lecture 24 Flashcards
What are peptides
chains of specific amino acids
What are amines
Tyrosine derivatives
What are steroids
Cholesterol derivatives
What are Eicosanoids
Arachidonic acid derivatives. Usually
act as autocrine or paracrine signalling molecules, but
can act distally
What hormones are • Insulin, vasopressin, TSH, calcitonin etc
Peptides
What hormone are • a) Catecholamines (Adrenal Medulla)
• Adrenalin & noradrenalin
• b) Thyroid hormones
• Thyroxine & triiodothyronine
Amines: Tyrosine derivatives
What hormones are • Cortisol, aldosterone, oestrogen,
testosterone etc
Steroids:
• Adrenal cortex, gonads & placental hormones
What are the 4 families of eicosanoids
—the
prostaglandins, prostacyclins, the thromboxanes
and the leukotrienes
What solubility of peptide hormone
Hydrophilic (polar)
What syntheses peptide hormones
Rough ER,
Packaged in Golgi complex
Where are peptides stored
Secretory granules
How to secrete peptide hormone
exocytosis
How are peptide hormones transported
Free hormone: soluble
Where are the receptors of the peptide hormones
Surface of target cell
What action can peptide hormone cause
Ion channel changes or
Second messenger system
What produces insulin
Anabolic hormone produced in the pancreatic b
cells in times of excess nutrient availability
What is the main role for insulin
Allows the body to use carbohydrates as energy
sources and store nutrients
What does insulin target
Liver, muscle, adipose tissue
What are the functions of insulin
• Lowers blood glucose levels
• Increases facilitated diffusion of glucose into cells
• Increases conversion of glucose into glycogen
(glycogenesis)
• Increases uptake of amino acids and protein
synthesis
• Increases synthesis of fatty acids (lipogenesis)
• Slows glycogenolysis
• Slows gluconeogenesis
What are some insulin receptor
Example of enzyme-linked receptor (tyrosine kinase)
• Tyrosine phosphorylation triggers multiple pathways
What is the most important regulator of insulin secretion
glucose
What are all the factors controlling insulin secretion
• -b cells monitor levels of circulating metabolites • Glucose • Leucine & alanine • Amino acids have little effect in absence of glucose increase, but they double insulin release in combination with glucose • Neuronal & hormonal • Parasympathetic stimulation • CCK (cholecystokinin) • Gastric hormones stimulate an ‘Anticipatory’ release of insulin • Other hormones, eg glucagon, growth hormone, cortisol
What is the major stimulation of adrenalin or epinephrine release (catecholamine)
Stress
• Threat, noise, excitement, high
temperature
How are catacholamine synthesized
• The catecholamines are synthesised
in sequence from tyrosine
Does catecholamines have negative feedback
No negative feedback loop. Action is
stopped mainly by degradation as
hormones have a short ½ life
What is the solubility of tyrosine
Hydrophilic
Where are catecholamine synthesized
Cytosol
Where are catacholamine stored
Secretory (Chromaffin) Granules
How to secrete catacholamine
Exocytosis
How are catecholamine transported
As a Free Hormone and Bound to
Plasma Proteins
Where are the receptors for catecholamine
Surface of Target Cell
What does the catecholamine activate
Second Messenger System
Where are amine hormones produced
thyroid
What is the role of amine hormone
Regulate basal metabolic rate
What does amine cleaved into
Cleaved to form pro-hormone
Thyroxine (T4) & active
Triiodothyronine (T3)
What is the solubility of amine hormones
Lipophilic amines, but polarity of the iodine means active transport is required across cell membranes Lypophilic, but now known to be actively transported into cells by transporters (ATP-dependent carriers)
Where are amine hormones synthesized
Within large glycoprotein
thyroglobulin
Where are amine hormone stored
Stored as thyroglobulin in
colloid follicles
How are amine hormone excreted
exocytosis
How are amine hormone transported
Mostly bound to Plasma Proteins
thyroxin-binding globulin
Where is the receptor of amine hormone
Inside Target Cell
What does amine hormone do
direct effect on genes
What are the efffect of thyroid hormone
1. Increased metabolic rate 2. Increased oxygen consumption by mitochondria 3. Nutrients 4. Thermogenesis
How are T3 & T4 secretion regulated
negative feedback, • Thyrotropin releasing hormone (TRH) formed in hypothalamus • Response to blood levels T4/T3 • TRH is released into portal veins of hypothalamic-hypophyseal tract • Stimulates thyrotropes to release TSH into blood • TSH stimulates follicular thyroid cells to produce and secrete T3 & T4 • As levels of T3/T4 rise, negative feed back loops reduce synthesis of TRH in hypothalamus (long arm) and release of TSH in the anterior pituitary (short arm)
What are the prostanoid
prostagladins
thromboxanes
What is the function of eicosanoid, Prostaglandins
• vasodilators
regulate blood flow
What is the function of eicosanoid, Thromboxane A2
• induces platelet
aggregation
• promotes
vasoconstriction
What is the function of eicosanoid, Leukotrienes
- allergy involvement
- neutrophil chemo-attractant
- vascular permeability
Whare are steroid hormone derived from
cholesterol
What are some steroid hormones
1) adrenal cortex (cortisol, androgens & aldosterone) 2) ovaries (estrogen and progesterone) 3) testes (testosterone 4) placenta (estrogen and progestero
Where are steroid stored
Hormones Not Stored, Only Precursor
(Cholesterol) Stored
Stored (or its derivatives) in lipid droplets
within each steroidogenic or
How are steroids produced
. Produced through a series of enzymatic reactions Cholesterol to pregnenolone (rate limiting step). Each steroidogenic organ can produce only those steroid hormones for which it has a complete set of
what is the solubility of steroid
lipophilic
How are steroid secreted
diffusion
How are steroid transported
Mostly Bound to Plasma Proteins
Where is the receptor of steroids
Inside of Target Cell
What is the action of steroids
Direct Effects on Genes ® Production of New
Proteins
What is the function of cortisol
Metabolic Actions Corticosteroids
Maintains blood glucose levels during
fasting & increases blood glucose
during stress
What happens when there is an early fasting
Cortisol 1. Early fasting - defence against hypoglycaemia. • Increase plasma glucose • Liver Increased glucose output • Promotes gluconeogenesis, glycogenolysis & lipolysis
What happens during the late fasting stage
Cortisol
• build up of glycogen stores
What Anti-inflammatory actions can cortisol do
Inhibits arachidonic acid production and
prostaglandins
How are cortisol regulated
• Negative feedback regulation on pituitary and hypothalamus by cortisol • Long feedback loop on hypothalamus by ACTH • Short feedback loop
Where are oxytocin released
• Released by posterior pituitary
Oxytocin receptors are on smooth muscle cells
• mammary gland and uterine
What is the role in oxytocin
so acts as a neurotransmitter in bra
s
1. Promotes milk ejection (milk let down) during lactat
oli
2. Uterine contraction during parturition
How oxytoxin promote milk ejection
Milk initially secreted into alveoli (sacs) within mammary
gland
OCT stimulates contraction of myoepithelial cells (smooth
muscle cells) which surround alveoli
How oxytoxin cause uterine contraction
on
Important in cervical dilation & uterine contractions
After birth maintains haemostasis & evacuation of
placenta
how oxytocin is regulated
Positive Regulation of Oxytocin Secretion 1. Suckling • Neurogenic reflex to hypothalamus 2. Pregnancy and Parturition • Oxytocin receptors in uterus increase late trimester & during labour • Estrogen induced • Uterus stretching - --> more oxytocin released
What happens when there is a thyroid tumour
• Hyperthyroidism due to thyroid tumour – increased T3 & T
What benign pituitary tumour do to cortisol
• Increased cortisol due to benign pituitary tumour – Cushing’s disease
What is salbutamol made from
man-made
What is the function of salbutamol
Dilates airways
May increase heart rate
Synthetic molecule
What is atropine made from?
Plants
What is the function of atropine
Dilated pupils attractive Dry mouth, photophobia, hallucinations, death! Deadly Nightshade Atropa Belladonna
What does drugs affect
chemical & electrical signalling
What is agonist
Bind and
activate the receptor
What is Antagonists
Bind and DO NOT
activate the receptor
What is affinity
A quantifiable measure of the molecular
attraction to the receptor
what is pharmacokinetics
What will happen to
the drug in the body?
What is pharmacodynamic
What effect(s) will the drug have in the body?
What is dose
• Amount administered
– in vitro: dose ~ concentration
– in vivo: dose = concentration
What is concentration
- Amount in given volume
* Amount at molecular target
What is potency
• How much drug is needed for effect
– NOT the affinity
– NOT the size of the response
What is efficacy
Ability of a drug to activate the receptor
What does agonist mimic
endogenous molecules
What is the role of antagonist
inhibit endogenous molecules
What is the therapeutic range
optimise benefit/minimise risk
How does Parasympathetic Sympathetic work together
they will try to balance each other
