Catecholamines Lecture for 2nd year MBBS by Dr Waseem
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Transcript of Catecholamines Lecture for 2nd year MBBS by Dr Waseem
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