T E M A 12 :

-AMINOACIZII PROTEINOGENI.
PEPTIDELE.

Formula general a -aminoacizilor

R CH COOH

H2N CH COOH

NH2

Stereoizomeria -aminoacizilor

COOH
H2N

H
R

L--aminoacid

COOH
H

NH2
R

D--aminoacid

Proprietile acido-bazice i structura bipolar

a -aminoacizilor. Punctul izoelectric.
+HCl
CH3

CH COOH
NH2
Alanina

CH3

CH COOH
NH3+ Cl-

Clorura de alanina

+NaOH
CH3
-H2 O

CH COONa
NH2

Sarea de sodiu a alaninei

Echilibrul ionic al -aminoacizilor n soluie

H2 N CH COOH
R
+
+
+H
H3 N CH COOH

Form cationic
n mediul acid

+
+HO
H3N CH COOH2N CH COOR
R

Ion bipolar
(amfiion)

Form anionic
n mediul bazic

Clasificarea -aminoacizilor
I. -Aminoacizii alifatici monoaminomonocarboxilici

CH2

COOH

NH2

Glicin (Gli)
acid -aminoacetic
(2-aminoetanoic)
CH3

CH CH COOH

CH3 NH2
Valin (Val)*
Acid -aminoizovalerianic
(2-amino-3-metilbutanoic)

CH CH COOH

CH3

CH2

CH3 NH2

CH3

CH COOH
NH2

-Alanin (Ala)
acid -aminopropionic
(2-aminopropanoic)
CH3

CH CH2

CH COOH

CH3
NH2
Leucin (Leu)*
Acid -aminoizocapronic
(2-amino-4-metilpentanoic)

Izoleucin (Ile)*
Acid-amino--metilvalerianic
(2-amino-3-metilpentanoic)

II. -Aminoacizii hidroxilici (alifatici, neutri, polari)

CH2

CH COOH

OH

NH2

Serin (Ser)
Acid -amino--hidroxipropionic
(2-amino-3-hidroxipropanoic)

CH3

CH CH COOH
OH NH2

Treonin (Tre)*
Acid -amino--hidroxibutiric
(2-amino-3-hidroxibutanoic)

III. Tio--aminoacizii (mercapto--aminoacizii)

CH2

CH COOH

CH2

SH

NH2

SCH3

Cistein (Cis)
Acid -amino--tiopropionic
(2-amino-3-tiopropanoic)

CH2

CH COOH
NH2

Metionin (Met)*
Acid -amino--metiltiobutiric
(2-amino-4-metiltiobutanoic)

IV.-Aminoacizii monoaminodicarboxilici
HOOC CH2

CH COOH

HOOC CH2

CH2

NH2

NH2

Acid asparagic (Asp)

Acid -aminosuccinic
(2-aminobutandioic)
O
H2N

C CH2

CH COOH
NH2

Asparagin (Asn)
Amida acidului asparagic

CH COOH

Acid glutamic (Glu)

Acid -aminoglutaric
(2-aminopentandioic)
O
H2N

C CH2

CH2

CH COOH
NH2

Glutamin (Gln)
Amida acidului glutamic

V. -Aminoacizii diaminomonocarboxilici

CH2
NH2

(CH2)3

CH COOH
NH2

H2N C NH
NH

(CH2)3

CH COOH
NH2

Lizin (Liz)*
Arginin (Arg)*
Acid ,-diaminocapronic Acid -amino--guanidinovalerianic
(2,6-diaminohexanoic)
(2-amino-5-guanidinopentanoic)

V. -Aminoacizii aromatici
CH2

CH COOH
NH2

HO

CH2

CH COOH
NH2

Fenilalanin (Fen)*
Tirozin (Tir)
Acid -amino--fenilpropionic Acid -amino--hidroxifenil propionic
(2-amino-3-fenilpropanoic)
(2-amino-3(p-hidroxifenil propanoic)

VII. -Aminoacizii heterociclici

CH2

CH COOH
NH2

N
H

N
CH2
N
H

CH COOH
NH2

Triptofan (Tri)*
Histidin (His)*
Acid -amino--(-indolil)Acid -amino--imidazolilpropionic
propionic
(2-amino-3-indolilpropanoic) (2-amino-3-imidazolilpropanoic)

Iminoacizii heterociclici:
HOHO
N

COOH
COOH
N
H H

Prolin (Pro)
Acid -pirolidin-carboxilic
(2-pirolidincarboxilic)

COOH
COOH

N N
H H

Hidroxiprolin
Acid 4-hidroxi-2-pirolidincarboxilic

Proprietile chimice ale -aminoacizilor

1. Formarea esterilor
O
H2 N CH C
R

OH

+ HO C2 H5

(HCl)

+ H2 O
H2 N CH C OC H
2 5
R
Ester etilic

2. Formarea srurilor complexe

CH3
2 CH3

CH COOH
NH2

Alanina

+ Cu(OH)2

-2H2O

CH NH2

C O

Cu
O C

H2N CH CH3

Dialaninat de cupru

3. Interaciunea -aminoacizilor cu acidul azotos

(reacia de dezaminare in vitro)
R CH COOH + HNO2
NH2

-Aminoacid

R CH COOH + N + H O
2
2
OH

-Hidroxiacid

4. Interaciunea -aminoacizilor cu aldehida formic .

O
R CH COOH + H C
H
NH2
-Aminoacid

R CH COOH
N CH2

+ H2O

Acid metileniminocarboxilic

5. Reacia de alchilare a -aminoacizilor

CH3

Cl + H2N CH2

Clorura de metil

COOH

-HCl

CH3

Glicin

HN CH2

COOH

N-metilglicin

6. Reacia de acilare a -aminoacizilor.

O

O
CH3

C Cl + H2N CH2

Clorur de acetil

COOH

Glicin

CH3

C NH

CH2

COOH

N-acetilglicin

7. Interaciunea -aminoacizilor cu fenilizotiocianat

(reacia lui Edman).
O

S
C6 H5

N C + H 2N

Fenilizotiocianat

CH

S
OH

C6 H5

NH

O
NH

C6 H5

N
O C

OH

Produs de aditie nucleofila

S

+H
-H2 O

CH

NH
CH R

Feniltiohidantoina
FTH

Reaciile -aminoacizilor cu importan biologic.

1. Transaminarea -aminoacizilor
COOH

COOH
CH

NH2 + C

piridoxalfosfat
transaminaza

R2

R1

-aminoacid 1 -oxoacid 2
H

HO
H3 C

C
R1

COOH

CH
R2

NH2

-aminoacid 2 -oxoacid1

O
CH2OPO3H2

COOH

coenzima
Piridoxalfosfat

De exemplu, obinerea acidului asparagic i acidului

-ceto-glutaric prin interaciunea acidului glutamic i oxalilacetic

HOOC CH2 CH2 CH COOH

acidului glutamic

NH2

HOOC CH2 CH2 C

O
-ceto-glutaric

HOOC CH2 C COOH

Transaminaza
Piridoxalfosfat

COOH

HOOC CH2 CH COOH

NH2

Mecanismul trancaminrii
O

H
2OCH2OPO3

HO

H2N CH COOH

H 3C

CH2 CH2 COOH

N
H

Piridoxalfosfat

Acidul glutamic
CH2NH2

HO

OCH2OPO3
+

H3 C

2-

O CH COOH
CH2 CH2 COOH

Piridoxaminfosfat

Acidul 2-oxoglutaric

CH2NH2

2OCH2OPO3

HO

H 3C

O CH COOH

CH2 COOH

Piridoxaminofosfat
O

Acidul oxalilacxetic
H
2OCH2OPO3

HO

+
+

H 3C

H2N CH COOH
CH2 COOH

N
H

Piridoxalfosfat

Acidul asparagic

2. Dezaminarea oxidativ.

HOOC CH2

CH2

Acid glutamic

CH COOH + NAD+
NH2

HOOC CH2

CH2

Acid -iminoglutaric

HOOC CH2
HOOC

CH2

C COOH + NADH + H+
NH

COO H + H2 O

NH
CH2 CH2

Acid -cetoglutaric

C
O

COO H + NH3

3. Decarboxilarea -aminoacizilor

R CH COOH

decarboxilaza
piridoxalfosfat

NH2

CH

OH
NH2
Serina

COOH

NH2 + CO2

Amina biogena

-Aminoacid

CH2

R CH2

decarboxilaza
piridoxalfosfat

CH2

CH2

OH
NH2
Colamina

+ CO 2

4. Hidroxilarea -aminoacizilor

CH2

CH COOH
NH 2

Fenilalanina

hidroxilare
Fenilalaninhidroxilaza

HO

CH2

Tirozina

CH COOH
NH 2

Peptidele.
De exemplu, la condensarea -alaninei cu glicina i valina
se obine tripeptidul alaninil-glicil-valin
O

H2N CH C OH

H NH CH2

C OH

H NH CH C OH

CH3

CH(CH3)2
O

O
H2N CH C

NH CH2

CH3

Ala-Gli-Val

O
NH CH C OH
CH(CH3)2

-2 H O
2

Structura legturii peptidice

Hidroliza peptidelor:

H2N

CH C

NH CH C

R1

O
NH CH C OH
R3

R2
CH C OH
R1

O
H 2N

H2O (H+)

H 2N

CH C OH
R2

H 2N

CH C OH
R3

De exemplu, determinarea acidului N-terminal prin metoda Edman:

O

S
C6H5

N C

H2N CH C NH CH C NH CH C OH
CH(CH3)2

CH3

Fenilizotiocianat

Ala - Val - Gli

S
C6H5

NH C NH

CH C NH CH C NH CH C OH
CH3

CH(CH3)2

S
C
C 6H 5
O

N
C

O
NH
CH

FTH alanina

CH3

H2N CH C NH CH C OH
CH(CH3)2
Val - Gli

Sinteza chimic a peptidelor

O
H2N CH C
CH3
Ala

Ala - Ser

O
+

H2N CH C

OH

CH2OH
Ser

Ser - Ala

OH

Ala - Ala
Ser - Ser

1. Blocarea aminogrupei n alanin:

(CH3CO)2O +

O
H2N CH C
CH3

OH

CH3

C NH CH C
CH3

OH

+ CH3COOH

2. Activarea grupei carboxil n alanin:

O

O
C6H5

CH2

NH CH C
CH3
O

C6H5

CH2

O
OH

+ Cl

C O C2H5

Etilclorformiat

-HCl

NH CH C O C

C2H5

CH3
3. Protejarea grupei carboxil n serin:
O

O
H2N CH C
CH2OH

OH

+ C 2H5OH

H2N CH C O C 2H5 + H2O

CH2OH

4. Formarea legturii peptidice:

O
CH3

2H 5

C NH CH C O C C2H5 + H2N CH C O C2H5

CH3

CH2OH

O
CH3

C NH CH C

NH CH C O C2H5

CH3

+ C2H5OH + CO2

CH2OH

5. Deblocarea grupelor funcionale:

O
CH3

C NH CH C

NH CH C O C2H5

CH3
H 2O

H 2N

CH

O
H2O

H2N CH C
CH3

CH2OH

NH C H C

CH 3

C H2 OH
Ala - Ser

A
OH

CH3COOH

C2H5OH

Dipeptide:
O
H2N CH2

CH2

C NH CH COOH
CH2
H N

Carnozina
-Alanil-L-Histidina

O
H2N CH2

CH2

C NH CH COOH
CH2
H3C N

Anserina
-Alanil-N-metil-L-Histidina

Tripeptide

H2N

CH

CH2 CH2 C

COOH

O
NH

CH

NH

CH2 COOH

CH2SH
- (-Glu-Cys-Gly)
Glutation

-Glutamilcisteinglicina (-Glu-Cys-Glu)

Glu
2 Glu

Cys

Gly

-2H

+2H

S
Glu

Forma
redus, GSL

, GSH

Cys

Cys

Gly

Gly

Forma
oxidat, GSSG

, GSSG

H3N

Cys

Tyr

Hormoni peptidici
3

Ile
H3N

Cys

Tyr

Phe

Cys

Asn

Gln

Gly (CONH2)

Cys

Asn

Gln

Pro

Leu

Pro

Arg

Gly (CONH2)

Oxitocina

Vasopresina

Insulina
259377N65O75S6
F. Senger (1943 .)
Mr=5727