catecholamine

Hormones that regulates

fuel metabolism
Major hormones
Anabolic hormone
insulin
Counter regulatory hormone
epinephrine
nor epinephrine
glucagon
cortisol
Somatostatin
Growth hormone
thyroid hormone
 CATCHOLAMINES
Not necessary for life
Required for adaptation to acute & chronic stress
Response involves integrated adjustment
Catechol can not facilitate stress alone but aided by
others.
 are secreted and stored in the adrenal medulla and
released in response to appropriate stimuli
Responses to Stress
Synthesis release of Catecholamine
 Ist step = ring hydroxylation

•Tyrosine enter the mitochondria

•Rate limiting step and enzyme(TH), cu containing metalloprotein
•Function as oxidoreductase
•Requires THB as hydrogen donor
•Parkinson disease
Parkinson’s disease
A chronic progressive disorder
involuntry tremors, dec- motor power and control,
muscular regidity,
postural instability
Deficiency of dopamin in substantia nigra
Catcholamine can not cross the B B B
Dopa is the treatment
2nd step = decarboxylation

In cytoplasm
Dopa comes out from mito- to cytoplasm
Requires pyridoxal phosphate.
 α-Methyl dopa resembles L- dopa, a competitive
inhibitor (antihypertensive)
3rd step = side chain hydroxylation

Dopamine from cytosole enters in to chromaffin- cells

DBH , a mono oxygenase
A cu containing enzyme (cu is oxdized and reduced
back by vit-C)
Ascorbic acid as electron donor
4th step = N- methylation(cytoplasm)

Nor-epi comes out from granules in to cytoplasm

PNMT
Methyl group is donated by active methionine
Induced by glucocorticoid
This reaction does not occur in nerves
 Mechanism of Action

• receptor mediated – adrenergic receptors

• peripheral effects are dependent upon the

type and ratio of receptors in target tissues

Receptor  
Norepinephri ++++ ++
ne +
Epinephrine ++++ ++++
Relative effects of epinephrine and norepinephrine on  and  adrenergic receptors.
Guyton
Mechanism of Action
1. Catecholamine binds to β1 and β2
Activates adenyl cyclase
Increases cyclic AMP
activates c- AMP dependant protein kinase
Phosphorylates specific proteins
On binding to α receptors (opposite of above)
2. Binds to α1
Formation of IP & DAG or increase in ca++ as a
3
second messenger.
Biochemical actions
Increases blood glucose & lactate
1, glycogenolysis in liver & muscles
In liver through cyclic AMP dependant protein kinase mediated by two ways
. Through β2 receptors (similar to glucagon)
. Through α1 receptors
In muscles due to absences of g-6-pase does not directly inc- blood glucose, but
inc- blood lactate & pyruvate
β effect
No Glucagon effect
HEART MUSCLE
Increase in cyclic AMP
+ve inotropic effect

2, Stimulate ACTH formation glucocor gluconeogenisis

3, Epinephrine onβ cells through α-adrenergic cyclic AMP & insulin release
Lipolytic action
Both epi- & nor-epi breakdown of TG in adipose
tissue by increasing
c-AMP(β effect), rapid release of FFA and Glycerol
Gluconeogenic action
Epinephrine(β2effect)
c-AMP
SYNTHESIS OF KEY ENZYMES
 pyruvate- carboxylase
 PEP carboxykinase
 fructose 1 6 bi-phos
Action on glycolysis
Epinephrine ----- LA production
Nor-epinephrine---- little effect
Metabolism of the catecholamines by catechol-O-
methyltranferase (COMT) and monoamine oxidase
(MAO).
 Pheochromocytoma

• a catecholamine-secreting tumor of
chromaffin cells of the adrenal medulla
adrenal pheochromocytoma (90%)

• paraganglioma – a catecholamine
secreting tumour of the sympathetic
paraganglia
extra-adrenal pheochromocytoma
Signs and Symptoms of Pheochromocytoma

• treatment resistant hypertension (95%)

• headache
• sweating classic triad
• palpitations
• chest pain
• anxiety
• glucose intolerance
• increased metabolic rate
 Diagnosis and Treatment

• diagnosed by high plasma catecholamines

and increased metabolites in urine

• no test for adrenal or extra-adrenal

• treatment is surgical resection