BIOMEDIC 2 MUSCULOSCELETAL SYSTEM

BIOCHEMISTRY OF BONE &

MUSCLE

dr. Syahrijuita, M.Kes, Sp.THT-KL

BIOCHEMISTRY DEPARTMENT
Faculty of Medicine Hasanuddin University
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2011
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Biochemistry of Bone
Sub topic:

Calsium Metabolism
Biochemistry of Bone
Biochemistry of Cartilage
Sinthesis of Uric Acid

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Learning Objectives

Describe the Calsium Metabolism

Describe the chemical composition of the
bone and process of mineralization
Describe the chemical composition of the
cartilage
Describe sinthesis of the uric acid
Describe the phatology of genetic diseases
from errors of the bone and cartilage ,Calsium
metabolism and hiperurikemia
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Regulation of Calcium Homeostasis
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 COMPARISON OF TWO TYPES OF DENSE
CONNECTIVE TISSUE BONE & CARTILAGE

Characteristics Cartilage Bone

Mechanical properties Rigid but flexible Hard and strong

Cell type Chondrocytes Osteocytes

Composition of Matrix Chondroitin sulfate Hydroxyapatite

Vascularization Avascular Vascular

Innervation No Yes

Covering Perichondrium Periosteum

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 Bone

Bone: Type I collagen and

hidroksiapatit
cartilago: Type II collagen and
Proteoglicans

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The Principal proteins found in bone

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 4 % compact bone remodeling every year
and 20% trabecular bone exchange
Process bone remodelling :
Resorption osteoclast
Formationosteoblast
Bone serves as store of Calsium

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The Difference Between Osteoclast
and Osteoblast

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Influencing Factors of
oteoclast/osteoblast

Activator of ostoeblast:
PTH
1,25 dihidroksicole calciferol
T3; T4
hGH : IGF - 1
PGE2
TGF
Estrogen

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Inhibitor of Osteoblast : Kortikosteroid
Activator of osteoclast :
PTH
1,25 dihidroksicole calciferol
IL-1 ; IL-6
TNF
TGF
Inhibitor of Osteoclast
Calcitonin
Estrogen
TGF
INF
PGE2

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Phatology of Genetic
Metabolism at Bone and Cartilage
Diseases :
Osteogenesis Imperfecta : Sklera tipis, tembus,
biru Mutasi gen Col1A1 & Col1A2 sintesa &
struktur kolagen I
Osteoporosis : bone mass per unit volume
decrese
pasca menopause (>>)
Mutasi gen Col1A1 dan Col1A2 (<<)
Osteoarthritis : CS KS & HA , mutasi gen
Col2A1 (<<)
Achondroplasia tanatoforik : mutasi gen code
FGFR 3
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Sinthesis Uric Acid

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BIOMEIC 2 MUSCULOSCELETAL SYSTEM

BIOCHEMISTRY OF MUSCLE

dr. Syahrijuita, M.Kes,Sp. THT-KL

BIOCHEMISTRY DEPARTMENT
FACULTY OF MEDICINE HASANUDDIN UNIVERSITY
2011

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SUB TOPIC:
Synthesis dan Hydrolysis Ach at NMJ
Muscle Proteins
Muscle Energy Metabolism

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Learning Objectives
Describe structure, synthetis and
hydrolysis of Ach at NMJ
Describe muscle proteins
Describe muscle energy metabolism

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 Stucture , Synthesis dan Hydrolysis
Acetylcholin at Neuro Muskular
Junction
Neuro Muskular Junction or motor end-
plate: location of connected neurons and
muscles
Asetilkolin (Ach) chemical structure :
(CH3)3-N+-CH2- C2H2- O-C- CH3
O
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ACETYLCHOLIN :

The first Neuroransmitter isolated

Synthesis at terminal presinaps
neuron colinergic
Storage in vescile
Secretion by exositosis

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Stage of Synthesis and Hydrolysis Ach
at NMJ
1. Synthesis Ach in sitosol neuron terminal:
Cholinacetyltransferase
Acetyl-CoA + Cholin Acetylcholin + CoA
2. Ach storage in synaptic vesiclles
3. Sexcretion of Ach from vesicles to sinaps cleft
and exositosis results miniatur potensial end
plate (depolarisation)
causing voltage gated Ca2+ channels to open

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4. Ach binding receptor forward passed
membran .
Na+ influks K+ exfluks depolarisasi
potensial action + muscle contraction
5. Ach hydrolis after receptor channels closed:
acetylcholinesterase
Ach + H2O Acetat + Cholin
6 Cholin recycles to terminal neuron to
resynthesis Ach

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Clinical Manifestation : miastenia gravis = antibodi attac
Ach receptor
At NMJ : Forming autoantibodi Ach receptor

Receptor damage (lysis local) by autoantibodi

results crossbinding and endositosis

Decrese of receptor clearly

Symptoms : episodic musles weakness which
innervasion by cranial neurons.

R/: Cholinesterase Inhibitor

To increase total Ach at NMJ

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Muscle Proteins
Muscle: Biochemistry mechine influens
chemical energy to mecanical/kinetic energy
Three (3) Type of muscle :
Skeletal volunter
Cardiac striated
Smooth non striated involunter
Sarcomere is the functional contractile unit
Muscle contraction : the thick and thin filaments

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Muscle Proteins
Striated muscle : Miosin, Aktin, tropomiosin,
troponin I, T, C, (3 major proteins )
Smooth muscle : without Troponin

Kalmodulin

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Actin :
BM 45.000 Dalton
Initial synthesis as actin globular
After binding ATP dan mol Ca2+
formed Aktin F
Double helix supercoil

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Minor Proteins
Tropomyosin :
molekular fibrosa
2 and chains
binding at helix actin F
Troponin :
3 polypeptids
Tipe T : binding with tropomiosin
Tipe I : avoid interaction myosin actin
Tipe C : Binding Ca2+ to start contraction
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Myosin ~ Myosin II
Major Protein at muscle 55 %
BM : 460.000 Dalton
Ta.: 3 pairs protein, 1 pairs long chains
200.000 Dalton, 2 pairs short chains
20.000 Dalton
Secunder Structure heliks with residu
prolin
Short chains have ATPase activity
important for muscle contraction
Molekular heksamer asimetrik
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Miosin + Tripsin 2 Meromiosin
LMM heliks
not ATPase activity
not binding at F-aktin
HMM Fibrosa + globular
Have ATPase activity
Binding at F-aktin

+ Papain Fragmen S1 dan S2

not ATPase activity
not binding at F-aktin

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Hydrolysis ATP movement
Cycle of Muscle contrction

H2O
Aktin ATP - Miosin
5 1
Aktin Miosin
ADP Pi - Miosin
ATP
ATP 4 2 Aktin

Aktin - Miosin 3
Aktin-Miosin
ADP-Pi
ADP
+
P1 55
Muscle Contraction

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Pathway of ATP Resynthesis
Resyntesis ATP 4 methods:
1. Glycolysis :results piruvat and
lactat
2. Oxidative Fosforilation
3. Creatin phosphate
4. Adenilat Kinase System

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OXIDATIVE FOSFORILATION
Needs O2 suplay
O2 binding by myoglobin
Myoglobin >> red muscle
<< white muscle
Glucosa Blood glucosa
Glycogen endogen
Fatty Acid Tg (Adiposa)
Major substantion for aerob
metabolism of muscle 59
Creatin Phosphat
Major Storage energy at muscle
Creatinphosphat
ATP + Creatin
(Muscle Relaksation)

Creatinkinase

Avoid faster depletion of ATP

with source to result
ATP from ADP

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Adenilatkinase interkonvertion AMP,
ADP, ATP
Adenilatkinase katalizated 1 mol ATP & 1 mol
AMP forming from 2 mol ADP
ADP + ADP ATP + AMP
AMP + H2O IMP + NH3
IMP + H2O Adenosin + Pi
Adenosin + H2O Miosin + NH3
AMP, Pi, NH3 activated Fosfofruktokinase

(PFK-1) 61

Induced muscle glycolysis at sprinter.

Sprinter used creatin phosphate (4 5
second at the first) + glylcolysis
anaerob from muscle glikogen source
glucosa
Marathon runner used fosforilase
oksidatif with aerob metabolism as
source ATP and
Blood Glucosa and Free Fatty acid dari
trigliserida (Adiposa)
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TUBULIN DAN DIENEIN
Sel bukan otot : sperma Flagel/silia
bergerak sistem mikrotubulus tubulus
tubulin
Tubulin : Protein dimer yang berbentuk tabung
berongga yang kaku.
Dienein : Protein berupa sepasang lengan yang
terletak sepanjang mikrotubulus
Neksin : Protein berupa pita yang elastis yang
menghubungkan tubulus ganda bagian luar

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PERGERAKAN BIOLOGIK

Aktin Miosin Tubulin Dienein

- Kontraksi Otot - Debaran sillia dan
- Pergerakan amuboid flagella eukariotik
- Aliran Sitoplasma - Pergerakan kromoson
- Debar mikrovilli usus pada mitosis
- - Pergerakan vesikel
Pembelahan sel pada
mitosis sekretonik

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SPEKTRIN DAN ANKIRIN
Keduanya membantu menentukan bentuk serta
fleksibilitas sel darah merah
Spektrin : protein utama pada sitoskleton terdiri atas
2 polipeptida (rantai dan ) tersusun anti paralel,
terjalin longgar berbentuk dimer dg 106 asam amino
Ankirin : protein berbentuk piramid yang mengikat
spektrin sensitif terhadap proteolitik
Abnormalitas spektrin eliptositosis herediter
Abnormalitas ankirin sperositosis herediter
Abnormalitas spektrin dan ankirin menyebabkan
anemia hemolitik
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REFERENCES
Harper Biochemistry
Medical Biochemistry
Skletal Muscle from Molecules to
Movement
Color atlas of Biochemistry
Biochemistry illustrated

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