HORMONE SYNTHESIS, HORMONE SYNTHESIS, RELEASE AND TRANSPORTRELEASE AND TRANSPORT

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The hormones speak :The hormones speak :

We are the We are the chemical messengers chemical messengers of the body.of the body.

Diversified in our Diversified in our structure and structure and function;function;

Act either directly Act either directly or through or through messenger;messenger;

Growth, health, Growth, health, and welfare is our and welfare is our mottomotto The structure of insulinThe structure of insulin

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Intracelluler CommunicationIntracelluler Communication

All cells detect and respond to All cells detect and respond to environmental stimuli environmental stimuli

Intracelluler communication :Intracelluler communication :

- endocrine- endocrine

- nervous - nervous

- immune- immune Endocrine glands secrete Endocrine glands secrete

hormoneshormones

Hormone:Hormone:

produced in small amounts produced in small amounts by specific by specific tissues (endocrine tissues (endocrine glands), control the glands), control the metabolic metabolic and biological and biological activities in the activities in the target cellstarget cells

Active at low concentrations (picogram to nanogram)(picogram to nanogram)

HormoneHormone

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Categorized by site of synthesis1.Endocrine hormones2.Paracrine hormones3.Autocrine hormones

HORMONE CLASSIFICATION

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Categorized by Categorized by water solubilitywater solubility

1.1.Hydrophilic hormones /Hydrophilic hormones /The The water solublewater soluble hormones hormones

2.2.Lipohilic hormones /Lipohilic hormones /The The lipid lipid solublesoluble hormones hormones

HORMONE CLASSIFICATION

Categorized by Categorized by thethelocation of the location of the

receptorsreceptors1.1.Receptors on the Receptors on the

surface of the surface of the target cell, on target cell, on the plasma the plasma membrane membrane

2.2.Receptors in the Receptors in the intracellulerintracelluler

HORMONE CLASSIFICATION

HORMONE CLASSIFICATIONHORMONE CLASSIFICATION

Categorized by Categorized by chemical structurechemical structure

Protein and polypeptideProtein and polypeptide AmineAmine SteroidSteroid EicosanoidEicosanoid

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PEPTIDE HORMONESPEPTIDE HORMONES

Consist of specific amino acidsConsist of specific amino acids Synthesized as large precursor Synthesized as large precursor

proteinsproteins Stored in membrane-enclosed Stored in membrane-enclosed

compartmentscompartments HydrophillicHydrophillic

PEPTIDA INSULINPEPTIDA INSULIN

Di sintesa di Pulau Pankreas sebagaiDi sintesa di Pulau Pankreas sebagai preproinsulinpreproinsulin

Untuk sekresi disimpan di RESUntuk sekresi disimpan di RES→ → oleh oleh enzim mikrosomal dibelah enzim mikrosomal dibelah menjadi proinsulin sewaktu menjadi proinsulin sewaktu memasuki membran RESmemasuki membran RES

Proinsulin diangkut ke golgi Proinsulin diangkut ke golgi kompleks kompleks dikemas menjadi dikemas menjadi secretory granulessecretory granules

Di granula, C-Peptida dipisahkan Di granula, C-Peptida dipisahkan insulin disekresikaninsulin disekresikan

Protein and Polypeptide Hormones Protein and Polypeptide Hormones SynthesisSynthesis

: Peptide hormone synthesis and packaging

ProinsuliProinsulinn

InsulinInsulin

AMINE HORMONESAMINE HORMONES

Derived from the amino acid Derived from the amino acid tyrosinetyrosine

Includes thyroid hormones Includes thyroid hormones and catecholaminesand catecholamines

Stored until secretedStored until secreted

Thyroid gland produce T3 and Thyroid gland produce T3 and T4 hormonesT4 hormones

Iodide (IIodide (I--) actively transported ) actively transported into the follicle of thyroid into the follicle of thyroid gland gland

Oxidized to iodine (IOxidized to iodine (Ioo) by a ) by a peroxidaseperoxidase

Thyroid HormonesThyroid Hormones

Iodine attached to tyrosine Iodine attached to tyrosine within thyroglobulin chainwithin thyroglobulin chain

MIT, DITMIT, DIT MIT and DIT or 2 DIT MIT and DIT or 2 DIT

molecules coupled togethermolecules coupled together TSH via cAMP stimulates TSH via cAMP stimulates

hydrolyze Thydrolyze T33 and T and T4 4 from from thyroglobulin (inhibited by KI)thyroglobulin (inhibited by KI)

Thyroid Thyroid HormonesHormones

STEROID HORMONESSTEROID HORMONES

Precursor: CholesterolPrecursor: Cholesterol LipophillicLipophillic Immediately released from the Immediately released from the

cell following synthesiscell following synthesis

Hormon SteroidHormon Steroid

Korteks adrenal sintesis :Korteks adrenal sintesis :glukokortikoid, glukokortikoid, mineralokortikoid, sex steroidmineralokortikoid, sex steroid

Terutama dari kolesterol plasma Terutama dari kolesterol plasma (sebahagian kecil dari asetil koA)(sebahagian kecil dari asetil koA)

Kolesterol plasma dirubah Kolesterol plasma dirubah menjadi pregnenolon oleh enzim menjadi pregnenolon oleh enzim sitokrom P450sitokrom P450

(mitkondria atau RES)(mitkondria atau RES)

Hormon SteroidHormon Steroid

Hormon SteroidHormon Steroid

Kekhususan seluler :Kekhususan seluler :– sintesis mineralokortikoid sintesis mineralokortikoid

pada sel glomerulosa pada sel glomerulosa

18 hidroksilase dan 18 18 hidroksilase dan 18 hidroksisteroid dehidrogenase hidroksisteroid dehidrogenase hanya ditemukan pada sel inihanya ditemukan pada sel ini

Golongan Hormon SteroidGolongan Hormon Steroid

Protein TransportProtein Transport

Thyroid HormonesThyroid Hormones

Globulin alfa (85%)Globulin alfa (85%)TBGTBG TBPA (transferitin)TBPA (transferitin) Albumin sedikitAlbumin sedikit

Protein TransportProtein Transport

Hormon SteroidHormon Steroid

KortisolKortisol- 75 % terikat CBG (transkortin)- 75 % terikat CBG (transkortin)- 10 % kortisol bebas- 10 % kortisol bebas- selebihnya pada albumin - selebihnya pada albumin (mis deksametason)(mis deksametason)

Protein TransportProtein Transport

Hormon SteroidHormon Steroid

AndrogenAndrogen- DHEA terikat lemah pada albumin- DHEA terikat lemah pada albumin- Testoteron terikat pada globulin - Testoteron terikat pada globulin spesifik ( SHBG)spesifik ( SHBG)

MineralokortikoidMineralokortikoid- tidak punya protein pengangkut - tidak punya protein pengangkut spesifikspesifik- membentuk ikatan lemah dengan - membentuk ikatan lemah dengan abuminabumin

EICOSANOIDS HORMONEEICOSANOIDS HORMONE

Produced from arachidonic acid, Produced from arachidonic acid, Released from phospholipids by action Released from phospholipids by action

of phospholipase Aof phospholipase A2, 2, phphososphpholipase Colipase C Produced in almost every organProduced in almost every organ In one pathway arachidonic acid is In one pathway arachidonic acid is

converted to prostanoids by a group of converted to prostanoids by a group of enzymes, the cyclooxygenase systemenzymes, the cyclooxygenase system

A second pathway to produce A second pathway to produce leukotrienes by the enzyme 5 leukotrienes by the enzyme 5 lipoxygenaselipoxygenase

EICOSANOIDS HORMONEEICOSANOIDS HORMONE

ProstaglandinsProstaglandins

SAIDS inhibit action of SAIDS inhibit action of phospholipasephospholipase

NSAIDs, such as aspirin and NSAIDs, such as aspirin and derivatives of ibuprofen, inhibit derivatives of ibuprofen, inhibit cyclooxygenase activity of PGH2 cyclooxygenase activity of PGH2 SynthaseSynthase

They inhibit formation of They inhibit formation of prostaglandins involved in fever, prostaglandins involved in fever, pain, & inflammationpain, & inflammation

They inhibit blood clotting by They inhibit blood clotting by blocking thromboxane formation blocking thromboxane formation in blood plateletsin blood platelets

REFERENCESREFERENCES

Devlin T M, PhD. Text Book of Devlin T M, PhD. Text Book of Biochemistry with Clinical Biochemistry with Clinical Correlations 5thed. Wiley-Liss, New Correlations 5thed. Wiley-Liss, New York. 2002 : 906-952, 982-983York. 2002 : 906-952, 982-983

McKee Trudy, McKee James R. The McKee Trudy, McKee James R. The molecular basis of Life. 3rded. molecular basis of Life. 3rded. McGraw-Hill. Americas, New York. McGraw-Hill. Americas, New York. 2003 : 541-5592003 : 541-559

Murray R K, et al. Murray R K, et al. Harper’s Harper’s Biochemistry 26thed. Appleton & Biochemistry 26thed. Appleton & Lange. America 2003: 434-473Lange. America 2003: 434-473

Raff A, et al. Moleculer Biology of The Raff A, et al. Moleculer Biology of The Cell. 4thed. Garland Science. New Cell. 4thed. Garland Science. New York. 2002: 832-892York. 2002: 832-892

Stryer L. Biokimia. Edisi 4. EGC, Stryer L. Biokimia. Edisi 4. EGC, Jakarta. 2000.: 340-358Jakarta. 2000.: 340-358