BIOXHMEIA T

1.

, ,
, .

.
.
( )
. ()

.
,
:
) , ' ,
,

) ,
(messengers), .
, .

,
.
(.1): ) , .
() '
, .. ) , .
( ) '
, .. )
(
) ( , ) ..
)
() .. .




.


,
""

(signal)
-

.


.

(,
)

1
 ""
1904 William Bayliss & Ernest Starling
,
.

, , :
) /
)
) .
.
, ,
, ,
.
,
,
. ,
, ( ,
-)
(signal transduction) . , , ,
.

2.

:
) (.. )
) (.. )
) (.. )
)

(.. ).
, ,
( ,
, , ,
, ,
). .2
.3 ""


.


-.

.
/
. ,
,
(cascade):
ng,
, g
(.3), ,

mg (.3)
(.3).

2
 ()
(. .26)

3. . () , ()
, ()

.3, , ,
,
. .1,
, .

3
 1.

/
--5--


( ) (41 ) ACTH
(CRF CRH ) -
(10 ) LH, FSH
(GnRF GnRH)

(PRF)
(40 44 ) GH
(GRH)
(SIF) (14 28 ) A GH ,TSH
(3 ) TSH, -
(TRH)

() (9 ) ,
(, ADH) (9 ) , 2
( 2 )
O SH (13 )
(MSH) SH (18 )
SH (12 )
(LPH) LPH (93 )
LPH (60 )
( (39 )
.,ACTH)
(GH) (191 ) ,
(197 )
(TSH) . 2 -
(:96, :112 .)
(LH) .2 . :
(:96, :121 ) :
(FSH) .2 . : , -
(:96,:120 ) ,
:

, (4, 3) I
(.3.2.2)
(32 ) Ca 2+, Pi

. () (37 ) Ca 2+, Pi
(.3.3)
(.. )

(.. )

() (. 3.2) ,
, , -
.
() , -

4
 /

( -) (2 21 ,,
30 ,.3.1.1)
( -) (29 ) ,

(36 ) ,

(14 ) -

() (- ,
,)
() -
()
, , -
.
() , -
() .
( ) 1 .(2 FSH
134,116 .)

,
2 LH
(:96,:147 .)
2
(22 32 .)

(17 ) ,

(, pH<4,5) (27 )
(, )
(CCK) (33 )
(14 )

(28 )
(VIP) ,
(GIP) (43 )

( - ,
(ANP) 126 .)

(8 .)

1,25- D3 Ca,

(167 )
( )
,
, .
-
( , ) ,
,
( .)
- -

- , -
(PAF) .

5
3.

3.1

3.1.1

.
, .
'
, ,
, ,
. , ,

-
- ( ),
20-30 , , . -
, () .
- (),
(signal-peptidase) -
(.. ) , ,
Golgi, .
, , , ,
(, ).
, ,
.
.4.

4.

6
 ,
. 1922 Banting Best

.

1955, Fred Sanger. H
, ,
(.5).
20 Steiner (, )
,

( C)
. mRNA
,
mRNA -
- (23 ),
. .5 ()
().

5. () . () .

7

mRNA .
, ,
. .

3.1.2

. (POMC),
8 (ACTH),
-, -, - (-,
) (.6). (
),
-, ,
- () -
(L). ()
(Arg-Lys, Lys-Arg, Lys-Lys) (.6).
-

,
. ,
,
.

6. ..

, ,
-, (
, ADH) -
(. 7). O ,
, . -
.
(barorecepors)
,

. , ,
( )
.

8
 7. .

3.1.3

, , , (-
-) - ()
(.6).
, TRH (Thyrotropin realeasing hormone,
) , TRH.
, ,
, Gln-His-Pro-Gly.
TRH
,
. TRH (.8).

8. TRH.

9
3.1.4

TRH (
) (.8)
.
. , GnRH RH
(.2).

2. .

3.1.5 ()

(TSH), (LH), (FSH)

o (hCG)
. (. .1)

3.2

3.2.1

,
. , ,
(, ) (DOPA)

.
( ). 9. , (
), 3,4- (DOPA),
. ,
,
.
cAMP ( ). To
, DOPA , DOPA-
,
L- L-

10
 , . -
(DBH) ,
.
-- (),

.
, S- S-
.

9. : . B:
.

( , chromaffin),
ATP 4:1 .
( )
(.9).
(stress)
.
, Ca2+
"" ATP .

(.3.3.1),
. ,
( M )
. 10 ,

, : CRH

11
 , ACTH
- .
(. 3.3), ,
,
(. 9). ,

(.. )
() . [
].

10. ,
. [ = --, =
, P = , CTH = ].

3.2.2

(4)
(3), .11,
() (DIT).
, ( 660 kDa), 75%
.



..
,
.


. (.12).

11. 4 3

12


12. : () ().
: 3 4
(=,TG=, L=, =)

3, 4
-
:
) 20% 140 o yr
3,5--
o- 4:1.
22.
-,
25:1,
+ (-2e) (-1e), .
.13. ,
,
, , .

13.
-22

13
 ) ( DIT DIT) ,
, 3 4.
,
.
)
. 3 4

SH (), (.12),
TBG (Thyroxine Binding Globulin)

.

.

3.3

3.3.1
C

(.14)
(1) ()
.
(2) ( )
.
(3) (),

(4) (, ),

.
(5) (, )
.
,
.
-
.

(. 14)
,
, ACTH ,
FSH, LH
.
,
.
-

( P450, . 3.3.2) (C-
20 C-22) ,
(.14 15).

14
 14.
.

(, ). () (CTH)
, (LH) (FSH) .
(.
14).
cAMP .
, ,
.
.
, (corticotrophin releasing hormone,
CRH, . 1), .
H CRH, , (ACTH) ,
, ,
(. .3).
, CRH ( ),
ACTH ( ) .
(feed back
control) (. . 7).

- (C27)
. 15.
(C21)

3- 4,5- (C21)

(C21), (C21) (C21),

15
 (C19) (C18). . 12,
C-21 ,
,
().
C-17 17-

15. .

16
.
(), .
17-
C-17 ,
.

3.3.2

.
,
(. . 27, 28).
,
( )

(, ).
(
)
.
.

:
,
, -1.6-, -6-





DNA

.

.
+, Cl-, HCO3- 2 .

,


.
.

.
, 17-

.

17
 21-

(
ACTH
CRH ), ACTH,

. .
, 5-
.

3.3.3
450.

450 ( , CO
450nm) .

2 CO
.
:

DPH + H+ + O2 + RH NADP+ + H2O + R-OH

R ()
(.. ), (..
) (.. ).


. .
1, , .

.

, 450
, ,
..


.
450-Fe3+ 450-Fe2+ ( NADPH),
.
()
.

. 16
P450. P450
2 .
FeO3+. H
H
, .
NADPH (
).

18
 16. 450 NADPH

450 , ,
NADPH NADPH--
, FAD.
, 450,
(.17)
( ).

NADPH ++ FAD Fe2+ Fe3+ R+O2

450
()

NADP+ FADH2 Fe3+ Fe2+ ROH+H2O

17. 450 .

19
 (
), DPH- P-450 (
FAD FMN ),
(R) , 2
2 o ( .
18).

P450

1 e-
R

P450

NADPH 450
FAD FMN
RO 2

ROH + H2O
2 e-

P450-R P450

O2

18. 450

3.3.4 D 1,25 - D3

1,25 (1,25(OH)2D3)
D3 , 7-,
. , 7-
.
D3
. , D3
(. 19).
25()D3, 1,25
()2D3. (),
,
. 1,25()2D3
, .

(.19).

20
 19. 1,25 - D3

3.4 .

.
.
(.. ).
.
,
.

3.4.1

, .
2
(, )

21
.
2 (PLA2),
o C (PLC)
, D (PLD)
PLA2 (. 20).
, ,
.
450.
. 21. ,
,

, (20:5) .

20. .

21. .

) . 22
G2 (PGG2)
(PG).
.
PGG2 PGH2 PG
(TX) 2 (PGI2).

22
 2 (PGH2) (.22),
()
.

(COX). COX COX-1

, COX-2
. COX-2
.
COX ( )
15--9,11 ,
. ( )
PGG 15-- , PGH2 (. 22).

22. PGH2.

PGH2 (. 23):
PGE ( ) PGH2 PGE2
PGH1 PGE1. PGF- ( )
PGH2 PGF2a. PG- ( ) PGH2
PGI2. , TXA- ( ) PGH2 TXA2.
PGH1 8,11,14-
, .

,
PG
: , (ther) F
(Fosfat ) .
, PGF2a

23
 - .
.

23. PGH2 .

) . ,
, , .
5-, 8-, 12- 15- . 5-
, (. 24). ,

- C5 5--
(5-HPETE).
( 4) 5-
4 (LTA4 ) .
( LTA4 ) LTA4 LTB4 LTC4
(-S-), LTC4.
-- (-) LTC4
LTD4 . LTD4 LTE4
.
LTC4, LTD4 LTE4 SRS-A (slow reacting substance of
anaphylaxis).
, -
() (. 24).

24
 24. ( ).

3.4.2

(platelet activating factor, PAF)

1- --2--sn-3- 1---
2--sn-3- (. 25).
2, 2-
1---2-- (-PAF). -
, ,
-2 PAF.
PAF
-PAF,
1---2--sn-3-
(. 25).

25
 25.
(PAF).

3.4.3.

-, (anandamide)
2-. CB1
CB2, , G, (.
.11) , (.
). ,
, .
2-
.

4.A

.
, ,
, -
Golgi .

. , ,
,
2, .
, ,
(.3.2.1), .

26
 ( 3.2.2)
. ,
. () .

,



















mRNA
mRNA

5.

H ,
, (.3). ,

( ) (, down stream)
. ,
.
. 26
.
(
, ),
(releasing hormone), ng.
, (.3), -
. ,

27
 g, ,
g mg . ,
(half- life). ,

1 .
,
. . 26,
,
( , . .7).

26.

, :
,
,
.
.

28
5.1 ,

. .
,
, . 24 (circadian)
/ .
:
ACTH (),
(~8:00) ,
.
TSH
( )

( )
-
. ,
, ,
.
28
-.

. 27.

27: . .

(. 28).

29
 28: .
(hCG).

6.

. , -
, 10-11-10-10 10-10-10-9 ,
.
5-100 5-10 .
(binding carrier)
. (.2). ,
, ,
.
.
(), -
.
,
, ().

"" (kd ~10-8-10-9 M).
G (Thyroxin binding globulin),
. ,
( 7).

.
(..G),

(S),
(),
. .
, 0,02-0,04% .
, :
)
)
)
) .

30
7.

(,
feedback control), .

, .

, ,
, ,
, .26,
( ).
( )
,
.
.

, . ,
,
,
(FSH) (LH). FSH
,
. , ,
()
.

(, ), ( )
.

(. . 26, 29).
LH , (corpus luteum)
(.29).


(. 27, 29).
(),

(CG),
( ).
, (. 27,
29).

31
 29. ( ) ( )
.

8.

(, half life)
(.3).
,
. , ..
R, GRH
(.2) ,
. ..
rg-
,
.

, TSH, LH, FSH, hCG,

, .
,
, .
.

, ,
.
(3.3.3),
, ,

32
 , ,
.
PAF ,
( 1 ),
,
. o LTB4 , LTC4 LTD4
LTE4 .

, 2-AG .

9.

,
, ,
,
.

: ( )

,
. (.27, 28,
29), , , .

,
, Langerhans
( - ).
( Gs
, .11)
, cAMP
(. ).
80-90mg/100mL.
(.. )
( stress
). , ,
( , .11),
, ,
.
.
~80mg/100mL (. 30).

33
 )
() ()

( ) ( )

- () -

cAMP,

) ()
: , ,
.
:


(internalization)
(down regulation)
: DNA, RNA, ,

30. ()
(). ().

:
.
(-),
(3.3.2).
.


,
.

10.

(signaling molecules),
,
, .

34
 (.8.1),
- .
.
. 30,
, (,,), (,) ,
(),
().
,
- ,
(.. , ).

31.
.

10.1

, :
(, binding) .
(receptors),
( , ), (,
), :
)

) (response).

,
. ,
, .

.

:
1) (specificity)

35
 2) (affinity)
.
(Kd)
3)
4) ,

5)
( , ),
Van der Waals .
,
,

.
, ,
(insuline like growth factor
I), .

, -

H+R HR
:

[ H ][ R] k 2
= = kd ( ) (1)
[ HR] k1
[] [R] ,
[HR] -.
kd, -,
(affinity) .
[R] = [HR] kd = [H]

( 50% ), kd. ,
, .
,
1/10 10 (kd).
(
), -
(.32) , 9-91%.

()

()

()

32. .

36

,
, Scatchard (Scatchard plot, 1947).
, ( [B]/[F],[F])

. , ,
Scatchard .

Rt = ,

[Rt] = [HR] + [R] [R] = [Rt] - [HR]

(1) HR (ound hormone)

F (Free hormone), ,

[ B] [ R]
= (2)
[ F ] Kd

[R] = [Rt] []

(2)
[ B ] [ Rt ] - [ B ] [ B] -1 [ Rt ]
= = +
[F ] Kd [ F ] Kd[ B ] Kd

kd Rt
(=-+) . 33.
, ( kd ),
( =-1/ kd) .
, , , [] / [F] 0
(.33) (capacity)
.

33. Scatchard .

To , . ,
. 32, ,
.

37
(non specific binding) .

(. 32).
,
( ) (
). ,
, .
, ,

. , ,
,
. , ,
, ,
. 32, ().

10.1.1

, ,
Scatchard 33.
. ,
,
.
Scatchard
.
.
Scatchard
,
.

10.1.2
.

%
.
,
.
. ,
.
. ,
,
.
, 10%
.
() (spare
[ H ][ R]
receptors). [ HR ] =
Kd
[]
[R] [R].
[R]
, .
,

38

.
/
.

10.1.3 .
.

( ) .
(up-regulation) (down-
regulation),
.
, ,

.
(down-regulation)
.
) . ,

.

, , ,
(EGF), (PDGF). -
, LDL ,
.
, ,
. ,

().
, .
EGF
(half life) 30min
,
EGF.
) . ,
,

.
,
cAMP,
,
.

39
11.

.15 Stryer (4 ,
)
. ,
.

i) G ( 7 , 7 )
:
(AC): ( Gs)
( Gi) AMP (cAMP) ( ,
second messenger). ().
C (PLC): 4,5-
(2), (DAG, ) 1,4,5-
(3, ). DAG
C (PKC), 3 Ca++
.
Ca++ .

2 (PL2): ,
, ( )
-.
D (PLD), G:
( ), (
), ( ).

ii) (GC),
GMP (cGMP, ).

( ) cGMP.

iii) (RTK,
receptor tyrosine kinase). :
(1) RTK (..
).
(2)
(- cross-phosphorylation) RTK
(.. ).
(3) JAK (Janus kinase)
RTK (..
, )

(.. , )
,
(nuclear hormone receptors). -
DNA (control elements) .

40


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the Cell, 4th edition, Garland Science
Berg J.M., Tymoczko J.L. Stryer L. (2004) , 5 ,

Berg J.M., Tymoczko J.L., Stryer L. (2006) Biochemistry, 6th edition
Burtis C., Ashwood E., (2001) Tietz Fundamentals of Clinical Chemistry, 5th edition,
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Cooper J.R., Bloom F.E., Roth R.H. (1996) The Biochemical Basis of
Neuropharmacology, 7th edition, Oxford University Press
Delvin T.M., ed (1992) Textbook of Biochemistry with Clinical Correlations, 3rd
edition, Wiley-Lis
Garett R.H, Grisham C.M. (2005) Biochemistry, 3rd edition
Gurr M.I., Harwood J.L., Frayn K.N. (2002) Lipid Biochemistry An Introduction, 5th
edition, Blackwell Publishing
Lodish H., Baltimore D., Berk A., Zipursky S., Matsudaira P., Darnell J. (1999)
Molecular Cell Biology, 4th edition, Freeman
Mathews C.K., van Holde K.E., Ahern K.G. (2000) Biochemistry, 3rd edition,
Addison Wesley Longman
Zubay G., (1993) Biochemistry, 3rd edition, Wm.C.Brown Publishers

41