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BIOCHIMIA HORMONILOR BIOCHIMIA HORMONILOR 

CURS 1CURS 1

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A hormone (from Greek ὁρμή, "impetus") isa chemical released by a cell, a gland, or an

organ in one part of the body that aectscells in other parts of the organism! nly asmall amount of hormone is re#uired toalter cell metabolism! $n essence, it is achemical messenger that transports a signalfrom one cell to another!

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%ypothyroidism

%yperthyroidism

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&ushing disease

Addison disease

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Acromegaly

Gro'th hormone deciencyand gigantism

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heochromocytoma(tumor of the medulla of the adrenal glands )

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&ytostatic * +amoifen is an antagonist of the estrogen receptor

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-ethod of measuring hormones

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CatecholaminesCatecholamines

(Adrenalin, Noradrenalin, Dopamine(Adrenalin, Noradrenalin, Dopamine

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&atecholamines&atecholamines

•.iologically*acti/e 'ater*soluble amines deri/edfrom tyrosine that ser/e as neurotransmitters in the&01 and as hormones in circulation in response topsychological stress (2ght or 3ight response4) orhypoglycemia5

•All three and are produced in chroma6n cells ofthe adrenal medula of the sympathetic ner/oussystem and and post*ganglionic bers of the

sympathetic di/ision of the autonomic ner/oussystem!•7opamine also acts as a neurotransmitter in the&01 and is synthesi8ed by neuronal cell bodies ofthe substantia nigra and /entral tegmental area inthe midbrain (as 'ell as serotonin)

9pinephrine (adrenaline)

0orepinephrine (noradrenlaine)7opamine

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.iosynthesis of&atecholamines

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1ynthesis of &atecholamines1ynthesis of &atecholamines

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•+yrosine hydroylase is the rate*limitingstep•7A decarboylase is a pyridoal*:;*phosphate*dependent en8yme•7opamine β*hydroylase is a &u*diastereometric

sympathomimetic amines of lo'er e6cacy•?asoconstriction and hypertensi/e acti/ity of ephedrine

and pseudoephedrine are through α*adrenergic receptors

1ynthesis of &atecholamines1ynthesis of &atecholamines

7egradation of7egradation of

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7egradation of7egradation of&atecholamines&atecholamines

•-onoamine oidase (-A) inacti/ates catecholaminesby oidati/e deamination to yield the correspondingaldehyde•&atechol**methyltransferase (&-+) also inacti/ates

catecholamines by methylation using 1*adenosylmethionine (1A-) as the one*carbon donor

•ne released, catecholamines ha/e a half*life of ca! >

min due to subse#uent inacti/ation

•-A inhibitors and methamphetamine blockcatecholamine degradation, allo'ing their accumulationin the presynaptic neuron and subse#uent leakage into

circulation, pro/iding an antidepressant action!

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$mportant fetures of catecholaminebiosynthesis, uptake and signaling

>! .iosynthesis

! Bptake(transporter)

C! @eceptor*mediatedsignaling

:! &atabolism

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+yrosine hydrogenase5 rate*limitingen8yme

>! +% is a homotetramer, each subunit hasm!'! of DE,EEE

3. Km  µ- rangeH saturation undernormal condition

C! &ofactor5 biopterinH competiti/einhibitor5 α*methyl* p*tyrosine

:! 1e#uence homology5 phenylalaninehydroylase and tryptophanhydroylase

D! hosphorylation at 0*terminal sites5

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7opa decarboylase

1! Co"actor# p$rido%ine& lo' Km )t hi*h Vmax 

+! Also decaro%$late -H./ and other aromatic a!a!# aromatic amino acid decaro%$lase (AAAD

0! Inhiitor# α-meth$ldopa

7opamine β*hydroylase

1! Co"actor# ascorate& s)strate# dopamine

+! Inhiitor# dieth$ldithiocaramate (copper chelator

0! DBH is a tetrameric *l$coprotein (2Da and 02Da

3! Store in the s$naptic 4esicle and releasale

henylethanolamine 0*methyltransferase(0-+)S)strate# S-adenos$lmethionine& re*)lated $

corticosteroids

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-etabolism of dopamine

-aIor acidicmetabolites5

A! ,C*dihydroyphenylacetic acid(7A&)

.! %omo/allic acid

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$nacti/ation of 0orepinephrine

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-onoamine oidase (-A)

1! Co"actor# "la4in& located on the o)ter memrane o"

mitochondria

+! Con4ert amine into aldeh$de ("ollo'ed $ aldeh$de deh$dro*enase to acids or aldeh$de red)ctase to *l$col

0! MAO-A# N5 and -H. (inhiitor# clor*$line& MAO-B#

phen$leth$lamines (DA (inhiitor# depren$l3! /atient treated "or depression or h$pertension 'ith

MAO inhiitors# se4ere h$pertension a"ter "ood ta2en'ith hi*h amo)nts o" t$ramine (cheese effect)

&atechol**methyltransferase(&-+)1! 5n6$me can metaoli6e oth intra- or e%tracell)larl$

+! Re7)ires M*+8 and s)strate o" S-adenos$lmethionine

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&lassication of Adrenergic receptor

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Jeatures of Adrenergicreceptors

1! Both N5 and epinephrine ind toα

 andβ

 receptors

  β1 locates mainl$ in the heart and corte%& β+

predominate in the l)n* and cereell)m& β0 in the

adipose tiss)e (si*ni"icance in oesit$

3 β-receptor stim)lates AC& in t)rn, inacti4ates receptor

4ia βAR9 and β-arrestin

4 α1 is a post-s$naptic receptor (three s)t$pes# 1A, 1B

and 1D& 'hile α+ is oth post- and pre-s$naptic

receptor (three s)t$pes# +A, +B and +C

! Representati4e li*ands# propranolol (β anta*onist, 

$ohimine (α a*onist

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propanolol

yohimbine

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7ynamics of catecholaminereceptors

(up*regulation and do'n*regulation)

catecholamine receptor

a*onist

anta*onist