HORMONE SYNTHESIS, RELEASE AND TRANSPORT Departement of Biochemistry Faculty of Medicine USU HORMONE SYNTHESIS, RELEASE AND TRANSPORT

BIOCHEMISTRY MEDICAL FACULTY USU The hormones speak : We are the chemical messengers of the body. Diversified in our structure and function; Act either directly or through messenger; Growth, health, and welfare is our motto The structure of insulin BIOCHEMISTRY MEDICAL FACULTY USU

Intracelluler Communication All cells detect and respond to environmental stimuli Intracelluler communication : - endocrine - nervous - immune Endocrine glands secrete hormones BIOCHEMISTRY MEDICAL FACULTY USU BIOCHEMISTRY MEDICAL FACULTY USU

Hormone Hormone: produced in small amounts by specific tissues (endocrine glands), control the metabolic and biological activities in the target cells Active at low concentrations (picogram to nanogram)

HORMONE CLASSIFICATION Categorized by site of synthesis Endocrine hormones Paracrine hormones Autocrine hormones BIOCHEMISTRY MEDICAL FACULTY USU

HORMONE CLASSIFICATION Categorized by water solubility Hydrophilic hormones /The water soluble hormones Lipohilic hormones /The lipid soluble hormones BIOCHEMISTRY MEDICAL FACULTY USU BIOCHEMISTRY MEDICAL FACULTY USU

HORMONE CLASSIFICATION Categorized by the location of the receptors Receptors on the surface of the target cell, on the plasma membrane Receptors in the intracelluler BIOCHEMISTRY MEDICAL FACULTY USU

HORMONE CLASSIFICATION Categorized by chemical structure Protein and polypeptide Amine Steroid Eicosanoid

BIOCHEMISTRY MEDICAL FACULTY USU

PEPTIDE HORMONES Consist of specific amino acids Synthesized as large precursor proteins Stored in membrane-enclosed compartments Hydrophillic

PEPTIDA INSULIN Di sintesa di Pulau Pankreas sebagai preproinsulin Untuk sekresi disimpan di RES → oleh enzim mikrosomal dibelah menjadi proinsulin sewaktu memasuki membran RES Proinsulin diangkut ke golgi kompleks  dikemas menjadi secretory granules Di granula, C-Peptida dipisahkan  insulin disekresikan

Protein and Polypeptide Hormones Synthesis : Peptide hormone synthesis and packaging

Proinsulin Insulin

AMINE HORMONES Derived from the amino acid tyrosine Includes thyroid hormones and catecholamines Stored until secreted

Thyroid Hormones Thyroid gland produce T3 and T4 hormones Iodide (I-) actively transported into the follicle of thyroid gland Oxidized to iodine (Io) by a peroxidase

Thyroid Hormones Iodine attached to tyrosine within thyroglobulin chain  MIT, DIT MIT and DIT or 2 DIT molecules coupled together TSH via cAMP stimulates hydrolyze T3 and T4 from thyroglobulin (inhibited by KI)

STEROID HORMONES Precursor: Cholesterol Lipophillic Immediately released from the cell following synthesis

Hormon Steroid Korteks adrenal sintesis : glukokortikoid, mineralokortikoid, sex steroid Terutama dari kolesterol plasma (sebahagian kecil dari asetil koA) Kolesterol plasma dirubah menjadi pregnenolon oleh enzim sitokrom P450 (mitkondria atau RES)

Hormon Steroid

Hormon Steroid Kekhususan seluler : sintesis mineralokortikoid pada sel glomerulosa  18 hidroksilase dan 18 hidroksisteroid dehidrogenase hanya ditemukan pada sel ini

Golongan Hormon Steroid

Protein Transport  Globulin alfa (85%)TBG  TBPA (transferitin) Thyroid Hormones  Globulin alfa (85%)TBG  TBPA (transferitin)  Albumin sedikit

Protein Transport Hormon Steroid Kortisol - 75 % terikat CBG (transkortin) - 10 % kortisol bebas - selebihnya pada albumin (mis deksametason)

Protein Transport Hormon Steroid Androgen - DHEA terikat lemah pada albumin - Testoteron terikat pada globulin spesifik ( SHBG) Mineralokortikoid - tidak punya protein pengangkut spesifik - membentuk ikatan lemah dengan abumin

EICOSANOIDS HORMONE Produced from arachidonic acid, Released from phospholipids by action of phospholipase A2, phospholipase C Produced in almost every organ In one pathway arachidonic acid is converted to prostanoids by a group of enzymes, the cyclooxygenase system A second pathway to produce leukotrienes by the enzyme 5 lipoxygenase

EICOSANOIDS HORMONE

Prostaglandins SAIDS inhibit action of phospholipase NSAIDs, such as aspirin and derivatives of ibuprofen, inhibit cyclooxygenase activity of PGH2 Synthase They inhibit formation of prostaglandins involved in fever, pain, & inflammation They inhibit blood clotting by blocking thromboxane formation in blood platelets

REFERENCES Devlin T M, PhD. Text Book of Biochemistry with Clinical Correlations 5thed. Wiley-Liss, New York. 2002 : 906-952, 982-983 McKee Trudy, McKee James R. The molecular basis of Life. 3rded. McGraw-Hill. Americas, New York. 2003 : 541-559 Murray R K, et al. Harper’s Biochemistry 26thed. Appleton & Lange. America 2003: 434-473 Raff A, et al. Moleculer Biology of The Cell. 4thed. Garland Science. New York. 2002: 832-892 Stryer L. Biokimia. Edisi 4. EGC, Jakarta. 2000.: 340-358