bahan ajar dr. Susila Sastri M.Biomed.
Mekanisme
Kerja
Hormon
Blok 1.4
(2)
Hormone Action
• Efek primer pada sel ( ikatan hormon – reseptor spesifik): hormone–receptor complex
• H-R complex → effector system → signal
transducing mechanism → biochemical
(3)
(4)
(5)
(6)
(7)
The DNA sequences of several
(8)
Hormon:
Transmembrane Receptors– Enzyme coupled receptors: Signal activates an enzyme activity of the receptor itself—
tyrosine kinases, phospholipase C.
– G-protein coupled receptors: Signal activates a G-protein that activates
downstream enzymes—makes second messenger(cAMP or Ca2).
– Ion-channel coupled receptors: Signal activates an ion channel
(9)
Effector systems
•
Hormone–receptor complex:
meningkatkan
aktivitas
– enzim
– G-protein
–
ion channel
(10)
Hormone–receptor complex: meningkatkan aktivitas enzim protein kinase
(11)
PROTEIN KINASES
1. Transmembrane receptor kinases : tyrosine kinase
ATP : phosphorylate specific tyrosine enzymatic (amplification step).
2. serine/ threonine protein kinases
ATP to phosphorylate specific serine or threonine.
• phosphorylation cascades :
one kinase phosphorylates another → MAP kinase kinase kinase. (mitogen-activated protein
kinase that phosphorylates MAP kinase kinase)
(12)
(13)
(14)
Hormon:
Membrane-bound phospholipase• Hydrolisa: phosphatidylinositol bisphosphate (PIP2)
→ dua messenger ,
– inositol trisphosphate (IP3) – diacylglycerol (DAG)
• example: adrenaline binding to the α-receptor in the liver: Ca2+ ions stimulate glycogenolysis
(15)
(16)
(17)
Pengaturan Enzym & protein:
calcium atau calmodulin.
• Adenylyl cyclase
• Ca2+-dependent protein kinases
• Ca2+-Mg2+ ATPase
• Ca2+-phospholipid-dependent protein kinase • Cyclic nucleotide phosphodiesterase
• Some cytoskeletal proteins
• Some ion channels (eg, L-type calcium channels) • Nitric oxide synthase
• Phosphorylase kinase
• Phosphoprotein phosphatase 2B
(18)
Gomplex activates G-protein
• H-R complex: activates G-protein →activates a membrane-bound enzyme
(e.g. adenyl cyclase, which converts ATP to cyclic AMP).
(19)
(20)
Pathway of glycogenesis and of glycogenolysis in the liver
(21)
(22)
(23)
(24)
(25)
Cyclic GMP
• Cyclic GMP: berasal dari GTP dengan
bantuan enzym guanylyl cyclase (activate : atrial natriuretic factor)
(26)
(27)
(28)
(29)
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.
(30)
Energi
Kontraksi
Otot
Blok 1.3
(31)
Protein
Otot
Rangka
• Myosin • Actin
– Troponin C
– Troponin I
(32)
(33)
(34)
ATP
(adenosine
triphosphate)
•
Energi
kontraksi
otot
•
Pompa
Calcium
ke
sarcoplasmic
reticulum
pada
saat
relaksasi
•
Mempertahankan
membran
potensial
(sodium/potassium
ion
gradients
(35)
(36)
Sintesis
ATP
pada
Metabolisme
Aerob
•
Phosphocreatine.
•
Glycolysis
dari
Glycogen
atau
Glucosa.
•
Tricarboxylic
acid
cycle
(TCA
or
Krebs
cycle).
(37)
(38)
Metabolisme
Otot
Rangka
I
•
Kontraksi
otot
membutuhkan
ATP
yang
banyak
•
Bila
tidak
terjadi
resintesis
ATP
maka
sumber
ATP
yang
ada
hanya
dapat
berkontraksi
1
detik.
•
Creatine
phosphate
berperan
sebagai
buffer
(39)
A. Energy metabolism in muscle fibers
• Red fibers (type I fibers): prolonged effort. Energi berasal dari metabolisme aerobic
tergantung pada suplay O2.
• White fibers (type II fibers: fast, strong contractions.
(40)
(41)
•
Red
fiber
ATP
:
– fatty acids: β‐oxidation – tricarboxylic acid cycle – respiratory chain
•
The
red
color
:
monomeric
heme
protein
myoglobin,
O2
cadangan
•
Myoglobin:
affinitas
terhadap
O2
tinggi
dari
hemoglobin
dan
melepaskan
O2
bila
tekanan
parsial
O2
kurang
(42)
Anaerob
Piruvat As. Laktat (Otot)
Hepar As. Laktat Piruvat Laktat dehidrogenase Siklus Cory otot TCA
(43)
Glycogen
Otot
Rangka
•
sarcoplasm
kaya
glycogen,
pada
granule
dekat
I band
.
•
Pembebasan
glucosa
glycogen
(glikogenolisis
diatur
oleh
muscle
glycogen
phosphorylase
,
melalui
Ca2+, epinephrine,
and AMP.
•
Ca2+
:
memulai
muscle
contraction
dan
mengaktifkan
proses
pembentukan
energi
melalui
metabolisme
(44)
Penyakit
Gangguan
Glikogenolisis
•
McArdle
disease:
glycogen
storage
diseases:
Muscle glycogen
(45)
Phosphocreatine
(
creatine
phosphate
/
Pcr)
•
Cadangan
energi
otot
•
Creatine
:
sintesis
pada
liver
(Arg,
Gly,
Met),
dibawa
ke
sel
otot,
posporilasi
oleh
creatine
kinase
menjadi
creatine
phosphate.
(46)
(47)
Sintesis
Creatine
• Step I : kidneys dan Step II: liver
• Kidney: gugusan guanidino arginine ditransfer ke glycine membentuk guanidino acetate
• Liver: N‐methylation dari guanidino acetate terbentuk creatine .
(48)
Sumber
ATP
pada
Olah
ragawan
•
Sprinter:
Creatine
Phosphate
&
Anaerobic
Glycolysis
:
sumber
ATP.
–
100
‐
m
sprint
:
creatine
phosphate
(first
4–5
seconds)
dilanjutkan
anaerobic
glycolysis,
melalui
glycogen
otot
(49)
Sumber
ATP..
•
Marathon
Runner
:
Oxidative Phosphorylation–
Sumber
utama
glukosa
:
• blood glucose
• free fatty acids, lipolisis (triacylglycerols
(50)
Smooth
muscle
• Smooth muscles: blood vessel walls dan walls
of the intestines tidak seperti serat otot rangka
• spindle‐shaped, contractile proteins less regular pattern dari striated muscle.
(51)
Smooth..
• Ca2+ (Ca2+‐calmodulin) mengaktifkankontraksi smooth muscle; tidak melalui troponin tetapi melalui troponin, tetapi
protein kinase sehingga mengaktifkan myosin’s ATPase activity.
• Hormones such as epinephrine dan
angiotensin II dapat mempengaruhi vascular
(52)
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
• KOOLMAN, J. & ROEHM, K.‐H. (2005) Color Atlas of Biochemistry, New York, Thieme.
(53)
Pengantar
Blok
1.5
UROGENITAL
Blok 1.5 Koordinator
(54)
TUJUAN
BLOK
•
Mahasiswa
mampu
menjelaskan
struktur
dan
fungsi
sistem
urogenital,
keseimbangan
asam
basa
dan
elektrolit,
peranannya
dalam
homeostasis
serta
korelasi
klinisnya
(55)
AREA
KOMPETENSI
• Komunikasi efektif
• Landasan ilmiah ilmu kedokteran
• Pengelolaan informasi
• Mawas diri dan pengembangan diri
• Etika, Moral, Medikolegal dan
professionalisme serta keselamatan pasien
(56)
BAGIAN
TERINTEGRASI
• Anatomi • Biologi • Histologi • Biokimia • Fisiologi • IPD
• IKA • PK
• Obgyn
(57)
Kidney
Anatomy
(58)
Kidney
Histology
(59)
Kidney Physiology: Mechanisms of Urine Formation
(60)
Biokimia
&
Kelainan
Urine
• Komposisi dan kelainan
• BJ, pH
• Sendimen urin
(61)
Ureters
(62)
Urinary
Bladder
(63)
Micturition
(64)
Electrolyte,
and
Acid
‐
Base
Balance
(65)
The
Reproductive
System
• Wanita
• Laki‐laki
• Kelainan kongenital]
• Kelainan Klinis
(66)
(67)
(68)
(69)
REFERENSI
• Atlas anatomi
• Anatomi Snell
• Atlas Histologi
• Biokimia Harper
• Fisiologi Guyton, Ganonng, Tortora
• Etc?
(70)
TUTORIAL
• SKENARIO 1 :
• SKENARIO 2 :
• SKENARIO 3 :
• SKENARIO 4 :
• SKENARIO 5 :
• SKENARIO 6 :
(71)
Skills
Lab
(72)
Praktikum
• Anatomi
• Histology
• Biokimia
• Biology
• Clinical phtology
(73)
Evaluasi
• Tutorial
• Skills lab
• Ujian akhir Blok
(74)
Biokimia
Hormon
Blok 1.4
(75)
Hormon
• Hormon: senyawa kimia yang disekresikan
oleh specific glands atau cell dan
berperan sebagai chemical messenger
atau signal molecule
• Hormon dalam sirkulasi darah sangat
(76)
(77)
Hormones Reproduction
Reproduction Growth &Growth & DevelopmentDevelopment
Maintenance of
internal environment
Energy production,
Energy production,
utilization & storage
utilization & storage
Fungsi Hormon
(78)
(79)
GAS MOLECULE
(80)
(81)
(82)
(83)
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
(84)
Hormon
-
Receptor
•
highly specificity
•
highly affinity
•
saturation
•
reversible binding
(85)
Pengaturan
receptor
• Phosphorylation atau
dephosphorylation dari Receptor
• Phospholipid membran
• Enzyme catalyzed hydrolysis
(86)
(1) Recognize the special ligand
(2) Binding to special ligand
(3) Signal transduction
biological effect
(87)
(88)
Hypothalamus Anterior pituitary Posterior pituitary Thyrotropin ACTH Somatotropin LH FSH Prolactin Vasopressin Oxytocin Thyroid Adrenal Cortex Adrenal Medulla Pancreas Ovary Testis
Muscles liver Tissues Liver, muscles Estradiol Testosterone Insulin, glucagon, somatostatin T3 Cortisol aldosterone Mammary glands Reproductive organs Epinephrine Releasing hormones Nervous
(89)
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 peptides
insulin, parathyroid hormone Complex polypeptides
and glycoproteins
(90)
(91)
(92)
2. lipid precursors
Cholesterol derivatives cortisol, testosterone, vitamin D ,
estradiol
Fatty acid derivatives prostaglandins, leukotrienes
(93)
(94)
(95)
(96)
(97)
(98)
3. Derived from other chemicals (mediator)
Purines adenosine
(99)
(100)
(1)
(2)
Complex IV
•
acceptor ion H adalah
O2
•
Cytochrome
c
oxidase
•
4 redok
center : cytochrome
a
, cytochrome
a
3,
CuB
dan
CuA
•
Ion H
intermembrane space
masuk
ke
matrix :
(3)
(4)
Inhibitor ETC
•
Complex I : Rotenon, Amytal
dan
Piericidin
A
•
Complex III : Actimicyn
A
•
Complex IV: Cyanida, Carbon monoxide
–
ion Cyanide berkompetisi
dengan
O2 untuk
berikatan
dengan
cytochrome c oxidase
pada
oxygen-binding
site.
–
ATP
synthase
:
Oligomycin
(5)
Pembentukan
ATP
•
2 electron (NADH) melewati
Complex I, III,
IV menghasilkan
10 proton (H+) pada
intermembran space: enghasilkan
3 ATP
•
2 electron FADH2 melewati
complex
II,III,IV menghasilkan
6 proton pada
intermembrane space :
2 ATP
•
Energi
bebas
yang dibutuhkan
untuk
sintesis
satu
ATP: 40-50 kJ/mol
(6)
Referensi
• C.TOY, E., WILLIAM E. SEIFERT, J., STROBEL, H. W. & HARMS, K. P. (2008 ) Case Files™ Biochemistry.
• 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.