Overview of Biochemical Endocrinology

Overview of Biochemical Endocrinology

Endocrinology is concerned with the study of the

biosynthesis, storage, chemistry, and
physiological function of hormones and with the
cells of the endocrine glands and tissues that
secrete them.

Definition of Biochemical Endocrinology

The study of the chemistry of endocrine hormones
in living organisms.
Hormone- "chemical substance secreted by a
ductless gland into blood that is transported to a
distant target organ whose activity it specifically
affects".

Target Tissues- have receptors or specific binding

proteins for each hormone
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 target
cells that are preprogrammed to respond.
5. They are feedback regulated by: (a)
themselves, (b) the product(s) of their
action, (c) the central nervous system.
 Chemistrys

There are several chemically distinct classes of hormones:

amine(epinephrine), peptide (insulin, glucagon) and steroid
(cortisol).
Insulin, Glucagon, Epinephrine and Cortisol are the
Hormones that Control Glucose Homeostasis:
 Hormone Receptors:

Interaction between hormone and receptor forms the "hormone

receptor complex".
Strength of binding is expressed as the dissociation constant Kd,
the concentration at which the binding sites are half-
saturated.
 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,
b-adrenergic catecholamines, somatostatin, opioids.
Group IIB: The second messengers are IP3 (inositol trisphosphate) / Ca2+
and diacylglycerol (DAG): oxytocin, angiotensin II, a-adrenergic
catecholamines.

Group IIC: The cell surface receptor posses tyrosine protein kinase
activity (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).
 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

Steroid / Thyroid / Retinoic Acid Hormone Actions:
Group I- lipophilic, derived from cholesterol (except thyroid and
retinoic acid)
Passively diffuse through the plasma membrane of the target cell to
associate with their receptors.
The hormone-receptor complex is assumed to be the intracellular
messenger
Effects of these hormones are quite specific.
Cell Surface Acting Hormone Action:
Group II: peptide and amine hormones bind to membrane spanning
receptors (7 transmembrane); communicate through second
messengers, cAMP (Group IIA) or Ca2+ / IP3 / DAG (Group IIB).
G-Proteins
Review
E = The Effector Protein, Adenylate Cyclase
R = 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 leading
to transmission of message and physiological / biochemical responses.
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

[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 for
activation of CAM
[6] and [7] DAG activates protein kinase C which is further activated
by Ca2+
[8]the concerted action of these two kinases elicit cellular responses
FIGURE 16-6 Diagrammatic overview of biochemical events in mast-cell activation and
degranulation. Allergen crosslinkage of bound IgE results in Fc􏰂RI 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 of Fc􏰂RI 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 an
increase 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.
Clinical Correlate

Bacterial Toxins:
Cholera Toxin
Symptoms: watery stools, vomiting, cyanotic, low blood pressure, rapid / weak
pulse
Treatment: IV solution of elctrolytes, tetracycline
Cause: cholera toxin inhibits GTPase preventing breakdown of GTP to GDP
and locking the a subunit in the activated state producing a continuous
oversupply of cAMP
THANKS