NMS -

2011



lippincott's illustrated review
biochemistry NMS-biochmeistry .
. )
(
.
.
.
NMS- biochemistry
. USMLE
.

.
. 1999 2001
.
.
2011
.

.

.
.

 0

-I ) (:

.
. .
.
-II ):(Functional groups
.

) .(0-1

:0-1

-one ) . (acetone ) (
) (-ol ) (methanol )(acyl
) (tri-acyl-glycerol .
acyl .
-III :
.
) ( COO ) (-PO42- ) (-SO4- . PH
).( 0-2


. PH .
5 .

) (
).( 0-3
-IV :
.
- -
.
+
C = O

)( - .
:0-2 ).( 0-4

.

:0-4 -
- -.
:0-3 .

-V:
. ) (catalist
.
.
.
)
( ) (NaCl Cl
Na . )
( .
) (hydration shell .

 )(
. ) (hydrophobic
) (interaction .
) (amphipatic
)(
)( .
.
-VI:
) ( ) (
. )(

.
A
.
. ATP
AMP-fatty acid .
COA-SH

.
)
( .

.
) (-SH
.
) ( .


) ( anhydride ) .(0-5

:0-5
.

 -VII :
5 :
-.
1 ):(Group Transfer
. .
. ATP

ATP ) ( -6- :

+ ADP -6 +ATP

2 ):(Cleavage Reaction
.
. .
.
3 ):(Condensation Reactions
.
) ( ).( 0-5
4 ):(Rearrangment Reactions
.
.
5 ) :(Oxidation- Reduction
.

. .
.
) ( H o ) ( H oo .
) (
.

) .(0-9
. O2
O2 H2O H2O2 :
CH 2 CH 2 HC = CH
C OH C = O
-VIII :
):(0-6

 -1 .
-2 ) ( ,,,
.

:0-6 .

. .

 1
PH
:
. %75
.

.
)( NaCl
Na+ Cl + .
:
.
) 1-1 2-5 ( . .

4/5kcal/mol O-H
110kcal/mol .


.
1-1
.
: ) (H+ ) (OH-
H 2O H + + OH :
2 H 2O H 3O + + OH :
H3O+ . 55/6
) (mol/l . Kw Kw=[OH-][H+] :
. H+ Kw = 11014 25 C
] [OH- ] [OH-][H+ 1 1014 25 C
. OH- ] [H+ .
:
) ( )
( %5 .
) : (Bronsted-Lowry
.
) ( HA H + + A :
HA A- ) ( A- .

 .
1-1 . ) (Ka :

Ka = H + A HA

Ka HA H+ A- .
Ka .
: )( .
. Ka
Ka .

1-1

:
) (HA .
[H+] Ka -1
log H + = log Ka log HA A :

] PH= -log[H+ Pka= -logKa

PH

)
( PH .

: 1-2

 : ) (HA
PH
PH ) .(1-2
:
HA H + + A : ) (OH- H+
) .(H+ + OH- H2O H+ HA
HA ) H+ (
HA + OH H 2O + A :

PH :
PH -1 ) ( PKa
]PKa log[HA
= PH :
2
-2 PH : %10 %90 PH
. 0/2 PH Pka=3.9
PH=3.9+log(0.2/0.8)= 3.3 :
) %50 (
)] ([HA]=[A- [A-]/[HA]=1
PH=PKa .
PH -3 : ) PH (equivalence 7

HA + OH H 2 O + A . HA
A- H2O OH- HA . OH-
PH 7 ) OH-
PH 7(.

:
PH .
)(HA ) (A- . )]([A-]/[HA
PH pKa ) . (pH=pKa )
( ) . PH %50
(. PH PKa1 )(PH=PKa1
PH PKa .
1-2 ) (CH3COO- PKa=4/8
PH 5/8 (PH=4.81) 3/8 PH=4/8 .
PH .

 : PH PKa ) (CH3COOH PH
PKa ) (CH3COO- .
:
PH PKa .
.
:
A-
) HA (

A-:
:

HCl + CH 3COONa NaCl + CH 3COOH

:
NaOH + CH 3COOH CH 3COONa + H 2O

-:
-1 PH
.
-2
) ( PH .
PH PKa .

PH .
-3 PH
.

HCO3- (pCO2) CO2 PH
).(1-3A
:1-3 -
PH
HCO3-
) (A )(B
.

-4 PH .
) (1-3B

 +
DH D + H :
+ +
BH B + H :
) ( ) (DH

) ( D . ) ( ) (B
+
) ( BH . PH
) PKa ( .
PH
) PH=1/5 (PH= 7/4 .

PH:
-
)(CO2 ) (HCO3 PH .
CO2 PH . CO2
H2CO3 HCO3- .
CO2 H2CO3 CO2
HCO3- :

CO2 + H 2O H + + HCO3

PKa 6/1 PH . 7/4 .

HCO3- CO2 PH
:
PH = Pka + log [ base] [ acid ] 7.4 = 6.1 + log HCO3 CO2
1.3 = log HCO3 CO2
anti log1.3 = HCO3 CO2 = 20
CO2 CO2 ) (pCO2 . pCO2
] [CO2 [CO2] = pCO2 0/0 3 :
0/0 3 CO2 38 C mM/mmHg . PH 7/4
pCO2 = 40 mmHg [HCO3-] =24 mM . CO2 HCO3-
PH 7/4 .

PH:
PH . PH 7/4
) (acidosis 7/4 ) (alkalosis . PH CO2
) (respiratory alkalosis . PH CO2
) (respiratory acidosis . PH HCO3-
HCO3- .

 PH .
) . (1-2

:1-2 -

HCO3 pCO2 PH HCO3 pCO2

______ ______

______ ______

______ ______

______ ______

PH - .
PH
PH
PH .
PH .
)(HA ) (A- . 1 PKa
pH=pKa] [HA]=[A- . PH .
- .
. PH 7/4 7/4
. PH CO2
. PH
HCO3- HCO3-
.

 2

:

.
.
: :
-1 -2
)
( -3

-4

-5
-6


.
.
.

).(2-1 .

: . 10-50 ) (Kdal
350 dal 1000 Kdal .
-I :
300 20
. 20 DNA .
:
) ( ) (-COOH ) (-NH2
) (R ) (
) .(2-1
: 20 ) (iminoacid


)(imino group -NH- ) .(2-2
.
PH ) (7/4
) (COO-
) (NH3+

)
(
) .(2-2
.

:
-1 -2 )
(.

).(2-3 .
. PK - -
.

 -1 :
) (2-3
)( .
-2 :

PH ) .(2-4

) .(2-4 20 .
PH .


) .(2-5

.
PH .
-3 :

.
PH
2-5

PH ) .(2-4
-4 :
.
PH
)
+1( ) (2-5
PH




.

:
)(
.
) 2-6 (:
-1
.
C
Cystein
-2

Glycine Glutamate G
2-6 . G .

-3
Phenylalanine F
W .
-4 ) (
. L ) (Lysine KL
Asx . ) (Aspartate )
Glx . (Aspargine ) (Glutamate
) . (Glutamine Asx Glx 4 B Z X
.

:
DNA .
20 )post-
(transcriptional modification . 100
.
:
-1 )(-OH
-2 ) (-CH3
-3 ) (-COOH
-4 ) (-PO3
.
) (.
-5

:
) (

.

.
) : (Enantiomer
L D
2-7 D L ) .(2-7
.
)(stereoisomer
) (Dextrorotatory ) (Levorotatory .

 L . D
.
)( :

) ampholyte (amphotric electrolyte .
PH pKa :
PH pKa .
. PH PKa
.
. PH
)(7/4 )(-COO
) (NH3+.
-1 :

. PH
) .(2-8 )
(
PKa . ) (PK1 2/3 PKa
) 9/1 (PK2 ) PKa PK1 Pka
PK2 PKa
PK1 (.
PKa : PH
. PH
)( ) (2-9
) PH (
) (COO
.2-8 .

).(2-9 .

 ) II (2-8
. ) (zwitterion )(
.
PH
III ) .(2-9
K PKa
PH .
PH :
] PH = PK + log [ II ] [ I ] or [ III ] [ II

PH ): (pI
PH ) ( PH
PH . PKa pI
zwitterion . )
( PH ) 5/7 = [9/1 +2/3]/2 2-9 ( . pI) (
PKa ) zwitterion PK1 PK2( PH zwitterion
) zwitterion I (III
.
:
PH ) PK1 (PK= PH11 COO/COOH PH=PK1
I II . PH ) PK2( PK= PH21
NH3+/NH2 PH=PK2 II III
. .

.
-2 :

:
. ) (PK1=1/8
) (PK2 =6 ) (PK3=9/2 . PH
.
: PK2=6
PH .
PH : ) (
PKa pI = ( PK 2 + PK 3) 2 = 6 + 9.2 2 = 7.6 :


PKa . PKa 2-3 2-4 .

.II :
) (

.

) (2-10 A
)(endergonic


.
:
-1 ) (-C-N-
) (2-10 B
)
(
)
R(
.
-2 .

.
-3
R )(Cis
).(2-10 B
-4 -NH -C=O PH 12 2


.

).A.(2-10
valylalanine
B

 .

) N (C
.

) (HPLC .

:
)
(conformation . .
4 : ) 2-11
(.

-1 ) (primary structure:

DNA
.
.

.
.
:


N ) (N-terminal amino acid
C
) (C-terminal amino acid .
N C .
. 2-10 A
Val-Ala . Ala-Val
:

.
ine ) (Glycine ) an (Tryptophan
ic ) ate Glutamic acid (Glutmate
).(2-11 . -yl .C

 N C ) (
) Valylglycylleucine : (.

-2 ) (secondry structure:

)( .

.

) (
DNA
. (- sheet)
(-bend)
.

).(2-12 )(-helix ) (-C=O -NH-
. .
-bend (-turn)
.
:( -helix)

) .(2-13
: .
) (-C=O -NH- 4 .
.
3/6 ) 3/6 (
3 4 .
L ) (right handed
.
:
- .

. ) (
.
) ( ) (
.

 ) (keratin
. .
%80 .

(-sheet)


) (silk fibroin .

. -C=O
-NH-
) .(2-13 A
) (interchain hydrogen bond .


) -strands (

) (antiparallel -sheet ) (2-11 B

N
) (parallel -sheet ) (2-11C

.
:
C-C ) (tetrahedral
)(
(-pleated sheets)
) (2-13 A
.
.A 2-13 .B
.C

.

 -NH-
.
)(amyloid protein
.
) (fibrous proteins .
) (Alzheimer's disease
) fibril (
. .
(-bend) (-turn)

)( .
. -bends
) -bends .(2-13 4
) ( .
-bends . .

)(nonrepetitive-secondry structure

) (loop ) (coil
.
random coil .

) .(2-14 . .

)(motifs
) (
.
.
) ( .
2-14 . DNA .
helix-loop-helix .

 -3 ) (tertiary structure:
) domanis
(
.
.
.
)(globular .
) (




.
.

.



.

. 2-15

.
)(domains
)
( .
200 2
).(2-15 . .
)
(
.

. )(
.
:

 -1 : ) (-S-S-
) (-SH
.
) (Cystine ) .(2-16


) (

.

.

.
-2 :

).(2-16 ) .(2-17
.
) ( )( .



)( ) .(2-18
.

) (2-18 ).(2-17

 -3 :
)
( )
( ) . (2-18

.
-4 :
)
( ) .(2-19

).(2-19
.



.
.

.
:
) (chaperones
. (PCB proteins) polypeptide chain binding protein
) (heat shock protein
.
.

-4 ):(Quarternary structure
) monomeric
(proteins .
. ) (subunit )
(protomer .
.
) (dimeric ) (trimeric
) (multimeric ) (multiple subunits . )
( .

 .
.
.

.

:





. ) (amyloid
) (neurodegenerative
.
) (A 40-42 .

.

.
) amyloid
(precursor protein
) .(2-20
. . -10 %
5 .

. ) (tau .

.

2-20


) (PrP
) (scrapie .
) ( .
(Sc=scrapie) PrPSc
.
(C= cellular) PrPC
PrPC

PrPSc

) .(2-21
) (PrPSc
.

.
.

):(protein denaturation


.

.

2-21

.

. .

):(protein purification

.
.
.

 .
.

:
-I : :
:Salting out -1 ) (
.
) ( .
:Salting in -2 .

.
-II
-1 )(ion- exchange chromatography
)(
) (polyanionic ) (polycationic
.
) (2-22
(anion-exchange
) chromatography . PH

.
.

2-22
.

.
.
) (
.
-2 )(high performance liquid chromatography
) (HPLC .
.
. HPLC
) 1000 5000 (
.

 -3 )(electrophoresis
.
) (charge/mass .
. PH
. PH ) (pI PH
. PH pI
. PH pI
.
.
:
) (a : .
) (matrix ) (agarose gel
) (polyacrylamide .
.
.
.
) (b ) (isoelectric focusing
) (pI .
) ampholines
( pI PH .
PH pI
) PH (
PH PH pI . pI
pI .
)sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)(c
) (

)free zone capillary electrophoresis (d

)( )mm
0/3 (0/05 .
. ) (10 kv
.
) ( .
-III )(molecular size
-1 ) :(dialysis
) (semipermiable memberane
.

 .
) (pore size .
-2 )(gel filtration
) molecular
(exclusion chromatography
) (molecular sieving .


) (porus beads .



) (2-23

2-23

)( .
.
-3 )(ultracentrifugation
.
.
. (svedburg units) S
.
-4 : SDS
)(SDS
- ) (-mercaptoethanol
. SDS .

) SDS .(2-24

-SDS
SDS
) ( .

.

 - IV

-1 ) affinity
(chromatography


)
ligand ( .



.



.

2-24 SDS

) ( .
.

.
-2
) ( .
)
( . )
( .
. ) rabbit anti-gamma
(globulin anti-IgG ) (
.
.

:

.

 .
:
-1 : 110 C 24

.
-2 ) : (Chromatography
.

PH . PH

.
PH .
-3 :
) (ninhydrin .
)

( .
.

.
.

.

aminoacid analyzer ).(2-25
2-25

:N
N )(phenylisothiocyanate
)(Edman's reagent . N
-) (phenylthiohydantoin ) (2-26
) N (
.
. ) sequencer (
100 N .
100 sequencer .
.

 ) (
.
.

).(2-26 .

-1 : ) (trypsin
.
.

) .(2-27
tryptic peptide .
-2 :
)(cyanogen bromide
.
.
) . (2-27
.

:

.
).(2-27

.

.

. 2-18

.

 :

. )(guanidine hydrochloride

) (performic acid

.

:DNA
DNA
.

) ( .
) ( .

) (
. PH 20 .
.
.
. .
) ( .
L.
) ( .
) (
.
.
. .

.

.
.
. 2-28 2-29 .

 2-28 .

 2-29

 3

.
.
) (
:
-I )( .
-II
-III .
-IV -V .

-I :


.
)(myoglobin
) (hemoglobin .
) (hemeproteins .
) (heme .
) ) (prosthetic group( .

. ) (cytochromes


. )
(

).A.(3-1 .B ) (heme .
.
: heme
heme (protoporphyrin IX) IX (ferrous iron Fe2+) II
) (3-1 IX ) (pyrrole
IX IX .
.

 6
).(3-1

:
.
153
. %80 %75 8 . A H )
. (3-2A ) (
-bends )(Loops . ) (

)( .
:

) .(3-2B
)(proximal histidine F ) His-F8
F( His-F8 .
) (distal histidine E ) . (His-E7 His-E7
. His-E7
. ) apoprotein apomyoglobin
( .

.B . ) .A.(3-2 ) A.( H

:
heme

) ( .
) .(3-3
) (oxygen-dissociation curve .
) (pO2 .
. ) ( Y

 ) ( ) %100
( .
) 20 mmHg (torr %90
. ) (Y
:
]Y = [ MbO 2] [ Mb ] + [ MbO 2

:Y ) ( [MbO2]
] [Mb .
%50
P50 .
).(3-3
.

P50 1mmHg 26 mmHg

P50 .

.
. ) (MbO2 ) (Mb :
Mb + O 2 MbO 2
) (
.

:
) (RBC; Red Blood Cell
. 5 RBC 280 RBC
.
RBC
.
) ( 4 .
) (subunit . ) A
( : ) .(3-4 )
( ) (hydrophobic pocket
.
.

 ) .A.(3-4 .B .

:
()1 ()2 .
. ()1 ()2
) .( 3-5 ()1 ()2 .
) (
) ( ) (
) .(3-5

) .(3-5 .

:T ) T Tense Taut (
. T ()1 ()2
. T .
: R ) (T
R
R ) Relax
( . R ) .(3-5

 :


.


) (sigmoidal) .(3-3

pO2
pO2 ) ( .
): (cooperative effect



) .(3-6
.

) . (3-6 ) (heme-heme interaction

.
30 mmHg 20
) .( 3-3
): (Hill coefficient
) (n . Y )(
P50 %50
) ( pO 2
n

=Y :
( pO 2 ) + P50
n

n ) ( . n = 2/8
n = 1.
):(allosteric effects
) ( PH ) ( CO2
) (pCO2 2 3 . ) allosteric
other site (
.
.
-1 :

. ) (deoxyhemoglobin 0/4

 .
. .
His-F8 F
C .
) (

.
300 .

) (
) lungs
(alveoli ) (loaded
) ( ). (unload

) 3-3 .(3-7

.

) (
)
( .

).(3-7 CO2 .

-2 PH
PH ) H+ ( CO2


) .(3-8 PH CO2
.
).(3-8 PH . ) (Bohr effect . CO2
PH .
: CO2 CO2
) ( CO2 . ) carbonic
CO2 + H2OH2CO3 (anhydrase :
H2CO3H+ + HCO3- :

 PH . PH
PH .
PH .
: -N
PKa ) (
) ( ) PKa
( ) (
R T .
Hb 4O2 + 2 H + Hb 2 H + + 4O2 :
PH = 7/4 T R
.
CO2 :
CO2 CO2
) CO2 .(3-7
Hb NH 2 + CO2 Hb NH COO + H + ) (carbamate :
CO2 R T
. CO2
) ( . T
R CO2 .
) (hyperventilation
. CO2
. ) (numbness
) (muscle cramps ) (dizziness.
) :(CO
) (hemoglobincarboxy HbCO .
CO R



) .(3-9
220 CO CO
HbCO
3-9 . %60 HbCO .
.
CO ) (hyperbaric oxygen therapy
. CO . CO
)( . CO2 CO

 ) (NO NO .
.

-3 2 3 )(2,3-BPG
2 3 ) (2,3 bisphosphoglycerate 2,3-BPG .
RBC .
) ( 2,3-BPG .
T T
) 2,3-BPG (
. 2,3-BPG :
HbO2 + 2,3-BPG Hb-2,3-BPG + O2
: 2,3-BPG 2,3-BPG 2,3-BPG .
.
. .
2,3-BPG )(
) .(3-10
.

).(3-11 2,3-BPG . ).(3-10 2,3-BPG .

: ) (
) (pulmunary emphysema 2,3-BPG
. 2,3-BPG
. 2,3-BPG
) .(3-11
2,3-BPG 2,3-BPG : .
) (

 2,3-BPG RBC .
.
2,3-BPG
. 48 24 2,3-BPG

. ) (hypoxanthine-ribose 2,3-BPG .
RBC
2,3-BPG ) (.
: ) CO2 (2,3-BPG
.
.
2,3-BPG .

) (Fe3+
) ( methemoglobin ) (metmyoglobin .
Fe3+
) Fe3+ ( .
.
(HbM) M .
:

NADH b5 ) NADH-cytochrome
(b5 reductase RBC

. ) ( .
:
) (CN .
. ) (amyl nitrite
.
.

:
.
.
. ) .(3-12
:

 -1 %98 :(HbA1) A1 HbA1 HbA1 .

) 2 2 ( . 141 146
.
-2 :(HbA2) A2 )(%2 HbA2
) HbA2 . ( 2 2 .
) (3-12
-3 :(Hb Gower1) Gower1
)(embryogensis

) (embryonic hemoglobin
.
) (Zeta ) ( ) ( 2 2
Hb Gower1 .

).(3-12 .
) : (.
-4 : (HbF) F
Fetal ) HbF
(hemoglobin HbF .
) .( 2 2 6

HbF .
%60 RBC HbF .

. HbF
. HbA . 3-13

. HbA
HbA HbF .
: HbF HbA .
HbF HbF
.
HbA HbF ).(3-13
. HbF
. HbF 2,3-BPG
) ( HbF
) ( . 2,3-BPG . 2,3-

 BPG HbF 2,3-BPG HbF

HbA HbF .
2,3-BPG HbA HbF .
HbA HbF 2,3-BPG .

-5 (HbA1c) A1c
HbA1 ) (
.
)(glycosylation .
.
HbA1 HbA1 . HbA1c .
) NH2 (
) .(3-14 HbA1c
) (
%12 .
120 HbA1c
4 2 . HbA1c

).(3-14 .
.

) - globin-like chain (
).(3-15
:(-gene family) 16 .
) ( ) ( .

) (pseudogenes.

).(3-15 .

 : ( -gene family) 4 )
( 11 .
) A (G HbF HbA2 .
: mRNA .
) (interons
) (exons mRNA .
mRNA
) .(3-16

:
) (hemoglobinopathies
)
(
.

) ) (Sickle-cell anemia
(HbS (HbC) C
HbS . HbC

.
-1 )(HbS
) S
( .
500
. %0/3 HbS
) (HbS %13 8
3-16 .

. HbS )
( . s
2 2S HbS.
: HbS HbF
. RBC 120 15 10
.
. .
. HbA HbS
sickle-cell trait .

 :

) (3-17 S
. )
( ) (
HbS HbA . HbS
) ( HbA ) -18
.(3 trait
)( .
:HbS )(
)(
HbS . HbS RBC

. HbS
. RBC

) (anoxia
).(3-19
:HbS
) .(3-17 HbSHbC RBC HbS
) HbS ( .

CO2 PH
2,3- BPG RBC HbS HbS .
RBC .
HbS : ) trait
(HbS )
(
) .(3-18 SA C . ) (
.

. RBC .

RBC .
.
: ) (
. )(

 .
HbF
RBC .

3-19 .

-2 (HbC) C
.
RBC . HbC
. HbC HbA HbS
. ) (HbS
. .

-3 (HbSC) SC

HbC HbSC
.
HbSC ) (crises . HbSC
)
( .

 -4 (HbM) M


.
) ( Fe +3
.
RBC
- ) (chocolate cyanosis
.
.

.

-5 )(thalassemia

.
.
.
2 2 A.
.

:
-1 ) (deletion
-2 ) (promoter
-3 mRNA
.
-4 ) (frame shift ) (nonsense
) .A.(3-20 - -.
.B - .

. ) 0thalassemia
( ) 0thalassemia (
:
.

 ) + thalassemia ( ) + thalassemia (.
: . 16
) . 4 ( -
) :(3-20
-1 ) (slient carrier
.
-2 -thalassemia trait .
-3 3 , (HbH) H
) trait(.
-4 hydrops fetalis
HbF .
- 4 ) (Hb Bart
4 ) (HbH .

. .
: .

.
:
-1 -thalassemia trait -
thalassemia minor ) .(3-21
.

HbA2 HbF .

.


.
-2 -thalassemia major
) .(3-21 ) .A.(3-21 - -.
.B -
.

) (homosidrosis .
.

 -II:
%65 %55
.
:
-1 :
.
:
-a : . .
-b :
.
-c : .
.
-d : .
-2 :
.
:

.
PH .
. ) (domain
) (subdomain .
.
:
-1 .
-2
.
-3 ) (edema

.

 -IV :
) (collagen ) (elastin ) (keratin ) (fibrin )(fibrous protein
. .
) (sclera ) (cornea
.

.

. 150 30 25 15 13
.
:
. 12
. .
.
) (extracellular matrix ) (vitreous humer
) (tendons
.
.
.
:
(-chain) .

) (triple helix ) .(3-22
)
NH
-C=O (
.
.

).(3-22

.
: ) 1000 (
.
. 1 1 2
) ) ( (1 ) 2 ( 2 2 1 .
) 3-23 (:

 -1 : 2 1 3
.

) .(3-24 1
2 .
3
.
-2 : 4 7
4

) .(3-25

.
-3 : 9 12
).(3-23
.

3-24 .

: .
) (1 % 33 : ) % 10 (Gly ) %10 (Pro ) (Hyp %1
) .(Hyl
%60 . Gly-X-Hyp Gly-Pro-X ) X
( % 40 .
Gly . -)n
(Gly-X-Y- X Pro Y Hyp Hyl
) (-Gly-Pro-Hyp-)333 : .(3-26

 ).(3-26 1 ].Hpy:
: : Hyl [

3-25
4 .

Hyp Hyl


) (3-27 .
.
) (left-handed
(-helix)
) ( ).(3-27
.

. ) (polyproline .
.
) (pyrrolidine .
) (triple helix
.

:
-1 :(pro -chains) )
( .
mRNA
) (Rough Endoplasmic Reticulum .
-N ) (signal peptide
. mRNA RER
. RER

 ).(3-28 .

 RER . mRNA
)(preprocollagen . pre .
RER ) (signal- peptidase ) .(3-28
150 N 250 C
)(propeptide .
.
-2 :
RER
) (hydroxylation ) ( .
) (triple- helix .
-a : pro -chains RER
:
) :(lysyl hydroxylase Gly-X-Lys
-5 Gly- X -Hyl .
-4 ) :(prolyl-4-hydroxylase Gly-X-Pro
-4 . Gly-X-Hyp .
-5 ) :(prolyl-5-hydroxylase Gly-Hyp-Pro
-5 Gly-Hyp-Hyp .
: - (ascorbic acid) C )( -ketoglutarate
Fe 2+ ) (3-27
-b : .
) -O
( C ) - N( .
:
-1 ) (galactosyl transferase Uridine ) UDP-galactose
(diphosphate-galactose .
-2 ) (glucosyl transferase UDP-Glucose
) .(3-28
-c : triple helix
(pro -chains) .
C .
-3 :

) (procollagen .
. ) -O(
.

 -4 :
N C C N
) N (C triple
helix ) ) (tropocollagen (.
-5 :

. 3/4 .
) (collagen- fibrils
) (collagen fiber ) (3-28

) ( )cross-
(link .

) oxidative
deamination (


) (allysine
) (hydroxyallysine) .(3-29

) (
) .(3-26

) (aldol codensation .

) .(3-29 . .

.

)(elasticity
.
:

.
) (collagenase .

 )(
.

:
.
. .
-1 )(scurvy
) C ( . C
C
.
: C


.
C
.
:
) (3-30
)(osteoprosis
: C
.
3-30 C . .
.

-2 ):(osteogenesis imperfecta
) (brittle bone syndrome .
.
: .
) (3-31 )humped-
(back .
.
: I osteogenesis imperfecta tarda
1 2 . II ) osteogenesis imperfecta
(congenital .

 1 2
1 .


.

RER .
1

3-31 ) type . 1 1
.(II .

2.
: .

-3 ):(Ehlers-Danlos syndrom
. 10
.
: ) (3-32
.

.
:
.
.
3 1
3 .
).(3-32 .Ehlers-Danlos 3

. 3
1
.
:
. III Km
C ) ( C
.
V . -D

 ) (D-penicillamine
.

-V ):(Elastin

.
) . .(3-33

:
:


.
:

.
).(3-33 .
.

)(desmosine
) .(3-34
.
) (
.
)(fibrilin
.
1 ) (Marfan syndrome
- . ).(3-34 .
.
: ) (elastase .
) ) (protease
) (proteinase (
) .(3-35

 - 1 ) :( 1 antitrip sin
-1 ) ( 1 AT
. - 1
)
( . 1 AT 1 AT .
% 90 1 . 1 AT

. 1 AT
.
: 1 AT
.
1 AT
) ( ) .(3-35

) (emphysema . %2
1 AT .
1 AT 1 AT
.
GAG AAG
) (342 .

.
1 AT . )
( 1 AT
. 1 AT
).(3-35 . 1 AT
. 1 AT
.
1 AT.
: 1 AT 1 AT 1 AT .
.
.

 -VI ):(-Keratin
- .

) (intermediate filaments
- .



- .
.
.
) (protofilament

) .(3-36
. 3-36

A ) (Hb ) :
(22 .
. T
. Hb
Hb R
. R . Hb
.

. Hb PH pO2 pCO2
2,3-BPG . O2 Hb PH CO2 ) (
. .
2,3-BPG RBC 2,3-BPG . Hb
.
) (Hb CO .
.
SC C
.
.
.
. )(

 . .
- 1 .
. - 1
. 3-37 3-38
.

 3-37 .

 3-37 .

 4

.
) (
.
:
1 2 .
.
:
-1 RNA )(ribozyme )
( .
2 ) (.
3 PH .

-I :
1 :

) .( 4-1
) (ES ES
) (EP
).(4-1 .
.

2 ) : (Turn Over Number 153-158

.
. S-1 min-1 TON . ) (Kcat (TON) Turn Over Number
Kcat . .
3 : )
( ) ( .
.
:
-1 ) : (look and key theory .
-2 ): (induced fit theory
.

4 :
. )
Zn2+ (Fe2+
) NAD+ .(FAD+
) (apoenzyme
) (holoenzyme .

) (cosubstrates ) (NAD+
) (
) (prostetic group FAD+
.
5 :
) ( .
6 :
) (4-2

.
).(4-2
.
-II ) ( :
:
-1 .

.
-2 .
-1 :

.

)( . AT*B A
)* (T .
) ( ) -3
.(4
) (transition state.
).(4-3
.

 : .
.
.
.
.
2 :


. .

.
) (
.

.
) general acid-base catalysis (


)
( . )
( .

) ( ) (

.
) .(4-4


) (ES
) ( .
)(
4-4 .
-
.

 :
) in vitro
( . PH .
.
M/min (velocity) V
.
) in vivo (.
1 : )(optimum ).(4-5
.
.
35-40C 40C
70C .
2 :PH PH )(4-6

).(4-6 PH . ).(4-5 .

) (-NH3+ PH .
PH

PH . ) (optimum PH PH
PH =2
PH
PH =2 . PH
).(4-6
3 :
.

).(4-7 .

 4 :

)(Vmax) .(4-7
.
.
1 )(first order

) (zero order
) .(4-9
: ) (sigmoidal
.

).(4-8 :
1 Km 2
Km. . ) (E
) (S - ) (ES
) (P ) K1 K 1
K 2 (:

:
:
] Vmax [ S
= V0
] Km + [ S
) = V0 = Km
=[S] K 1 + K 2 K1 = Vmax (

:
1 ] [S ] [E E
S .
2 [ES] :Steady State ES
).(4-9 ) ES E S P ( E .
.

3 ) (V0 . P
P S .
E S .

 :
1 ) Km ( : Km .
) 4-8 .(4-9 Km
Km )
Vmax ( Km E S ) Km .(4-8
.
2 : ] [S Km ) (first order ] [S
] [S Km
) .(Vmax ] [S mixed-order
).(4-9
-3 : .
) (V0 ) (Vmax .

:Lineweaver- Burk V ] [S
Vmax Km ) asymptote (
:
1 Km 1 1
= +
V0 Vmax S Vmax
1 V0 1 S -
Vmax Km
) .(4-10 ) Y-
(intercept 1 Vmax ) (X-intercept 1 Km
. ) (slope Km/Vmax.

-III :

. : ).(4-10 . Lineweaver- Burke

A :
.
B :
.
A :
:
1 : .
Vmax Vmax

 Vmax Km
) .(4-11 ) (Ki EI :
EI E+I Ki=[E][I]/[EI]: Ki I E ES
Ki .

) (4-11 ] .A .[S - .B Lineweaver- Burke

.

y ) Vmax (
) x (1/Km Km
) .(4-11B
.



. .
) (Lipitor ) (Pravachol

) (HMG-CoA reductase
) (HMG-CoA ) .(4-12

4-12 HMG-CoA .
HMG-CoA reductase

2 ) : (Uncompetitive Inhibition ES
. Vmax Km ) Ki (4-13
ESI ).(ESI ES+I

 3 ) Non Competitive
: (Inhibition
.
ES
EI ESI )-14
.(4 ESI P ES P

4-13
.A - .B-.
Vmax
Vmax Km
)-15
.(4 )(Pure Non Competitive Inhibition
E ES
) (Mixed Non Competitive Inhibition
E ES .
:
.
) Fe2+ (
.
. ).(4-14
- .

) (4-15 ] .A .[S - .B Lineweaver- Burke

.

 B :
. .
:
1 : Affinity Labels ) (
.
. .
2 : Suicide inhibitors
.
.
3 : Transition state analogs )(transition state
.
.
.

:
.
II . )AngiotensinConverting Enzyme
) ((ACE I II ) (Captopril ) (Enalapril
) (Lisinopril . II
. ) sarin (
.

-IV :
.
.
.
Km
.

:
1 :
a :
) (
) ATP (
).(4-16
).(4-16
.

 ) (
) ( .
) ( .
.
-b ) :(nucleotidylation ) (
. .
-C ) :(proteolitic cleavage ) (proenzyme
) (zymogen
.
) ( .
.

2 :

) (committed steps
.
) )(effector
( .
) (

.
) (positive effectors
) (negative effectors .
:
a : homotropic effectors
homotropic .
.

)
( ) (cooperactivity .
( ( ) ).(4-17 )
.A. Vmax .
. B .K 0.5

) .(4-17

 . Vmax ) K0.5
( ).(4-17
b : heterotropic effectors .
heterotropic) .(4-18
. 4-18 D
E G
.
G )
(
.
) (feedback inhibition .
).(4-18 .
.
) ( . )
( .

3 :
.
.
. .
) ( ) (.

4 ) : (product inhibition .
. 4-19
.

) .(4-19 .

-V :
A ) : (trivial ase ) urease .(sucrase
) (pepsin ).(trypsin
B : ) (IUBMB 6)(
) (subclass ):(4-20

1 ) :(Oxidoreductases
.
2 ) :(Transferases
) ( .
3 ) :(Hydrolases
) (.
4 ) :(Lyases
Co2 . C-C
C-S C-N .
5 ) :(Isomerases
.
6 ) :(Ligases
ATP
.
4
) 1 (6 ) (subclass
subsubclass subsubsubclass
.
) (
Lactate - NAD+ - Oxidoreductase :

-ase Lactate dehydrogenase :

) 6 .(4-20 .

-VI :
1 ) : (IU 1
. mol/min
2 ) : ( Katal 1 ).(mol/s
3 ) : (Specific Activity ) (IU .
.

-VII :
1 :
.
.

 .
) ( .

) (4-21 ) (A ).(B

:

. .

) .(4-21

.
) (

) (ALT / ) (GPT
ALT
.
.
.
:
) (
) (isozyme
.

.
.
) (Creatine Kinase
(Brain) B (Muscle) M .
) .(4-22 M B ) (CK CK2 (BB)CK1
.

)(MB .(MM)CK3
) .(4-22 1
) (CK1 CK2 .CK3 CK
CK1 CK3 .
CK2 CK3.
CK2 :
CK2 . 4-8 CK2
24 48-72
) .(4-23
(Troponin T) T (Troponin I) I
. I ) (cTnI
4-6 cTnI .
8-28
3-10 cTnI
CK2
. ) (LDH )(AST
. LDH 3-6 ) .(4-23 ) (CK2
.

) 48 ( CK2 .

2 :
) ( .

. .
.
- ) (ES .
) ( ES EP
.
.
-
. .
) Km ( ) Km Vmax (
) Vmax Km ( .

 ) ( . )
( .
. ) ( ) (
.
. .
. 4-24 .

) .(4-24 . =S :=[S] =P =E =V =Vmax

= Km = K0.5 .