BIOKIMIA HORMON

Yanti Rosita

FK UMP

LEARNING OBJECTIVES

• Mengetahui prinsip-prinsip sintesis hormon

• Untuk mengetahui aspek biokimia hormon

• Untuk mengetahui prinsip-prinsip katabolisme hormon

• Untuk mengetahui regulasi hormon

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HORMONDari Bhs Yunani : “horman” =

menggerakkanAdalah zat atau transmiter kimiawi yang disintesis oleh kelenjar, disekresikan ke dalam aliran darah untuk bekerja pada organ sasaranTempat hormon bekerja (sel target) td: - sel jar. tubuh - sel kelenjar lainDi sel target hormon menjalankan fungsi regulasi tertentu secara fisiologik dan biokimia

HORMON• Secara biologi hormon efektif dalam

jumlah yang sangat kecil dalam darah yaitu 10-15 hingga 10-9 mol/L

• Hormon jaringan (parahormon)- mencapai sel sasaran tidak melalui aliran darah- berpengaruh pada sel disebelahnya- contoh hormon pencernaan

klasifikasi

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Jenis-jenis Hormon

– Peptida dan protein

– Derivat asam amino

– Steroids – Derivat asam lemak : Eicosanoids

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Peptides and Proteins

• Glycoproteins from anterior pituitary:- TSH- LH- FSH

• Peptides and small proteins:- Digestive tract hormones- Pituitary hormones- Pancreatic hormones

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Peptides and Proteins

HORMONE SOURCE

1 FSHRF Hypothalamus

2 LRF Hypothalamus

3 GHRF Hypothalamus

4 TRF Hypothalamus

5 PRF Hypothalamus

6 CRF Hypothalamus

7 GIF Hypothalamus

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Peptides and ProteinsHORMONE SOURCE

1 ACTH Anterior hypophyse

2 TSH Anterior hypophyse

3 FSH Anterior hypophyse

4 LH Anterior hypophyse

5 LTH Anterior hypophyse

6 GH Anterior hypophyse

7 Vasopresin Posterior hypophyse

8 Oksitosin Posterior hypophyse

9 Insulin Β-pancreas cell

10 Glucagon Α-pancreas cell

11 Secretin Duodenum

12 Angiotensin Lever

Amino acid Derivatives

• Tyrosine derivatives:- Catecolamines (epinephrine, dopamine)- Thyroid hormones

• Tryptophan derivative:- Melatonin

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Amino acid derivatives

HORMONE SOURCE

1 Acetylcholine Otonomic nerve

2 Tyroxine Tyroid

3 Tryodotyronine Tyroid

4 Epinephrine Adrenal medulla

5 Norepinephrine Adrenal medulla

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Steroid

• Derived from cholesterol

• 2 groups:

- with the intact steroid ring (adrenal and gonadal steroid)

- with the steroid ring cleaved (metabolites of vit D)

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Steroid

HORMONE SOURCE

1 Aldosteron Adrenal cortex

2 Glucocorticoid Adrenal cortex

3 Testosteron Testis

4 Estrogen Ovarium

5 Progesteron Luteum corpus

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Klasifikasi Hormon

Grup I Grup II

Tipe Steroid, tiroksin Polipeptida, amin

solubilitas lipofilik hidrofilik

Protein pengangkut ada tidak ada

Usia paruh plasma panjang pendek

Resptor intraseluler membran plasma

Mediator Kompleks reseptor hormon

cAMP, cGMP, Ca2+, protein kinase

PEPTIDE AND PROTEIN HORMONES

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Hormon peptida terkecil tiroliberin (3 asam amino) terberat tirotropin (BM 20.000)

Batas hormon peptida dg protein hormon berdasarkan BM relatif kira2 10.000.

Peptide/protein hormones bersifat larut dalam air (hidrofilik)

Biasanya disimpan dalam sel kelenjar dan disekresikan secara terkontrol

Peptide & Protein Hormones

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Peptide/protein hormone synthesis

AMINE HORMONES

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Amine hormones

Ada dua kelompok hormon derivat asam amino tirosin

Thyroid hormones and Catecholamines

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Thyroid hormones

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Synthesis of Thyroid Hormone

Biosintesis Hormon Tiroid1. Uptake ion iodida oleh kelenjar tiroid - penyerapan secara transpor aktif - uptake dipengaruhi hormon TSH - dihambat oleh: tiosianat, perklorat, garam

iodida

2. Oksidasi iodida dan iodinasi gugus tirosil tiroglobulin

- iodida dioksidasi oleh enzim peroksidase reaksi ini dihambat oleh tiourea, aminobenzen

- yodium yg terbentuk diikatkan pada gugus tirosil tiroglobulin membentuk MIT dan

DIT

Biosintesis Hormon Tiroid

3. Perubahan radikal tirosil menjadi radikal iodotironil

- terjadi penggabungan 2 mol DIT membentuk tetraiodotironin (T4) dan penggabungan DIT dg MIT membentuk triiotironin (T3)

- distribusi yodium dlm kelenjar tiroid: MIT 20-30%, DIT 30-45%, T3 5-8%, T4 25%

4. Pelepasan T3 dan T4 ke dalam darah - dlm plasma T3 dan T4 berikatan dg protein yg td:

thyroxin binding globulin, thyroxin binding prealbumin, albumin - 0,05% tidak terikat protein hormon yang aktif

Thyroid Hormone Degredation

Catecholamine hormones

Catecholamines merupakan neurohormon dan neurotransmitter

Terdiri dari epinephrine, and norepinephrine

Epinephrine and norepinephrine dihasilkan medulla adrenal dan bersifat larut dalam air

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Synthesis of catecholamines

Amine Hormones

Asam amino lain yang digunakan untuk sintesis hormon adalah:

• Tryptophan merupakan prekursor serotonin dan melatonin

• Histidin untuk membentuk histamine

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STEROID HORMONES

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Semua hormon steroid merupakan derivat dari kolesterol dan berbeda hanya pada struktur cincin dan rantai sampaing nya

Semua hormon steroid larut dalam lemak

Steroid hormones

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Macam2 hormon Steroid

• Glucocorticoids; ex cortisol

• Mineralocorticoids; ex aldosterone

• Androgens spt testosterone

• Estrogens, termasuk estradiol and estrone

• Progestogens (dikenal sebagai progestins) seperti progesterone

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Hormones Steroid• Tidak disimpan, segera disekresikan setelah

disintesis

• Enzymes yang menghasikan hormon steroid terletak di mitokondria dan smooth ER

• Pada saat ditransport dalam darah, hormon terikat protein spesifik (spesifik binding protein)

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Steroids can be transformed to active steroid in target cell

Sintesis Hormon Steroid

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cholesterol

Extracellularlipoprotein

Cholesterolpool

LH

ATP

cAMPPKA+

Pregnenolone

Progesterone

Androstenedione

TESTOSTERONE

3HSD

P450c17

17HSD

acetate

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Katabolisme Hormon Steroid• Terjadi terutama di hati

• Proses inaktivasi td:

- reaksi reduksi, pada gugus keto dan ikatan rangkap cincin A

- Pembentukan konjugat melalui reaksi esterisasi da as sulfat atau glikosilasi dg as glukuronat shg membentuk metabolit

• Mamalia tdk dapat memecah kerangka dasar steroid

EICOSANOIDS

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Eikosanoid

• Eikosanoid berasal dari asam arakidonat (as lemak 20 atom C dg 4 ikatan rangkap)

• Contoh terpenting kelompok ini adalah prostaglandins, prostacyclins, leukotrienes and thromboxanes.

Eikosanoid

• Pembentukan eikosanoid dimulai dalam membran plasma dg cara melepaskan arakidonat dari fosfolipid oleh fosfolipase A2

• Kerja kortikosteroid berperan pada metabolisme eikosanoid

• Kortikosteroid menginduksi protein lipokortin yang menghambat fosfolipase A2 menghambat inflamasi

MEKANISME KERJA

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Mekanisme Kerja Hormon Lipofilik

• Tempat kerja di dalam inti sel• Hormon berikatan dengan reseptor yang

terletak di dalam sel.• Kompleks hormon reseptor merupakan sinyal

intra sel yang akan mempengaruhi transkripsi gen

• Satu hormon yang sama dapat menghasilkan respon yang berbeda pada berbagai jaringan

Mekanisme Kerja Hormon Hidrofilik

• Hormon hidrofilik tidak mampu menembus membran sel

• Sinyal diteruskan ke bagian dalam sel oleh reseptor yang berada pada membran (transduksi sinyal) dengan melepaskan second messenger seperti cAMP, cGMP, Ca2+, fosfatidilinositol, arakidonat

Mekanisme Kerja Hormon Hidrofilik

• Ada tiga jenis reseptor

1. Reseptor jenis I

- memiliki aktivitas seperti enzim

- reseptor berupa tirosin-kinase

- contoh: insulin dan growth hormon• 2. Reseptor jenis II

- merupakan kanal ion

- sel bereaksi thd perubahan kadar ion

- contoh neurotransmitter

Mekanisme Kerja Hormon Hidrofilik

3. Reseptor jenis III

- pemindahan sinyal dg bantuan protein G

- digunakan pada banyak hormon hidrofilik

PENGATURAN

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Nervous system

•The nervous system exerts point-to-point control through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast.

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Hormones travel via the bloodstream to target cells

•The endocrine system broadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular fluid.

•Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.

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Principal functions of the endocrine system

• Maintenance of the internal environment in the body (maintaining the optimum biochemical environment).

• Integration and regulation of growth and development.

• Control, maintenance and instigation of sexual reproduction, including gametogenesis, coitus, fertilization, fetal growth and development and nourishment of the newborn.

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Sensing and signaling

Endocrine “glands” synthesize and store hormones. These glands have a sensing and signaling system which regulate the duration and magnitude of hormone release via feedback from the target cell.

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Regulation of hormone secretion

Sensing and signaling: a biological need is sensed, the endocrine system sends out a signal to a target cell whose action addresses the biological need.

Key features of this stimulus response system are:        receipt of stimulus

        synthesis and secretion of hormone

        delivery of hormone to target cell

        evoking target cell response

        degradation of hormone

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Major hormones and systems• Top down organization of endocrine system.

• Hypothalamus produces releasing factors that stimulate production of anterior pituitary hormone which act on peripheral endocrine gland to stimulate release of third hormone– Specific examples to follow

• Posterior pituitary hormones are synthesized in neuronal cell bodies in the hypothalamus and are released via synapses in posterior pituitary. – Oxytocin and antidiuretic hormone (ADH)

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Control of Endocrine Activity

• The physiologic effects of hormones depend largely on their concentration in blood and extracellular fluid.

• The concentration of hormone as seen by target cells is determined by three factors:

Rate of productionRate of deliveryRate of degradation and elimination

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Control of Endocrine Activity

Rate of production: Synthesis and secretion of hormones are the most highly regulated aspect of endocrine control. Such control is mediated by positive and negative feedback circuits, as described below in more detail.

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Feedback control

• Negative feedback is most common: for example, LH from pituitary stimulates the testis to produce testosterone which in turn feeds back and inhibits LH secretion

• Positive feedback is less common: examples include LH stimulation of estrogen which stimulates LH surge at ovulation

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Feedback control of insulin by glucose concentrations

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Feedback Control of Hormone Production

Feedback loops are used extensively to regulate secretion of hormones in the hypothalamic-pituitary axis. An important example of a negative feedback loop is seen in control of thyroid hormone secretion

Negative feedback effects of cortisol

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Control of Thyroid Hormone Synthesis and Secretion

Control of Endocrine Activity

Rate of delivery: An example of this effect is blood flow to a target organ or group of target cells - high blood flow delivers more hormone than low blood flow.

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Control of Endocrine ActivityRate of degradation and elimination: Hormones, like all biomolecules, have characteristic rates of decay, and are metabolized and excreted from the body through several routes. Shutting off secretion of a hormone that has a very short half-life causes circulating hormone concentration to plummet, but if a hormone's biological half-life is long, effective concentrations persist for some time after secretion ceases.

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Neural control

• Neural input to hypothalamus stimulates synthesis and secretion of releasing factors which stimulate pituitary hormone production and release

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THAK YOUTERIMA KASIH

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