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