biochemical endocrinology
TRANSCRIPT
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Overview of Biochemical Endocrinology
Endocrinology is concerned with the study of thebiosynthesis, storage, chemistry, and
physiological function of hormones and with the
cells of the endocrine glands and tissues thatsecrete them.
Definition of Biochemical Endocrinology
The study of the chemistry of endocrine hormonesin living organisms.
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Hormone- "chemical substance secreted by aductless gland into blood that is transported to adistant target organ whose activity it specifically
affects".
Target Tissues- have receptors or specific binding
proteins for each hormone
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Properties of Hormones:
1. They are biosynthesized.2. They operate at vanishingly small
concentrations in blood (10-12 to 10-8 M,
nano-pico).3. They have short half lives.
4. They often exert multipoint control and
operate at a number of target organs;hormones awaken existing potential in targetcells that are preprogrammed to respond.
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5. They are feedback regulated by: (a)themselves, (b) the product(s) of their
action, (c) the central nervous system.
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Chemistrys
There are several chemically distinct classes of hormones:amine(epinephrine), peptide (insulin, glucagon) and steroid
(cortisol).
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Insulin, Glucagon, Epinephrine and Cortisol are theHormones that Control Glucose Homeostasis:
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Hormone Receptors:
Interaction between hormone and receptor forms the "hormonereceptor complex".
Strength of binding is expressed as the dissociation constant Kd,the concentration at which the binding sites are half-saturated.
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Classification of Hormones by Receptor Properties:
Group I: Hormones that bind to intracellular receptors:Glucocorticoids, mineralocorticoids, estrogens, progestins,
androgens, vitamin D, thyroid, retinoic acid
Group II: Hormones that bind to cell surface receptors:
Group IIA: The second messenger is cAMP: vasopressin, glucagon,F-adrenergic catecholamines, somatostatin, opioids.
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Group IIB: The second messengers are IP3 (inositol trisphosphate) / Ca2+
and diacylglycerol (DAG): oxytocin, angiotensin II, E-adrenergic
catecholamines.
Group IIC: The cell surface receptor posses tyrosine protein kinaseactivity (intracellular messenger unknown): insulin, growth factors.
Group IIC': The cell surface receptor recruits soluble tyrosine kinases:growth hormone.
Group IID: The second messenger is cGMP: atrial natiuretic peptide(ANP).
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General Features of Hormone Classes, Group I and Group II:
Feature Group I Group II
Solubility Lipophilic Hydrophilic
Plasma T1/2 Long (Hours to Days) Short (Minutes)
Receptor Location Intracellular Plasma Membrane
Signal Mediator Receptor-Hormone Comp. cAMP,cGMP,Ca2+,IP3,DAG
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Steroid / Thyroid / Retinoic Acid Hormone Actions:
Group I- lipophilic, derived from cholesterol (except thyroid andretinoic acid)
Passively diffuse through the plasma membrane of the target cell toassociate with their receptors.
The hormone-receptor complex is assumed to be the intracellularmessenger
Effects of these hormones are quite specific.
Cell Surface Acting Hormone Action:
Group II: peptide and amine hormones bind to membrane spanningreceptors (7 transmembrane); communicate through secondmessengers, cAMP (Group IIA) or Ca2+ / IP3 / DAG (Group IIB).
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G-Proteins
Review
E = The Effector Protein, Adenylate CyclaseR = Receptor, 7-transmembrane cell surface receptor
Note: once the Effector protein is active the second messenger c-AMP is
produced activating Protein Kinase A and starting a "cascade" of events leadingto transmission of message and physiological / biochemical responses.
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Hormones Functioning via IP3 / Ca2+ and DAG:
PIP2 = Phosphatidylinositol-4,5-bisphosphate
IP3 = Inositol-1,4,5-triphosphate
DAG = Diacylglycerol
PLC = Phospholipase C
PKC = Protein Kinase C
CaM Kinase = Calmodulin Kinase
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[1] hormones bind to receptor
[2] receptor is coupled to phospholipase C by Gp
[3] Phospholipase C splits PIP2 into IP3 and DAG
[4] and [5] IP3 mobilizes intracellular (stored) Ca2+ from the ER foractivation of CAM
[6] and [7] DAG activates protein kinase C which is further activatedby Ca2+
[8]the concerted action of these two kinases elicit cellular responses
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FIGURE 16-6 Diagrammatic overview of biochemical events in mast-cell activation and
degranulation. Allergen crosslinkage of bound IgE results in FcRI aggregation and
activation of protein tyrosine ki- nase (PTK).
(1) PTK then phosphorylates phospholipase C, which converts phosphatidylinositol-4,5bisphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3).
(2) DAG activates protein kinase C (PKC), which with Ca2+is necessary for microtubular
assembly and the fusion of the granules with the plasma membrane. IP3is a potent
mobilizer of intracellular Ca2+stores.
(3) Crosslinkage ofFcRI also activates an enzyme that converts phosphatidylserine (PS)
into phosphatidylethanolamine (PE). Eventually, PE is methylated to form
phosphatidylcholine (PC) by the phospholipid methyl transferase enzymes I and II (PMT I
and II).
(4) The accumulation of PC on the exterior surface of the plasma membrane causes anincrease in membrane fluidity and facilitates the formation of Ca2+channels. The resulting
influx of Ca2+ activates phospholipase A2, which promotes the breakdown of PC into
lysophosphatidylcholine (lyso PC) and arachidonic acid.
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Clinical Correlate
Bacterial Toxins:
Cholera Toxin
Symptoms: watery stools, vomiting, cyanotic, low blood pressure, rapid / weak
pulseTreatment: IV solution of elctrolytes, tetracycline
Cause: cholera toxin inhibits GTPase preventing breakdown of GTP to GDPand locking the E subunit in the activated state producing a continuousoversupply of cAMP
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THANK
S