1 Test review: Chapter 1 Homeostasis through communication in cell (state of dynamic constancy) o Feedback loops = (+) and (-) o Ranges between a set point Hierarchy from cell to systems o Biochemical building blocks (DNA, RNA, and protein) to o Cells to o Tissues to o Organs to o Organ systems to o The human body!! Homeostasis is controlled primarily by negative feedback. o Negative feedback = sensors, set points, and integrators o Figure 1.6 = example = blood glucose Table 1.4 Set point of blood = 7.35-7.45 pH Table 1.2 only arterial blood Blood clot = positive feedback (amplifies to clot) o Small component of a negative feedback 2 systems that control most of the body function for homeostasis o Nervous and endocrine Cannon came up with the term, homeostasis Agonist acts the same as a hormone, Antagonist acts against the hormone o Antagonist of insulin is glucagon Intrinsic vs. extrinsic o Intrinsic originates from inside o Extrinsic originates from outside Exocrine vs. endocrine\ o Endocrine don't have ducts o Exocrine have ducts Know types of tissue o Most organs composed of 2 or more Know tissue information from slides only o Muscle Skeletal Striated, voluntary, individually controlled, large and multinucleated Cardiac striated, involuntary, not individually controlled, continuous as one unit Smooth Not striated, involuntary, controlled by ANS o Nervous
Neurons and supporting glial cells, conduct electrical signals, endocrine Cell body ( contains nucleus), dendrites (highly branched and receive inputs), axon (single long extension, conduct nerve impulses), glial cells (provide support - astrocytes) o Epithelial Lines and covers body surfaces, cells that form membranes and glands, tissue beneath each membrane is connective, joined by junctional complexes, separated from underlying layer by basement membrane, exocrine derived from epithelial, simple or clustered (acini) Squamous flattened o Non-keratinized living cells o Keratinized dead cells Columnar taller than wide Cuboidal cube-shaped Simple membrane one cell thick, for transport, ex) capillaries Statified membrane layers, for protection Epithelial > basement membrane > underlying tissue o Connective Lots of extracellular material, includes connective tissue proper, cartilage, blood and bone, loose connective have collagen (type of protein) and tissue fluid, regularly arranged in tendons or irregulary arranged in capsules/sheaths, adipose for fat synthesis, cartilage for support and protection made by chondrocytes and elastic material, bone with calcified material osteoblasts (bone forming), osteocytes (inactive osteoblasts), osteoclasts (bone resorbing) Blood is connective tissue Know clinical trials and processes o Phase 1 Test toxicity, metabolism, distribution in humans o Phase 2 Test on target human population (those with disease) o Phase 3 Test target population and controls in multi-center trials across large geographical area FDA approval o Phase IV Test drug for additional applications Figure 1.21!
Chapter 2 What are the big 4 organic molecules o Carbon, hydrogen, oxygen, nitrogen How electrons are involved in chemical bonding Know basic common structure
Figure 2.24 and 2.25 o Know basic parts of amino acids Amino end, R substituent, and carboxylic acid Covalent bonds o Nonpolar = stronger, equal sharing of electrons o Polar = weaker Ionic bonds o Weak bonds, but have many H bonds making it stronger Hydrophilic = water loving, hydrophobic = water hating pH vs. ion concentration o pH = -log[H+] Acid vs. Base o Acid = Proton Donor (releases H+) o Base = Proton Acceptor (releases OH) pH and buffers = how body uses carbonic acid/bicarbonate ion equation to maintain blood o Buffers one set point for blood 4 main classes of organic molecules o Carbohydrates fuel that is digested in form of amino acids to generate ATP, Lipids and proteins can also be used Glucose and glycogen Glucose into cell and used for energy Extra glucose converted to glycogen o Proteins Proteins = DNA is blue print (base, sugar, phosphate group) Code of nucleic acids Know 1' (sequence of amino acids), 2' (alpha helix or beta sheath), 3' (shaping of 2') and quaternary structure (multiple 3' combined and formed, hemoglobin) Denaturation by heat, change in pH, etc. Have 30,000 genes, but 100,000 proteins o This is because we can have modification of the proteins o Lipids steroids are most extensive, derived from cholesterol (3 six membered rings and 1 5 membered ring) Saturated = no double bonds Unsaturated = double bonds Trigylcerides = triacylglycerol Steroid hormones can diffuse hormone hydrophilic Prostaglandins as a class = structure and function Liver converts free fatty acids to ketone bodies, which can be used as an energy source, alternative to glucose o Nucleic Acids
Sugar will be ribose (RNA) or diribose (DNA) G&C, A&T (DNA) and A&U (RNA) Difference between thymine and uracil o Thymine in DNA o Uracil in RNA Hydrogen bonds facilitate in DNA and RNA G&C have 3 H-bonds A&T have 2 H-bonds No oxygen at 2' of DNA At RNA, these is a hydroxyl group o RNA molecule and get degraded tRNA = clover leaf, anticodon, amino acid attached Stereoisomers o The bonds made by carbon molecules and functional groups can have a distinct orientation in space a 3 dimensional structure Sugar will be ribose (RNA) or diribose (DNA) With synthesis, always add onto the 3' end o Biomolecules have a sense of direction Kidneys regulate the volume of blood fluid Know figure 2.10 and 2.11 L- amino acids, D- sugars are used in the body o True that body uses both stereoisomers o Mono sugar = glucose to poly sugar = glycogen o Liver and muscles store glycogen o Amino acids can be separated into nonpolar, polar, basic, and acidic Structure cytoskeleton, collagen, tendons, elastin Receptors signal transduction Carriers transport molecule across cell membrane Hormones effect on target organs and tissues Antibodies soluble immunity proteins Chapter 3 Figure 3.4 Figure 3.13 Table 3.2 Figure 3.23 *** Know all models of cell cytoplasm and nucleus..etc. Subdivisions of Cell o Plasma Membrane Selectively permeable, phospholipids bilayer Fluid mosaic model with interspersed proteins Dynamic- always changing Surrounds cell, giving it form Separates cell from outside Participates in intercellular communication
o Cytoplasm & Organelles Aqueous content inside the cell membrane but outside nucleus Organelles are subcellular inside cytoplasm Cytosol is fluid portion of cytoplasm o Nucleus Largest of organelles; within the cell Contains DNA Nucleoli- centers of production of ribosomes-site of protein synthesis Plasma Membrane Dynamics o Amoeboid Movement Involves membrane and cytoskeleton Formation of pseudopodia/membrane extensions Pseudo attach to substrate and pull the cell along Depends on bonding of membrane proteins-integrins to components of the extracellular/tissue matrix. o Phagocytosis Use pseudopods to surround/engulf particles of organic matter (bacteria) A type of cellular eating Protects the body from invading microorgs and remove extracellular debris. Ends of pseudo fuse to form vacuole. Vacuole later fuses with lysosome for digestion of contents. o Endocytosis Plasma membrane furrows inward and takes in substances No pseudopodia Two types: Pinocytosis o Membrane invaginates to produce deep furrow then fuses and a small vesicle containging the extracellular fluid is pinched off and enters the cell. o Allows cell to engulf large molecules like proteins. Receptor-Mediated Endocytosis o Smaller area of membrane, clustered receptors o Extracellular molecules bind to specific receptor proteins. o Causes to invaginate, fuse and pinch off to form vesicle. o Impt for termination of signal transduction o Exocytosis Cellular products secreted into extracellular enviro Secretory vesicles fuse with the plasma memvrane and release contents into extracellular enviro Surface area of membrane increased, replaces material lost of mem during endocytosis.
Tiny hair-like structures In humans- found on apical surface of epithelial cells in respiratory tract and female reproductive system o Flagella Long whip-like structures used for movement Only in sperm o Microvilli Membrane invaginations and folds increase membrane surface area for absorption Used for rapid passage of digested material Present in kidney tubule o Membrane Pathophysiology Aging and disease states such as inflammation create Free radicals (0H-, H2, H202) o They are chemically active o They alter proteins and destroy membrane lipids Mitochondria, inflammatory cells, and the cyclooxygenase enzyme, which synthesizes prostaglandins All generate free radicals Free radical removal decreases as cells age. If free radical production is excessive: Lipid peroxidation, loss of membrane structure and fluidity o Excessive lipid peroxidation>cell death Alzheimer's, Atheroscclerosis; inflammation Cytoplasmic Organelles o Lysosomes Membrane-bound organelles Contain proteases, phospholipases, and other enzymes to digest macromolecules Residual bodies A lysosome that that contains undigested wastes. May eliminate their wastes by exocytosis Autophagy Process that destroys worn-out organelles so they can be continuously replaced. (Eat themselves) Lysosomes are digestive system of cell. Lysosomes are important in Immune System, vision, and neurons o Peroxisomes Membrane-enclosed organelles Promote oxidative reactions, large and active in liver. Remove H from organic molecules Contain the enzyme catalase Detoxification and inactivation of organic molecs (toxins, drugs) Alcohol>acetaldehyde by liver peroxisomes Mitochondria
o Cilia
Powerhouse of the cell Contain their own DNA from orgs similar to bacteria, estab. Symbiotic relationship with primitive euk cells Replicate independently of mitosis Inheritance is maternal o Mitochondrial Pathophysiology Leber's Heredity Optic Neuropathy Leads to blindess Passed from mom to kid Defect in Mitochondrial DNA Ribosomes o Protein Factory, from mRNA o Free in Cytoplasm and on ER Endoplasmic Reticulum o Long, branched tubular structure o Contiguous with nuclear membrane Smooth ER Steroid Synthesis Calcium Storage Signal Transduction Deactivation of Drugs Rough ER Contain Ribosomes Site of secretory and membrane protein synthesis o Pathophysiology of ER When taking drugs for long period of time Large doses required to achieve effect produced initially A need of a higher dose o Tolerance of Enzyme Induction Phenobarbital is oxidized (inactivated( by enzymes of Smooth ER in liver Constant exposure of liver cells to Phenobarbital increases production of enzymes that inactivate the drug (Induction) Causes a tolerance-more drug is needed to produce same effect. Alcohol causes tolerance Liver cells of substance abusers have increased amount of smooth ER Golgi o Series of flattened sacs (cristernea) o Proteins synth in Rough ER then moved to Golgi o Proteins pass from ER nu vesicle and fuse with 1 side of the Gogli o Proteins processed and sorted for membrane/organelle delivery Cytoskeleton o Network of structural proteins that interconnects plasma mem and organelles
Movement of organelles Secretion Translocation of enzymes o Tensegrity As cells mature in an organ they develop distinct cytoarchitecture, impt to cell function Nucleus o Bounded by nuclear membrane with nuclear pores Contains DNA and chromatin Site of mRNA transcription Transported to cytosol and translated Life and Death of a Protein o Transcription (RNA synthesis) In order for genetic code to be translated into specific proteins DNA code first copied onto a strand of RNA Only 1 of the 2 strands in DNA is used to from single-stranded molecule of RNA o Pre-mRNA In nucleus and froms mRNA o mRNA messenger and contains the code for synthesis of specific proteins o tRNA transfer is needed for decoding the genetic message contained in mRNA. o rRNA ribosomal, forms part of the structure of ribosomes o Translation Association of mRNA with ribosomes needed for this Production of specific proteins according to the code contained in the mRNA base sequence Codon o Every 3 bases have a code word for a specific amino acid o As mRNA moves through ribosome, the sequence of codons translates into a sequence of specific amino acids within a growing polypeptide chain. Anticodon o tRNA forms a cloverlead structure and one end contains anticodon o three nucleotides that are complementary to a specific codon in mRNA. Anticodons of tRNA bind to codons of mRNA. After Translation: o Translated proteins are directed to specific sites o Signal sequence is a specific group of amino acids, usually at one end of the protein
o Proteins destined for secretion contain a sequence that directs movement through the golgi. In Golgi: o Proteins are sequestered into vesicles for destination o Additional signal sequences direct proteins to plasma mem, mitochondria, etc o Signal sequences also direct port-translational modifications. Chapter 4 Figure 4.11 Enzymes All chemical possible rxns in nature Absence of added E rate of rxns is slow Cells use enzymes to speed up chem. Rxns o Catalysts Increase rate of rxns Remain unchanged Don't change nature of rxn or final result o Enzymes are generally proteins, except ribozymes o Act by decreasing activation energy required for chem. Rxn o Molecule or reactant the enzyme changes is Substrate Decrease activation energy by: o Bringing reactants into close proximity, at the active site o Formation of an enzyme-substrate complex that has more energy than the individual reactants. Enzyme Models Lock and Key- substrate & active site fit together Induced Fit-cofactor causes change in conformation of active site, changes to fit the substrate Dignostic Use of Plasma Enzymes Isoforms- same enzyme, tissue specific, amino acid sequence Creatine Phosphokinase (CPK, CK) Isoforms o MM-Skeletal Muscle o BB-Brain o MB-Heart Tissue-specific isoforms are released by damaged tissue Measurement of isoforms using monoclonal antibodies aids in diagnosis of disease. Physiological Enzyme Activity is Tightly Controlled o Temperature Most enzymes have a temp at 37 o C At 0 o C enzymes have immeasurable activity Temps higher than 40, most enzymes inactive o pH optima spans the pH scale
Pepsin =2 Trypsin=8 pH optima of purified enzymes in a tests tube is not relevant pH o Cofactors Include metal Ions: (Ca2+, Mg2+, Zn2+. Mn2+, Cu2+) Induce shape change in active site of enzyme to enhance formation of the ES complex o Coenzymes Organic molecules. Not necessarily enzyme Derived from water soluble vitams (niacin, riboflavin, pyridoxine) Transport small molecules such as H atoms to active site of enzymes. o Zymogens Enzymes produced in inactive form Proteolytic Cleavage converts enzyme to active form Pancreatic enzymes-insulin o Phosphorylation Add phosphate group Added by enzymes called protein kinases Adding phosphate group can activate enzyme Deactivate enzyme Increase/decrease activity Phosphate groups removed by phosphotases o Substrate Concentration Enzyme activity increases as substrate conc increases, to a plateau At plateau, all available enzymes are at maximum velocity Any further increase produces no change in rxn rate At this point enzyme is saturated o Reversible Reactions Some enzyme catalyze forward and reverse reactions Carbonic anhydrase (Look on notes for formula) Law of Mass Action o Rxn driven from side of equation where product conc is higher to side where is it lower Metabolic Pathways o A sequence of enzymatic rxns that begins with an initial substrate, progresses through a number of intermediates and ends with a final product. o Enzymes linked in sequences of rxns that form metabolic pathways Examples Glycolysis Lactic Acid Glycogenesis Glycogenolysis Cori Cycle Krebs Cycle
ETS Substrate Inhibition o AKA end product inhibition Negative feedback inhibition The conc of final product in a metabolic pathway inhibits an enzyme earlier in the sequence. Prevent over accumulation of final product Can shift pathway to production of another intermediate Allosteric Inhibition o Mechanism by which an endproduct inhibits an enzyme o End product/allosteric inhibitor binds toa site on the enzyme that's not the active site. o Binding induces shape change in the enzyme which inhibits its activity o Directed by concentration of the allosteric inhibitor. (see pic on slides) Inborn Errors of Metabolism: o Each enzyme in metabolic pathway is controlled by a separate gene. o An inherited defect in gene may result in inborn error of metabolism o Intermediates upstream of the defect accumulate o Downstream of the defect decrease o Results in a disease state Bioenergetics o The flow of energy in living systems Free Energy o Energy that exists in an organized state can be used to do work Law of Thermodynamics o Law of conservation of energy- E can be transformed, cannot be created/destroyed o Universe is increasing in entropy o The higher the entropy the lower the free energy o Systems tend to go from a state of high free energy to low free energy o Body is highly ordered low entropy o Body should increase in entropy/more disordered with time o To maintain high order, low entropy- body must constantly utilize free energy Endergonic Reactions o Input of E o Products contain more E than reactants o Products lower entropy o Synthesis of proteins o Contraction of muscle Exergonic o Releases free energy o Products less free E o Higher entropy o Released E can be harnessed to do work o Gylcolysis
Coupled Reactions o In order for body to perform endergonic Rxn, must consume free E from exergonic Rxns o Endergonic coupled with exergonic by cells of the body. Measurement of E o Obtains E to do work from enzymatic oxidation of food o E in food is measured by amt of E released during combustion o Calorie The amt of heat required to raise temp of one cubic centimeter of water one degree Celsius. Physiological Energy Currency o Body cannot use heat as energy source o E released by exergonic oxidation of food is converted to chem. Energy o Universal carrier in cells of body is (ATP) NAD and FAD o Not E carriers o Trasnport H+ for oxidative phosphorylation generates ATP o Niacin and Riboflavin synthesize NAD and FAD Chapter 5 Aerobic respiration = 02 is final electron acceptor Know figures ATP is the goal o Glycolysis = 2 net ATP, 2NADH o Oxidative phophorylation = 26 total o Kreb's cycle (run twice = X2) = (1 Reduced FAD (FADH2), 3 reduced NAD (NADH), 1 ATP) X 2 = 2 FADH2, 6 NADH, 2 ATP Oxaloacetic acid works with Acetyl CoA to form citric acid o Transfer involves oxidation-reduction reactions Lactic Acid Pathway o Anaerobic, happens when O2 is lacking, pyruvate reduced, lactic acid formed Figure 5.10, know H ions are being pumped out by 2nd and 3rd pump across intermembrane = get used by ATP synthase (protein) = high concentration gradient push it down pump so then ATP is made. Chemiosmotic Theory = ETS & OP o Pumps and ATP synthase (enzymes used in process) used to oxidize Know metabolic processes to produce ATP Coenzymes = small organic molecules o NAD, FAD, acetyl CoA Forms 2 pyruvic acids through glycolysis Anaerobic final electron acceptor is pyruvic acid o Converted to lactic acid Ischemia = tissue doesn't receive adequate blood and tissue dies (no oxygen) o Heart attack
Angina = take pills and muscles will get bigger so more blood flow Infarct = cells die Glyconeogenesis = new glycogen process Figure 5.4 o Don't need to know the intermediates except glucose 6 phosphate o Glucose through tissues to glucose 6 phosphate through liver to glucose o Glycogenolysis produces glucose-6-phosphate o In liver, G-6-P can be converted to glucose and released to the blood, via the enzyme glucose -6- phosphatase o Glycogenesis And Glycogenolysis Cori cycle o Lactic acid, amino acids, and glycerol can also be converted to G-6-P and glucose by the liver LDH = lactate dehydrogenase enzyme used during exercise because oxygen is used up In metabolism = understand lipids and proteins broken down for alternative source of energy o Know processes of energy conversion Beta oxidation - fatty acid/triglyceride (triaclyglycerol) Glycolysis - glucose Hydrolyze - glycogen Trans-amination (moving amine group from one amino acid to another), oxidative deamination (removes amine groups from amino acids) - amino acids/proteins Essential vs. nonessential Get some in diet, conversion of amino acids Proteins get recycled Figure 5.16 = see how proteins fit in Figure 5.17 o Pyruvic Acid to Acetyl CoA is nonreversible Metabolism has to do with energy transfers o Catabolic = break down of glucose, fatty acids, and proteins for energy use o Anabolic = Building up; reactions are fueled by ATP and synthesize new cellular macromolecules ATP made directly and via oxidative phosphorylation Table 5.1 Glycogenesis, glycogenolysis and gluconeogenesis Acetyl CoA pyruvic acid + coenzyme A = Acetyl coenzyme A (done through reduced NAD to NADH) Free radicals and antioxidants. Know clinical box on page 112 Cyanide it blocks the transfer of electrons from cytochrome a3 to oxygen. Metabolism of lipids and proteins Lipogenesis and lipolysis -Oxidation, trans-amination and oxidative deamination
Ketosis the secretion of abnormally high amounts of ketone bodies into the blood, a sign of fasting or an uncontrolled diabetic state Interconversion of glycogen, fat and protein Figure 5.17 Chapter 6 Diffusion through Plasma Membrane Bulk transport-more than one molecule across membrane (steroids) o Movement of water and solutes is critical to physiological function provide nutrients to cells transport hormones and signaling molecules circulation function of kidneys function of nervous system Properties of Plasma Membrane o Hydrophobic molecules readily penetrate the membrane o Small inorganic ions can pass through channels in the membrane Categories of Transport o Passive Net movement of ions down a concentration gradient (high to low) No ATP Types Simple diffusion Osmosis Facilitated Diffusion o Active Against concentration gradient (low to high) Requires ATP Requires specific transport proteins Types Primary Secondary Diffusion o Movement of a molecule/ion from high to low concentration o Example-gas exchange o Glucose is small but cant diffuse across membrane, needs facilitated diffusion (help) Osmosis o When a membrane is not permeable to a solute o Net diffusion of water o Simple diffusion of solvent instead of solute In the cell Water enters and leaves cell Can move through lipid bilayer Aquaporins
Osmotic Pressure o Osmosis of water can be blocked by pushing against the membrane with a certain amount of force o Force that would have to be exerted to prevent osmosis is osmotic pressure which is a property of solute molecules Pure water has osmotic pressure of 0 Is a property of the higher solute solution Fluid Compartments o Intracellular fluids Cytosol o Extracellular fluids Plasma Interstitial fluid Fluid that lies between the cells in tissue Space between the cells-interstitial space Pathophysiology of Osmosis o Water moves from tissue to plasma bc protein in it is higher o Plasma proteins cant enter interstitial fluid o Osmotically active-solute that cannot cross a membrane barrier Promotes osmosis o Abnormally low plasma proteins= excessive tissue fluid edema Measurement of Osmotic Properties o Molarity I M of solute dissolved in water to make 1L of solution is described as 1 M solution M/L o Molality In 1 M solution 1 mole of solute is dissolved in 1 kg of water. M/Kg Osmolality o Total molality of a solution based on sum of all solutes In the presence of ions: Molecules like NaCl ionize in water I mole of NaCl yields o I mole of Na+ o I mole of CLA 1 m solution of NaCl is 1 m Na+ plus 1 m Cl- = 2 Osm Osmolality of Physiological Fluids o The fluids are complex o Cant estimate osmolality thru calculation Intravenous Fluids o Since 5% dextrose and normal saline have the same osmolality as plasma, they are isotonic to plasma. Solutions with the same (osmotically active solutes) as plasma are isotonic Solutions with higher ( ) than plasma are hypertonic (crenation) Solutions with lower ( ) than plasma are hypotonic (swelling)
Tonicity o Desrives the effect of osmotically active solutes on the osmotic movement of water. Facilitated Diffusion o AKA carrier-mediated transport o Passive- no E required o Transports ion down its conc gradient from high to low concentration o Requires carrier protein o Characteristics similar to enzymes Specificity Competition Saturation o GLUT Glucose transport carrier proteins GLUT4- skeletal muscle isoform Stored in cytoplasmic vesicles Inserted in membrane in response to insulin stimulation or exercise. Pathophysiology of Facilitated Diffusion (Picture in notes) Active Transport o Requires transporter protein o Calcium- 100nm intracellular vs 1 mm extracellular o Requires input of E o Types Primary Active Transport Hydrolysis of ATP is directly coupled to action of transporter Trasnporter integral membrane protein o Molecules to be transported binds to recognition site on one side of carrier protein o ATP used to phosphorylate it o Causes change in transporter protein o Molecule released on opposite side of membrane using a hinge-like motion o The Sodium- Potassium Pump Primary active transport carriers--pumps Transport 1 molec at time Exchange molec for others Na+ is higher extracellularly K+ higher intracellularly (see slides) Secondary Active Transport Coupled Transport E required for movement of a molecule against conc gradient is obtained from the Na+ gradient ATP hydrolysis is required indirectly
Diffusion of Na+ down its concentration gradient powers the movement of another ion, against its concentration grandient. Types o Cotransport or symport The molecule to be transported is moved in same direction as Na+ (in cell) o Antiport or countertransport A momlecule is transported in the opposite direction of Na+ (out of cell) (see slides) Intracellular Low Na+, Low Ca2+ Extracellular High Na+, High Ca2+