catecholamine

Hormones that regulates fuel metabolism

Major hormonesAnabolic hormone

insulinCounter regulatory hormone

epinephrinenor epinephrineglucagoncortisolSomatostatinGrowth hormonethyroid hormone

CATCHOLAMINES

Not necessary for lifeRequired for adaptation to acute & chronic

stressResponse involves integrated adjustmentCatechol 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 diseaseA chronic progressive disorder

involuntry tremors, dec- motor power and control, muscular regidity,

postural instabilityDeficiency of dopamin in substantia nigraCatcholamine can not cross the B B BDopa is the treatment

2nd step = decarboxylation

In cytoplasmDopa comes out from mito- to cytoplasmRequires 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 oxygenaseA 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

PNMTMethyl group is donated by active

methionineInduced by glucocorticoidThis 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

Norepinephrine

+++++

++

Epinephrine ++++ ++++Relative effects of epinephrine and norepinephrine on and adrenergic receptors.

Guyton

Mechanism of Action 1. Catecholamine binds to β1 and β2Activates adenyl cyclaseIncreases cyclic AMPactivates c- AMP dependant protein

kinasePhosphorylates specific proteinsOn binding to α receptors (opposite of

above)2. Binds to α1Formation of IP3 & DAG or increase in ca+

+ as a second messenger.

Biochemical actionsIncreases blood glucose & lactate1, 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 actionBoth epi- & nor-epi breakdown of TG in

adipose tissue by increasing c-AMP(β effect), rapid release of FFA and Glycerol

Gluconeogenic actionEpinephrine(β2effect)

c-AMPSYNTHESIS OF KEY ENZYMES pyruvate- carboxylase PEP carboxykinase fructose 1 6 bi-phos

Action on glycolysisEpinephrine ----- LA productionNor-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

• paraganglioma – a catecholamine secreting tumour of the sympathetic paraganglia

adrenal pheochromocytoma (90%)

extra-adrenal pheochromocytoma

Signs and Symptoms of Pheochromocytoma

• treatment resistant hypertension (95%)

• headache• sweating• palpitations• chest pain• anxiety• glucose intolerance• increased metabolic rate

classic triad

Diagnosis and Treatment

• diagnosed by high plasma catecholamines and increased metabolites in urine

• no test for adrenal or extra-adrenal

• treatment is surgical resection