IPHY 4440 1st Edition Lecture 3 Outline of Last Lecture I. Patterns of bioregulator secretionOutline of Current Lecture II. Equilibrium chemical reactionsIII. Target CellsIV. Physiological Levels vs. Pharmacological V. Biological Half-lifeVI. Chemistry of bioregulatorsVII. Dose response relationshipsVIII. Synthesis of BioregulatorsCurrent LectureI. Equilibrium chemical reactionsa. A + B  C1) Reaction can go either way2) A and B acting as the hormone and its receptor3) More A + B will favor the forward reaction4) Less A + B will favor the reverse reactionII. Target Cells a. Specific protein receptor (R)1) Receptors are always proteins2) When receptors are bound= Ligand3) Binds a specific bioregulator or a ligand (L)4) When a receptor is occupied (Ro)5) L + R   (Ro) = (L-R) 6) (L-R)= ligand receptor bound complexb. (Ro) facilitates the response in target cellc. R may be on the cell membrane or may be free in cytosol or nucleus3 roles1) Causes an enzymatic activation2) Opens ion channels in the cell membrane3) Activates transcription factors (act on DNA or nucleus)d. Target cell characteristics1) Lock and key fitThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.2) Must have affinity for bioregulator3) Hormones act at very low levels therefore there must be receptors for those low levels III. Physiological Levels vs. Pharmacological a. Physiological levels1) pg/mL (picogram/mL) or ng/mL (nanogram/mL)  hormone size level present in the blood2) Picogram is as small as a paperclipb. Pharmacological level1) mg/mL or microgram/mL (ug/mL)  1000 to 1,000,000X greater than the physiological levels 2) Pharmacological means in a disease state, hormones can reach that levelKey point: always test bioregulators at multiple doses IV. Biological Half-lifea. Determined by two things1) Metabolism rate (inactivation) aka signal removed 2) And/or excretion rates- Breakdown of a hormone is a good thingb. Blood level of a hormone = result of secretion and removal rates - Balance that determines about how much of that hormoneremainsV. Chemistry of Bioregulators Characterized by their chemistrya. Majority in this course: peptides, steroids, thyroid hormones b. Will see a few proteins and biogenic aminesVI. Dose response relationshipsa. A pharmacological dose produces a biological level that exceeds naturally occurring levels which is intentional for clinical and research settingsb. Example: bioregulators that have effect at pharmacological levels will have different effects at physiological levels and have different response at each levelc. Massive overdoses of those hormones, why? Weak binding effectsd. Difference responses to an increase in dosage1) Responses may start to plateau at higher levels because they are no more receptors able to bind, max out receptors, or low level of receptors for some hormones2) Responses may reach an optimal dose at a higher dose  stronger the effect at optimal dose then the response suddenly diminishes due to the overstimulation. Also the receptors may desensitize/down-regulate receptorsor may just be toxic 3) Responses may have different bioregulators that have different optimal dosesVII. Synthesis of Bioregulatorsa. Secretion= Synthesis + release (time from synthesis to release may take some time)b. Bioregulators that are synthesized from precursors may either release or store before releasing1) If the bioregulator stores before releasing then it has a quicker response to stimuli, very important factor 2) If the bioregulator does NOT store before releasing then it takes a longer amount of time to react or respond c. Synthesis of proteins and peptides 1) Synthesized from amino acids into FSH or LH or a peptide such as vasopressin, first stores then release2) Note: vasopressin is a hormone from pituitary important for pressured. Synthesis of DNA1) RNA (splice variants)  mRNA polypeptides  proteins or peptides2) Splice variants can produce multiple products from 1 DNA moleculee. Synthesis of Thyroid Hormones1) Amino acid (tyrosine)  thyroid hormones (T3 & T4)  storage  releasef. Synthesis of Steroids (lipids)1) Cholesterol  Steroids (androgens, estrogens, progestogens, mineralocorticoids, glucocorticoids)  releaseg. Synthesis of Eicosanoids1) Arachidonic acid  eicosanoids