Aksi hormon yang meregulasi metabolisme bahan bakar tubuh .Reseptor insulin...

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Transcript of Aksi hormon yang meregulasi metabolisme bahan bakar tubuh .Reseptor insulin...

Aksi hormon yang meregulasimetabolisme bahan bakar tubuh

Dr. Syazili Mustofa, M.BiomedLektor mata kuliah ilmu biomedik

Departemen Biokimia, Biologi Molekuler, danFisiologi

Fakultas Kedokteran Unila

Hormon yang mempengaruhimetabolisme bahan bakar di tubuh

Anabolik (Insulin) mempromosikanpenyimpanan nutrien ( glikogen di hati, Triasilgliserol di jarangan adiposa) danmenstimulasi sintesis protein di otot

Lawan insulin (Counterregulatory Hormone)memobilisasi bahan bakar ( memicuglikogenolisis dan glukoneogenesis) Glukagon , Epinephrine, norepinephrine, cortisol,

somatostatin, growth hormone Thyroid hormone

INSULIN

- disintesis oleh sel beta pankreas- mengandung dua rantai polipeptida

rantai A dihubungkan oleh 2 jembatansulfida antara A7 B7 dan

A20 B19 rantai B

pada rantai A terdapat jembatan sulfida A6 A11

Biosintesis dan Struktur Insulin

Reseptor insulin Glikoprotein membran sel yang terdiri dari 2 sub bagian

Memiliki aktivitas kinasetirosinUrutan prosesnya :

Insulin terikat sub bagianalfaSub bagian beta teraktivasidengan sendirinya melaluiautofosforilasiFosforilasi IRS-1 dan IRS-2Hasilnya :

1. Jalur mitogenik2. Jalur Metabolik

Mekanisme kerja insulin

Tempat kerja utama insulin(+) = dirangsang olehinsulin(-) = dihambat olehinsulin

INSULIN

efek fisiologis nya :

* merangsang penyimpanan glikogen di hati danotot

* merangsang pembentukan asam lemak dantriasil gliserol serta penyimpanannya di adiposa

Physiological effect of insulin

* merangasng sintesis lebih dari 50 jenis protein sebagain berhubungan dengan pertumbuhanorganisme.

* punya efek parakrin, insulin menekan produksiglukagon pada sel alfa pankreas

GLUCAGON* synthesized as part of large precursor

protein (proglucagon).* Proglukcagon produced by

- cell of the Langerhans islet of the pancreas

- Intestine L cells

* contain several peptides linked as tandem with :

- glisentin peptida linked to-glisentin (glycentin-related peptide)

- glucagon peptida linked to glukagon I(GLP-1)peptida linked to glukagon II(GLP-2)

Struktur glukagon

GLUCAGON* stimulate glycogenolisis, gluconeogenesis &

ketogenesis by stimulate synthesis cAMP in side the targeted cells.* Liver the main targeted organ* Stimulate the release of Insulin from cell of the pancreas

Somatostatin (growth hormone-inhibiting hormone, somatotropin

release-inhibiting factor, GHIH, SRIF)) hormon peptida berpengaruh terhadap transmisi sinyal saraf dan

perkembangan sel tubuh. GHIH mempunyai dua bentuk dari irisan sebuah

preproprotein, satu dengan 14 asam amino dan 28 asamamino.

GHIH disekresi oleh beberapa organ antara lain lambung, usus, sel delta pankreas,[dan neuron (sel saraf)dari nukleusperventrikular dari hipotalamus, kelenjar hipokampus danbatang otak pada bagian nucleus tractus solitarii.

GHIH adalah sebuah hormon inhibitor yang antagonisterhadap GHRH dalam proses sekresi GH.

SOMATOSTATIN* Precursor praprosomatostatin,

peptide that consist of 116 AA

* Two kind of prosomatostatin :- S-14 cyclic peptide, 14 aa, BM 1600

produced in hipothalamus, sel of Langerhans islet, Central nervous system& in stomach & duodenum cells

- S-28 more potent 7-10 times inhibite the release of GH & insulin

SOMATOSTATIN

* its secretion is stimulated by :- metabolites: glucose, arginine & leusin.- hormon adl : glucagon, vasoaktif intestine

peptide(VIP), Cholecystokinin (CCK)

SOMATOSTATIN

* Physiological effect :- supress the secretion of GH & TSH

(thyroid- stimulating hormone) from Hipofisis anterior

- supress the secretion of insulin & glucagon

Struktur Somatostatin

* Physiological effect

- decrease the absorption of nutrient from intestine for delay the time to emty the stomach by :

. Gastrin secretion & gastric acid

. Decrease the pancreatic exocrine(ie. digestive Enz, bicarbonate, & water

. Decrease blood flow in the splanknik area

CATECOLAMIN(Epinephrin, Norepinephrin, Dopamine)

* are product secreted by sympatoadrenal system

to adapt againts acute and chronic stress.

* Storaged in the form- Epinephrin (80-85%) synthesized in theadrenal medulla

- norepinephrin (15-20%) synthesis & storaged in

. adrenal medulla

. CNS

. The end of adrenergic nervous system

- Dopamine act mainly as aneurotransmiter

metabolic effect in fuels is small

CATECOLAMIN* Synthesized from thyrosin (its precursor)* secretion of epinefrin & norepinefrin dirangsang

by severals stres including- pain- bleeding- exercise- hypoglicemia- hypoxia

stress

Transmission of the Nervous impuls

Acetyl cholin

Depolarisazation of plasma membran

Ca2+ extracell

Ca2+ intracell

cyitosol

Synthesis & release of the epinephrin & norepinephrin

Release catecolamine

PHYSIOLOGICAL EFFECT of CATECOLAMIN* act through 2 kind of main receptors in targeted cell ie :

- -adrenergic receptor- -adrenergic receptor

* action of epinephrin & norepinephrin in :- liver influence directly on fuels metab- adipocyte- sceletal muscle. - & pancreatic cells

CATECOLAMIN (Epinefrin & Norepinefrin)

* Hormone that act conversely/ againts Insulin action

* create metabolic effect toimmobilyzed the fuel to cell that need

energy when prone to acute and chronic stresses

Efekepinefrin

Menstimulasi: glikogenolisis di

hati dan otot Glukoneogenesi

s di hati Lipolisis di

adiposas

* Both simultanly supress secretion of insulin make sure that fuel flow will continue to using do not storing during stimulation of stress

* effect in heart & vasculer increase blood flow & systemic blood pressure

CATECOLAMIN(Metabolism & inactivation)

* have affinity relatively low to the & receptors

after binding quickly release (free katekolamin) duration of the biological response is

short.

* 2 kind of inactivation

1. Free catecolamin was reabsorp by end of adrenergic nervous can be reused/ resecreted then can be:

- deaminated by monoamin oksidase (MAO)

- or metilated by katekol O-metiltransferase (COMT) 3- metoxy-4-hidroximandelic acid (inside the end nervous) released to the circulation.

Liver and kidney could absorp catecolamin in the blood by enzymes: MAO & COMT

3-metoksi-4-hidroksimandelic acid (vanililmandelic acid / VMA)

Free catecolamin will be inactivated by conjugation process in pathological condition ( neoplasma

medula adrenal ) increase the release of Epinephrin & norepinephrin ( overexpress)

it can be measured: catecolamin or its metabolite (VMA)

GLUCOCORTICOID (GC)* The main physiological GC in the body is

Cortisol (hydrocortison)* steroid precursor : Cholesterol

A B

CD

siklopentanoperhidrovenantren

GLUCOCORTICOID* synthesis & secretion are controlled by signal

cascade: nervous & endocrine that sequentially carried in cerebrocortex-hipothalamus-hipofisis-adrenocortex axis.

* Stress signal trigger the systhesis of monoamin (setil choline & serotonin) stimulate synthesis & release of CRH

(corticotropin-releasing hormone) enter the blood vessel of porta -

hipothalamus-hipofisis

Adrenal gland

Pengaturan sekresi kortisoll

* CRH flow to specific receptor in ant hypophysis cell membrane

H-R complex stimulate the secretion of ACTH (adreno

corticothropic) into systemic circulation flow to spec. receptor in cortex adrenal

cell membran H-R complex stimulate Cortisol secretion

Cholesterol (C27)

HO5

432

1

678

910

141311

12

1516

17

19

25

21

2018

22

27

24

23

26

Pregnenolon (C21)

HO

C=O

CH3

HO

C=O

CH3

Progesteron (C21) Cortisol (C21)

HO O

C=O

CH2OH

HOOH

Efek kortisol

free kortisol in the blood as negative feedback signal to secretion of CRH & ACTH cortisol - supress secretion of CRH &

ACTH cortisol - stimulate secretion CRH &

ACTH

PATHOLOGIC CONDITION- Cushing Syndrome

Secretion of kortisol excessive caused by ACTH secretion excessive.

. Hipercortisolemia caused by benign adenoma (tumor) producingACTH in the anterior hipofisis gland

. This tumor produce ACTH autonomically (do not influenced by normal cortisol negative feedback)

- Cushing Syndr. Tumor in the adrenal cortex

hipersecretion of cortisol kdr kortisol in the blood

. If level of kortisol & , the tumor may be in the anterior hipofisis.

Physiological effect GC in tissues* inhibit synthesis of DNA, RNA & protein and

stimulate degradation those makromolekul.* act to make sure the energy fuel is available as

response to chronic stress-* Bila GC glucose absorption by cell in tissues

inhibited, cause:

- lypolisis in. adipocyte- proteolisis in skin, lymfoid cell &

muscle FA released will be oxydized by the liver to

produce energy

glycerol & AA act as substrate to