Biokimia Hormon

Blok 1.2
 Hormon
• Hormon: senyawa kimia yang disekresikan
oleh specific glands atau cell dan
berperan sebagai chemical messenger
atau signal molecule
• Kontrol segala aktifitas sel melalui
sinyal.
• Hormon dalam sirkulasi darah sangat
rendah (10–12 - 10–7 mol L–1).
 Fungsi Hormon

Growth & Development

Reproduction

Hormones

Maintenance of Energy production,

internal environment utilization & storage
Cell Communication

GAS MOLECULE
Generalized Signal Transduction Pathway
Simple Intracellular & Extracelluler
Signaling
The hierarchical control of hormone release
 Receptor
Receptor: specific membrane protein, dapat
mengenal dan berikatan dengan
corresponding ligand molecules, aktiv, dan
transduce signal ke next signaling
molecules:
A. Membran
B. Intra Sel
Glycoprotein atau Lipoprotein
 Receptor types
• Ion-channel-linked receptors ( neuro
transmitres)
• G-protein-linked receptors
• Enzyme-linked receptors
 Receptor typ.......

There are five basic types of membrane bound

receptors (grouped by signal transduction method):
1. tyrosine kinase receptors
2. receptors that are closely linked to tyrosine kinases
3. receptors with guanylyl cyclase activity
4. receptors that serve as transporters
5. G protein-coupled receptors
 G- Protein Receptor
Signal-binding site

Segment that
interacts with
G proteins

G-protein-linked receptor
1. G Protein-coupled receptors
• receptors : coupled with guanine
nucleotide-binding proteins (G proteins)
• activate various signaling pathways :
– Receptors for LH, FSH, TSH, GnRH,
dopamine, serotonin, glutamine, parathyroid
hormone, interleukins, etc.
 Struktur G- Protein
• 7-transmembrane segment receptors
– extracellular site for hormone (ligand)
– intracellular site for GTP-binding protein
• Two kinds: "heterotrimeric G proteins" and "small G proteins
• triggers dissociation of GDP and binding of GTP to -subunit
of G protein
• G-GTP complex dissociates from G and migrates to
effector sites, activating or inhibiting
• But it is now clear that G also functions as a signalling
device
 G- Protein ...

7 transmembrane domains
3 intracellular loops
3 extracellular loops
G Protein-Coupled Receptor Superfamily

-NH2

COOH-
G Protein-Coupled Receptor Superfamily

• Common functional features:

- binding to the receptor activates a G protein
- each receptor is associated with a specific type of
G protein
- each G protein type has different functions:
- Gs: stimulates cyclic AMP
- Gi: inhibits cyclic AMP
- Go activates phospholipase C
Heterotrimeric G-protein α-subunit subfamilies
and their effects
Tyrosine kinase
 A. attach phosphates to tyrosines
• H-R : induce phosphorylating activity of the
receptor
• A receptor tyrosine kinase can trigger multiple
signal transduction pathways at once
• kinase : phosphotransferase (enzyme) that
transfers phosphate groups from high-energy
donor molecules, such as ATP, to specific
substrates. The process is referred to as
phosphorylation.
Example: Insulin receptor

extracellular domains
(ligand binding)

plasma membrane

tyrosine phosphorylase phosphorylated enzyme (altered

domains activity)
Signal Signal-binding site
molecule
 Helix in the Signal
membrane molecule

Tyr Tyr
Tyrosines Tyr Tyr Tyr Tyr
Tyr Tyr
Tyr Tyr Tyr Tyr
Tyr Tyr
Tyr Tyr Tyr Tyr

Receptor tyrosine
kinase proteins Dimer
CYTOPLASM (inactive monomers)

Activated relay
proteins

Cellular
Tyr Tyr P Tyr Tyr P P Tyr Tyr P response 1
Tyr Tyr P Tyr Tyr P Tyr Tyr P
P
Tyr Tyr P Tyr Tyr P P Tyr Tyr P Cellular
6 ATP 6 ADP response 2

Activated tyrosine- Fully activated receptor

kinase regions tyrosine-kinase
(unphosphorylated (phosphorylated Inactive
dimer) dimer) relay proteins
 B. Closely linked to tyrosine kinases

Receptors : closely linked to tyrosine kinases. These

activate cytoplasmic tyrosine kinase enzymes.

Growth Hormone Receptor

associated
tyrosine
kinase

phosphorylated enzyme
 C. Guanylyl Cyclase Activity
3) Receptors with. Binding to the receptor activates
guanylate cyclase region of the receptor, causing
conversion of GTP to cyclic GMP.
Example: Atrial Natriuretic Peptide Receptor

guanylate
GTP cyclase
ion channels
cyclic GMP protein kinase G
phosphodiesterase levels
 D. Transporter
Receptors that serve as transporters. These move
the ligand inside the cell, where they have an
effect. (Not typical for hormones).
Example: Iron, transported by transferrin receptor

iron

transferrin
 Intracellular receptors

1. The glucocorticoid receptor protein: contains a

number of different functional domains
DNA-binding domain, in the cytosol
complexed with a variety of proteins heat shock proteins
binds to specific DNA-responsive elements and activates gene
transcription.
2. Retinoid X receptor (RXR) and orphan receptors are
not accompanied by chaperone proteins.
1. Hormone (-) : bind to their specific DNA sequence, repressing the
gene.
2. Hormone (+) : activate the transcription of the gene that they were
repressing.
3. NOD-like receptors : recognition receptors group,
regulation of inflammatory and apoptotic processes.
intracellular signalling
 Hormon - Receptor

• highly specificity
• highly affinity
• saturation
• reversible binding
• special function model
 Pengaturan receptor

• Phosphorylation atau
dephosphorylation dari Receptor
• Phospholipid membran
• Enzyme catalyzed hydrolysis
G protein
 Fungsi receptor

(1) Recognize the special ligand

(2) Binding to special ligand
(3) Signal transduction
biological effect
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
 Releasing Hypothalamus Nervous
hormones
Anterior pituitary
Posterior pituitary
Thyrotropin
Somatotropin FSH Vasopressin
LH Prolactin Oxytocin
ACTH

Adrenal Adrenal
Thyroid Cortex Pancreas Ovary Testis Medulla

T3 Cortisol Insulin, Estradiol Testosterone Epinephrine

aldosterone glucagon,
somatostatin

Muscles Liver, Reproductive Mammary

liver Tissues muscles organs glands
 Struktur Kimia Hormon
1. Derived from amino acids (Hydrophilic)
Amino acid derivatives thyroxine
Histamine, serotonin, melatonin, and the
catecholamines, dopa, dopamine,
norepinephrine, and epinephrine are
known as “biogenic amines.”
Tripeptides TRH
Small peptides VP (ADH), somatostatin
Intermediate-size insulin, parathyroid hormone
peptides
Complex polypeptides gonadotropins, TSH
and glycoproteins
A. Signaling substances derived from amino acids
B. peptide hormones dan proteohormones
 2. lipid precursor
Cholesterol derivatives cortisol, testosterone, vitamin D ,
estradiol
Fatty acid derivatives prostaglandins, leukotrienes
Phospholipid derivative platelet-activating factor
Cholesterol derivatives
Lipophilic hormones
Steroid hormones
 3. Derived from other chemicals (mediator)
Purines adenosine
Gases nitric oxide
Hormon Pituitary - hypothalamic
Klasifikasi: Mekanisme Kerja
• Hormones : bind to cell surface
receptors
– Most signalling molecules cannot pass through the
cell membrane
– Receptors: in the cell membrane
• Hormones : bind to nucleus
– Small hydrophobic signal molecules can diffuse
directly into the cell cytoplasm
– Their receptors are cytoplasmic or nuclear
Hormon: cell surface receptors
• Secon Messenger
– cAMP
– cGMP
• calcium atau phosphatidylinositols (or both)
• kinase atau phosphatase cascade
 Hormones : cell surface receptors

A. The second messenger is B. The second messenger is

cAMP: adenylyl cyclase cGMP:
phosphodiesterase
• α2-Adrenergic catecholamines • Atrial natriuretic factor
• β-Adrenergic catecholamines • Nitric oxide
• Adrenocorticotropic hormone
• Antidiuretic hormone
• Calcitonin
• Chorionic gonadotropin, human
• Corticotropin-releasing hormone
• Follicle-stimulating hormone
• Glucagon
• Lipotropin
• Luteinizing hormone
• Melanocyte-stimulating hormone
• Parathyroid hormone
• Somatostatin
• Thyroid-stimulating hormone
 Hormones …..

C. The second messenger is calcium or D. The second messenger is a kinase

phosphatidylinositols (or both): or phosphatase cascade:

• Acetylcholine (muscarinic)
• α1-Adrenergic catecholamines • Chorionic somatomammotropin
• Angiotensin II • Epidermal growth factor
• Antidiuretic hormone • Erythropoietin
(vasopressin) • Fibroblast growth factor
• Cholecystokinin • Growth hormone
• Gastrin • Insulin
• Gonadotropin-releasing • Insulin-like growth factors I and II
hormone • Nerve growth factor
• Oxytocin • Platelet-derived growth factor
• Platelet-derived growth factor • Prolactin
• Substance P
• Thyrotropin-releasing hormone
 Second messengers
• signalling molecules that are rapidly
generated/released and can then go on to
activate effector proteins within the cell to exert
a cellular response.
– Hydrophobic :
• Diacylglycerol
• inositol triphosphate (IP3)
• phosphatidylinositols
– Hydrophilic: cAMP, cGMP and calcium,located within the
cytosol.
– Gases: nitric oxide and carbon monoxide, diffuse both through
the cytosol and across cellular membranes.
 Second messengers
I. Cyclic nucleotides (cAMP, cGMP)
II. Lipid products (DAG, phosphoinositol
lipids)
III. Ions, small molecules(Ca2+, NO, Na+, K+)
IV. Modified proteins (phosphorylation,
modular (domains)
 2. Hormones : intracellular receptors

• Androgens
• Calcitriol (1,25[OH]2-D3)
• Estrogens
• Glucocorticoids
• Mineralocorticoids
• Progestins
• Retinoic acid
• Thyroid hormones (T3 and T4)
 Hormon – second Massengger
• Hormone : first messenger
• Second messenger : - Ca2+, cAMP or
other, released when the hormone binds
to its (extracellular) receptor
• Second messenger then activates /
inhibits processes in the cytoplasm or
nucleus
• Degradation and/or clearance of the
second messenger is also (obviously)
important
 G proteins:stimulate or inhibit an effector

• adenylyl cyclase
• stimulatory G protein : Gs
• inhibitory G protein : Gi
• Gi :
• Gi subunit binding to AC
• Gi -Gi preventing it from binding to AC
• cholera toxin and pertussis toxin
 Referensi
• MURRAY, R. K., BENDER, D. A., BOTHAM, K. M., J, P., KENNELLY,
RODWELL, V. W. & WEIL, P. A. (2009) Harper’s Illustrated Biochemistry,
The McGraw-Hill Companies, Inc
• VOET, D., G.VOET, J. & PRATT, C. W. (2008) FUNDAMENTALS OF
Biochemistry :LIFE AT THE MOLECULAR LEVEL, John Wiley & Sons, Inc.
• KOOLMAN, J. & ROEHM, K.-H. (2005) Color Atlas of Biochemistry, New
York, Thieme.
• JAIN, J. L., JAIN, S. & JAIN, N. (2005) FUNDAMENTALS OF
BIOCHEMISTRY, NEW DELHI, S. CHAND & COMPANY LTD.
• Fry Mitchell, 2010 Essential biochemistry for medicine, Oxford, John Wiley
& Sons Ltd
• Michal Gerhard and Dietmar Schomburg (ed), 2012, Biochemical Pathways:
An Atlas of Biochemistry and Molecular Biology, Second Edition, John Wiley
& Sons, Inc.
1. Identify differences between autocrine, paracrine, and
• endocrine signaling

• 2. Distinguish major differences between insulin and

• glucagon signaling, and differences in how receptors
• are activated (ie, RTK versus GPCR)

• 3. Understand RTK signal transduction mechanisms

• 4. Relationship between RTK activation and gene expression