Introduction to the Biology of Mammalian Organisms

1. Introduction to the Biology of Mammalian Organisms Stan Misler Fall 2016 Human Anatomy and Physiology latrotox@gmail.com

2. Why study human anatomy and physiology?

3. Why study human anatomy and physiology? • Satisfy intellectual curiosity about organization and operation of one of most complex living organism consisting a host of interacting organ systems • Understand how humans respond to physiological stress (ex. shock, exercise, development) • Understand the bases for major chronic disease processes (Coronary artery disease, hypertension, stroke, diabetes, obesity, asthma, cystic fibrosis, celiac disease, osteoporosis, cirrhosis, substance addiction and dementia) and how they may be prevented or have their progression slowed

4. 1. "What is Life?" Cell-based multi-tasking chemical reactor functioning by way of nano-devices* (proteins or nucleic acids) that are in the cytoplasm (cell sap = watery gel), in intracellular organelles and in the surrounding cell membrane (a lipid bilayer). In commercial bulk chemical reactorslarge quantities of reactants are mixed and desired product is later purified; in cell-based nanodevices reactions are accomplished via tiny (nanometer) changes in the folding of proteins occurring over microseconds. In both types of reactors the processes undertaken obey fundamental laws physics and chemistry (generation of heat or increase of disorder or entropy), However, uniquely the cell (a) stores energy in chemical bonds (ATP = ADP~P); (b) is self perpetuating (renewal of protoplasm and transmission of genetic program to progeny); (c) is self regulating (through feedback to maintain constant levels of some function); and (d) is self adapting to environment. *Prototypic biological nanodevices work via stepwise changes in shape enzyme = a protein catalyzing the alteration of chemical bonds ion channel = protein with pore down middle that selectively allow transport of some species of ions (Na, K, Ca, Cl) molecular motors twisting their “heads” cell surface receptors operating a switches: bind ligands, change shape and set off intracellular chemical cascade (transduction)

5. - Conformational changes in single protein molecules as basis forall cellular functions Nanodevices now and for the future - Ability to watch individual molecules “in the act” (e.g., ion channels opening and closing, stepping motorstaking single steps) - Mimicking nanodevices that mimic biological functions may become basis for technological breakthroughs and curing of disease in 21st century

6. 2. Basic Equation of Animal Life + H2O + heat + Internal mixing & delivery; + Food searching & capture avoidance + Metabolic sensing & control; + Cell repair & pathogen surveillance

7. Biological monomers and polymers

8. 3. Division of labor among cell organelles in single cell organisms (e.g., paramecium)

9. Compendium of structure and function of cell organelles

10. 4. Division of labor among organ systems of mammals

11. 5. Governing principles of organism’s function(a) Homeostasis = internal steady state • (a) In organisms consisting of several organ systems these systems share functions to contribute to a “constant” internal environment (or “sea within us”) called the interstitial fluid (ISF). ISF is filtered from blood plasma, bathes all cells, and then is retrieved back to blood plasma. This provides metabolic and ionic stability of local cell environment (a) reducing general housekeeping functions of most cells and (b) freeing highly differentiated cells for more specialized functions (electrical impulse conduction in neurons, contraction in muscles, secretion and reabsorption of fluid in epithelial cells such as the lining of the gut)

12. Kidneys conserve or waste water depending on body needs. Drinking large quantities of water -> increased H2O content (decreased osmolarity) of ISF -> reduced stimulus for vasopressin secretion by supraoptic nucleus of the hypothalamus -> decreased reabsorption of H2O by kidneys (wasting of water)-> restoration of normal ISF water concentration Claude Bernard: The stability of the “milieu interieur” (ISF), …..namely water, salt, nutrient and oxygen contents, … (within 5-10%)…..under the regulation of the nervous system ……. is the primary condition for the independent of existence of animals……in a wide variety of external environments… Walter Cannon: term “homeostasis”

13. b. Constant feedback corrections of ISF metabolic (e.g., glucose) contents push-pull (or yin/yang) system for endocrine control of blood glucose: insulin release in response to high plasma glucose -> uptake of glucose by muscle and liver and conversion to storable polymer glycogen; glucagon release in response to low plasma glucose -> breakdown of glycogen stores and glucose release into plasma

14. c. early integration of response to threatening stimulus -> generalized stress response including coordination by brain of autonomic (involuntary) sympathetic nervous system “Rest and digest” in nonstressed organism or recovery of organism from stress response “Fright, flight or fight” response

15. d. Defense of existing function of cells and renewal of function by cell replacement serve as hedge against parasitism and agingDefense as local feature (innate = production of natural antibiotics & recruitment of white blood cells that engulf and digest invader organisms) or part of circulating surveillance system (adaptive = specific antibody production) Lining of digestive system: cells mature as the move up the villi of the gut lining to replace worn out cells

16. e. What all cells must do for themselves 1. Maintain an adequate supply of “free energy currency” (ATP) to fuel organelle synthesis and function 2. Maintain plasma membrane integrity (lipid bilayer with transmembrane or peripherally attached proteins) and as well as renewal of intracellular nanodevices 3. Maintain the constant ionic composition of its intracellular fluid (ICF), which is K + organic anion based vs. ISF, which is Na + Cl based). 4. Maintain signaling and response apparati to allow communication with adjacent and distant cells (ion channels and second messenger systems). 5. Maintain motors that move organelles (membrane bound compartments such as mitochondria) around the cell and provide for changes in cell shape.

17. b. Evolution: stability vs “tweaking” of function 1. All cells have similar lipid bilayer plasma membranes, similar genetic code, similar complex metabolic pathways (enzyme clusters), and similar apparatus for protein synthesis (mRNA attaching to chain of ribosomes). Modification of extant nanodevices for changing function rather than de novo design of novel ones. (e.g., Mitochondria are simple bacteria that were long ago taken up into nucleated cells by invagination of plasma cell membrane and now live as symbionts. 2. To accommodate to changes in environment, organisms “tweak” established organ structure to provide for new function Ex. Increased no. of acid secreting kidney cells on change to high animal protein diet vs increased no. bicarbonate secreting cells on change to vegetarian diet