentration gradient—(the opposite of diffusion) Examples: SODIUM-POTASSIUM PUMP (Figure 3-19 page 92) and the calcium pump B. Transport by vesicles—allows substances to enter or leave the interior of a cell without actually moving through its plasma membrane (ENDOCYTOSIS, EXOCYTOSIS ) Slid e 23
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IN MANY WAYS Most importantly, in establishing and maintaining the TRANS- MEMBRANE POTENTIAL
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Calcium pump
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Movement of Substances through Cell Membranes Active transport processes (cont.) Endocytosis—the plasma membrane “traps” some extracellular material and brings it into the cell in a vesicle Two basic types of endocytosis (Figure 4-10): Phagocytosis—“condition of cell-eating”; large particles are engulfed by the plasma membrane and enter the cell in vesicles; vesicles fuse with lysosomes, where the particles are digested Pinocytosis—“condition of cell-drinking”; fluid and the substances dissolved in it enter the cell Slid e 26
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‘Phagocytosis’ is for engulfing and digesting unwanted invaders - but there is another type of endocytosis: RECEPTOR-MEDIATED ENDOCYTOSIS- to bring in ‘wanted’, useful molecules, (usually hormones or neurotransmitters) >>>
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: ACTIVE TRANSPORT (cont.) EXOCYTOSIS Exocytosis Process by which large molecules, notably proteins, can leave the cell even though they are too large to move out through the plasma membrane Large molecules are enclosed in membranous vesicles and then pulled to the plasma membrane by the cytoskeleton, where the contents are released Exocytosis also provides a way for new material to be added to the plasma membrane
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MOVEMENT OF SUBSTANCES THROUGH CELL MEMBRANES: SUMMARY: ACTIVE TRANSPORT Role of the active transport processes: Active transport requires energy use by the membrane, or BY THE CELL Pumps function to: concentrate substances on one side of a membrane, such as when storing an ion inside an organelle, or establishing an electrical potential across the membrane Vesicle-mediated (endocytosis, exocytosis): move large volumes of substances at once, such as in secretion of hormones and neurotransmitters
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Cellular Metabolism
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Cell Metabolism Metabolism is the set of ALL chemical reactions in a cell Catabolism—breaks large molecules into smaller ones; usually releases energy Anabolism—builds large molecules from smaller ones; usually consumes energy Slid e 33
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ENZYMES and CHEMICAL REACTIONS see chapter 2, pp.50- 54 Role of enzymes ENZYMES are PROTEINS (functional) Enzymes are chemical catalysts, They reduce the ACTIVATION ENERGY needed for a reaction, ( while they are not themselves altered or broken down by the reaction) Slid e 34
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More on Enzymes Enzymes regulate cell metabolism (orchestrate) Chemical structure of enzymes ARE IMPT. They are Proteins of a complex shape The active site is where the enzyme molecule fits the substrate molecule — (the lock-and-key model ) ENZYMES are SPECIFIC in their ACTION, and often several function together in succession
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Slid e 38 ENZYMES Most enzymatic reactions are REVERSIBLE (both ways) Metabolic PATHWAYS are regulated by a series of ENZYMES
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Collegiate ‘chemistry’ analogy: ANN and CAThy are CATALYSTS (enzymes): 1. ‘AnnABOLIC’ REACTION: ANN brings LINDA to meet BILL >>>> (add energy)... marriage, family 2. ‘CatABOLIC’ REACTION: TED/BARBARA are a couple …. TED looks longingly at CAThy walking by ; Barbara *#**@** TED with HEAT, FIREWORKS (energy released) -- Breakup/Split occurs Slid e 40
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Slid e 41 Cell Metabolism FYI Classification and naming of enzymes Enzymes usually have an -ase ending, with the first part of the word signifying the substrate or the type of reaction catalyzed specific: lipase, sucrase, etc general - TYPES of reactions/enzymes: Oxidation-reduction enzymes—known as oxidases, hydrogenases, and dehydrogenases; energy release depends on these enzymes Hydrolyzing enzymes—hydrolases; digestive enzymes belong to this group
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Slid e 42 Various chemical and physical agents known as ** allosteric effectors affect enzyme action by changing the shape of the enzyme molecule; examples of allosteric effectors include the following : Temperature Hydrogen ion (H + ) concentration (pH) Cofactors (removal, addition, changes) cofactors are nonprotein components of the enyme End products of certain metabolic pathways THIS IS PRIME EXAMPLE OF THE IMPORTANCE OF HOMEOSTASIS !!!!!! ** allosteric: ‘differing shapes’ **
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CATABOLISM CELLULAR RESPIRATION, (C/ to pulmonary respiration) the (complex) pathway in which glucose is broken down to yield its stored energy; is an important example of cell catabolism; cellular respiration has three pathways that are chemically linked : 1..Glycolysis (Taking place in cytoplasm) Glucose is broken down to 2 Pyruvate molecules, with 6 ATP produced (in the mitochondria): 2.Citric acid cycle (Figure 4-19) AEROBIC (uses oxygen) and 3.Electron transport system (ETS) (Figure 4-20) AEROBIC Slid e 45
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Slid e 46 RESPIRATION CELLULAR PULMONARY O2 into cell, breakdown of Movement of air in/out of glucose, to release energy Lungs, gas exchange ‘Internal’ respiration External resp. CHEMICAL rxns VENTILATION MICRO MACRO
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Glycolysis Pathway in which glucose is broken apart into two pyruvic acid molecules to yield a small amount of energy (which is transferred to adenosine triphosphate [ATP] and reduced nicotinamide adenine dinucleotide [NADH]) Includes many chemical steps (reactions that follow one another), each regulated by specific enzymes Is anaerobic (requires no oxygen) Occurs within cytosol (outside the mitochondria )
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CELL METABOLISM: CATABOLISM (cont.) Citric acid cycle (Krebs cycle) Pyruvic acid (from glycolysis) is converted into acetyl coenzyme A (CoA) and enters the citric acid cycle after losing carbon dioxide (CO 2 ) and transferring some energy to NADH Citric acid cycle is a repeating (cyclic) sequence of reactions that occurs inside the inner chamber of a mitochondrion; acetyl splits from CoA and is broken down to yield waste CO 2 and energy (in the form of energized electrons), which is transferred to ATP, NADH, and reduced flavin adenine dinucleotide (FADH 2 )
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CELL METABOLISM: CATABOLISM (cont.) Electron transport system (ETS) Energized electrons are carried by NADH and FADH 2 from glycolysis and the citric acid cycle to electron acceptors embedded in the cristae of the mitochondrion As electrons are shuttled along a chain of electron-accepting molecules in the cristae, their energy is used to pump accompanying protons (H + ) into the space between mitochondrial membranes Protons flow back into the inner chamber through pump molecules in the cristae, and their energy of movement is transferred to ATP Low-energy electrons coming off the ETS bind to oxygen and rejoin their protons to form water
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ANABOLISM : Protein synthesis
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Slid e 55 ANABOLISM: PROTEIN SYNTHESIS PROTEIN SYNTHESIS is a central anabolic pathway in cells {IMPORTANCE OF PROTEINS} Deoxyribonucleic acid (DNA) THE hereditary molecule the source of the information, and the director of traffic for this, and for ALL CELLULAR METABOLISM DNA : A double-helix polymer (composed of nucleotides) that functions to transfer information, encoded in genes, that directs the synthesis of proteins Gene —a segment of a DNA molecule that consists of approximately 1000 pairs of nucleotides and contains the code for synthesizing one polypeptide
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So, in Protein Synthesis, there are 3 vital Processes : TRANSCRIPTION TRANSPORT TRANSLATION
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Slid e 59 TRANSCRIPTION (of DNA) MEANS “MAKING A COPY’ (TRANS - ACROSS, SCRIPT – TO WRITE) Example: MEDICAL TRANSCRIPTION, the transcriptionist takes the spoken words and types them into a written document
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Slid e 60 TRANSCRIPTION A MOLECULE OF MESSENGER RNA IS A SINGLE STRANDED TRANSCRIPTION (COPY) OF PART OF ONE STRAND OF THE DNA MOLECULE NUCLEOTIDES IN THE NUCLEUS match up to their corresponding base, in pairs, And the mRNA is formed by action of an enzyme: RNA POLYMERASE
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CELL METABOLISM: ANABOLISM: Transcription, EDITING of mRNA, Transportation, TRANSLATION into proteins Transcription : mRNA forms along a segment of one strand of DNA Editing the transcript Noncoding introns are removed and the remaining exons are spliced together to form the final, edited version of the mRNA copy of the DNA segment Spliceosomes are ribosome-sized structures in the nucleus that splice mRNA transcripts (Box 4-4) Transportation : the mRNA is then moved out of the nucleus into the cytoplasm, to the ribosmes Translation: in the ribosomes, mRNA, tRNA and rRNA bring together amino acids in proper sequence to form the designated protein.
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Transcription, Transportation, Translation
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major Types of RNA, according to function: Messenger RNA ( mRNA) contains the message - the copy of DNA segment (gene) Transfer RNA (tRNA) transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation.polypeptide Ribosomal RNA (rRNA) is the catalytic component of the ribosomes. (brings it all together Ribosomal RNA
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Translation, resulting in Protein synthesis Translation After leaving the nucleus and being edited, mRNA associates with a ribosome in the cytoplasm tRNA molecules bring specific amino acids to the mRNA at the ribosome; type of amino acid is determined by the fit of a specific tRNA’s anticodon with mRNA’s codon As amino acids are brought into place, peptide bonds join them, eventually producing an entire polypeptide chain Translation of genes can be inhibited by RNA interference (RNAi), which protects the cell against viral infection
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tRNA, with anticodon Translation, Protein synthesis
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To summarize: key terms, processes 1. in Nucleus: TRANSCRIPTION of DNA portion (a GENE) to mRNA, EDITING, 2. TRANSPORTATION out of the nucleus, to the cytoplasm, to the 3. RIBOSOMES, ( rRNA) where TRANSLATION takes place, involving tRNA, codon (mRNA), anticodon (tRNA) Peptide bonds, Amino Acids Polypeptide = a protein
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Growth and reproduction of cells
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GROWTH AND REPRODUCTION OF CELLS Cell growth and reproduction of cells are the most fundamental of all living functions and together constitute the cell life cycle Cell growth: depends on using genetic information in DNA to make the structural and functional proteins needed for cell survival Cell reproduction: ensures that genetic information is passed from one generation to the next
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GROWTH AND REPRODUCTION OF CELLS (cont.) Cell growth: a newly formed cell produces a variety of molecules and other structures necessary for growth by using the information contained in the genes of DNA molecules; this stage is known as interphase Production of cytoplasm: more cell material is made, including growth and/or replication of organelles and plasma membrane; a largely anabolic process
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GROWTH AND REPRODUCTION OF CELLS (cont.) DNA replication (Table 4-6) Replication of the genome prepares the cell for reproduction; the mechanics are similar to RNA synthesis DNA base paring (Figure 4-29) The DNA strand uncoils and the strands come apart Along each separate strand a complementary strand forms The two new strands are called chromatids instead of chromosomes Chromatids are attached pairs, and the centromere is the name of their point of attachment
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GROWTH AND REPRODUCTION OF CELLS (cont.) Mitotic cell division: the process of organizing and distributing nuclear DNA during cell division has four distinct phases (Figure 4-31) Prophase (“before phase”) After the cell has prepared for reproduction during interphase, the nuclear envelope falls apart as the chromatids coil up to form chromosomes joined at the centromere (Figure 4-30) As chromosomes form, the centriole pairs move toward the poles of the parent cell and spindle fibers are constructed between them
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GROWTH AND REPRODUCTION OF CELLS (cont.) Mitotic cell division (cont.) Metaphase (“position-changing phase”) Chromosomes move so that one chromatid of each chromosome faces its respective pole Each chromatid attaches to a spindle fiber Anaphase (“apart phase”) The centromere of each chromosome has split to form two chromosomes, each consisting of a single DNA molecule Each chromosome is pulled toward the nearest pole to form two separate but identical pools of genetic information
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GROWTH AND REPRODUCTION OF CELLS : MIOTIC CELL DIVISION (cont.) Mitotic cell division (cont.) Telophase (“end phase”) DNA returns to its original form and location within the cell After completion of telophase, each daughter cell begins interphase to develop into a mature cell ((((((LATER)))))) Meiosis - formation of haploid gametes (to be covered) at time of reproductive system and development ch 31
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