CHUYEN HOA PROTEIN VA ACID AMIN

MUC TIEU
1. Trnh bay c cac enzym thuy phan protein va c che tac
ong cua chung.
2. Viet c cac phan ng kh amin, kh carboxyl, trao oi amin
cua cac acid amin cung cac c che cua chung.
3. Mo ta c cac giai oan cua chu trnh ure.
4. Mo ta c s bien hoa cua acid -cetonic.
5. Trnh bay c s thoai hoa rieng biet cua cac acid amin.
6. Trnh bay c nguyen tac chung e tong hp acid amin.
7. Trnh bay c cac yeu to va thanh phan tham gia vao qua
trnh sinh tong hp protein.
8. Mo ta c ba giai oan cua s sinh tong hp protein ribosom.
1-BIEN HOA PROTEIN
1.1- Tieu hoa protein- Cac enzym thuy phan protein
1.1.1-Endopeptidase
1.1.2- Exopeptidase
PEPTID
PROTEIN


ACID AMIN


CO
2
, H
2
O URE, Q San pham sinh hoc
ac biet
Tieu hoa
Hap thu
PROTEIN
(cac to chc)
Ong tieu hoa
Te bao
NH
2
CH
R1
NH
CH
R'
CO
NH
CH
R''
CO
CH
Rn
COOH
au N tan
au C tan
Peptidase
OH
H
H
2
N COOH
aa N tan aa C tan
Pepsin
(da day)
Trypsin
(tuy tang)
Chymotrypsin
(tuy tang)
pH=1,7-2 pH=8 pH=8
a b c d e f
a : Glu
b : Tyr, Phe (-NH
2
)
(Leu-Val,Leu-Glu)
c : aa kiem (Arg, Lys) (-
COOH)
e : Tyr-CO-NH
(Phe,Try,Met,Leu)
Cac Endopeptidase
H
2
N COOH
aa N tan aa C tan
OH
-
OH
-
Aminopeptidase
(TB ruot non)
Carboxypeptidase
(tuy tang)
Dipeptidase
(TB ruot non)
OH
-
H
2
N COOH
Cac Exopeptidase
1.1.3- Enzym thuy phan protein cac to chc
- Co cac Catepsin : A,B,C
- Carboxypeptidase va Aminopeptidase
- Cac enzym c cha trong cac lysosome
S co mat cua cac enzym nay giai thch hien tng t tieu cua
te bao khi te bao chet
1.2- Can bang ong cua protein
Nit trong c the lien tuc chuyen hoa nhng van am bao s
can bang am
Can bang am
Nit nhap = Nit xuat
Nit nhap > Nit xuat
Nit nhap < Nit xuat



(+)
(-)
(+) : c the ang ln, co thai, dng benh
(-) : oi an, sot, sau khi mo
Cac trng hp benh ly:
Giam Protein/huyet thanh
do giam nhap hoac giam san xuat
do tang mc phan huy
do mat protein
do loang mau
Tang protein/huyet thanh
do mau co ac
xuat hien protein bat thng
suy vo thng than (Addison)


1.3- D tr protein
- Gan
- Huyet tng
- C (cung cap protein cho nao va tim)
D tr long leo
2- THOAI HOA ACID AMIN
2.1- Nhng qua trnh chung cua s thoai hoa acid amin
2.1.1- Kh amin
- Phong thch Nit di dang NH
3
- 4 con ng kh amin
2.1.1.1- Kh amin - kh oxy

R CH
2
COOH
R CH
2
CH
NH
2
COOH
+2H
+
-NH
3
2.1.1.2- Kh amin noi phan t
R CH
CH
COOH
-NH
3
Acid tng ng
Acid khong no tng
ng
2.1.1.3- Kh amin thuy phan

R CH
COOH
OH
R CH
COOH
NH
2
+H
2
O
-NH
3
Oxy acid
2.1.1.4- Kh amin oxy hoa

+1/2 O
2
-NH
3
Acid -cetonic
C che: 2 giai oan
G1: Kh hydro

R C
COOH
NH
Dehydrogenase
FAD FADH
2
G2: Thuy phan t phat
R C
COOH
NH
R CO
COOH
-NH
3
+H
2
O
Acid imin
Acid -cetonic
Qua trnh kh amin cua aa c the ong vat bao gi cung la
qua trnh kh amin-oxy hoa
-2H
oi vi acid glutamic
COOH
CH
2
CH
2
CH
COOH
N H
2
COOH
CH
2
CH
2
C
COOH
N H
COOH
CH
2
CH
2
C
COOH
O
L-Glutamat dehydrogenase
NAD
+
NADH+H
+
NADPH+H
+
NADP
+
H
2
O NH
3

L-glutamic acid
Acid -cetoglutaric
+ Phan ng thuan nghch
+ Chieu ngc lai : amin hoa-kh oxy
Amin hoa-kh oxy : co nh NH
3
vao hp chat hu c (-ceto
glutaric thanh a. glutamic)
nhom amin de dang chuyen sang a. -cetonic khac nh
phan ng chuyen amin

Glutamat dehydrogenase:
- ong vat cao cap :
+ gi vai tro thoai dng (kh amin-oxy hoa) vi coenzym la NAD
+ ket hp vi cac transaminase e thoai dng cac aa
+ NH
3
tao ra c dung lam nguyen lieu tong hp ure
- vi sinh vat :
+ tac dung theo hng sinh tong hp (amin hoa-kh oxy) vi coenzym
kh la NADPH

COOH
CH
2
CH
2
CH
COOH
N H
2
CH
3
CO
COOH
COOH
CH
N H
2
CH
3
COOH
CH
2
CH
2
C
COOH
O
2.1.2- Phan ng trao oi amin
Braustein va Krisman (1937) (n/cu c)
+ +
Glu a. Pyruvic
a. -cetoglutaric
Ala
COOH
CH
2
CH
2
CH
COOH
N H
2
N CH
3
OH
POH
2
C
CHO COOH
CH
2
CH
2
C
COOH
O
N CH
3
OH
POH
2
C
CH
2
-NH
2
C che : 2 g
-Giai oan 1
+ +
Glu Pyridoxal P Pyridoxamin P
a. -cetoglutaric
N CH
3
OH
POH
2
C
CH
2
-NH
2
CH
3
CO
COOH
N CH
3
OH
POH
2
C
CHO
COOH
CH
N H
2
CH
3
- Giai oan 2

+ +
a. pyruvic Alanin
Transaminase : co c, gan, than, tim, ruot
Hai loai pho bien va hoat ong manh
+ glutamic oxaloacetic transaminase (GOT)
= Aspartic transaminase (ASAT)
Glu + a. oxaloacetic a. -cetoglutaric + a. aspartic

+ glutamic pyruvic transaminase (GPT)
= Alanin transaminase (ALAT)
Glu + a. pyruvic a. -cetoglutaric + Alanin
GOT
GPT
Gia tr bnh thng trong huyet thanh :
GOT t 15 29 U/l
GPT t 11 26 U/l
-Viem gan cap tnh : tang GOT, nhng chu yeu tang GPT (co khi
gap 100 lan) ngay ca trc khi xuat hien vang da co
gia tr dch te hoc
- S tang GPT cho thay mot tac ong phan huy cua te bao gan
-Viem gan man : transaminase tang t, bieu th s ton thng nhu mo
gan do hoai t te bao gan
Nhoi mau c tim :
+ tang rat cao GOT, GPT tang t hn
+ Khi nhoi mau c tim, GOT bat au tang t gi th 6 tr i.
keo dai cho en gi th 36 va tr ve bnh thng sau 5 6
ngay
+ Ty so De Ritis = GOT/GPT > 1
+ s gia tang cua ca GOT va GPT cho mot ch so ve o ton
thng cua gan co the keo ngay sau suy tim do nhoi mau
GOT cung tang trong nghen mach phoi, nhoi mau than
S lien quan gia phan ng trao oi amin va s kh amin-oxy hoa
- Cac aa eu co the trao oi amin c, manh nhat la Glu, Asp, Ala
- Nhieu enzym kh amin-oxy hoa cua cac aa th hoat ong yeu tr
Glutamat dehydrogenase
- Cac transaminase th hoat ong manh va pho bien

Phan ln aa kh amin-oxy hoa gian tiep qua cac
transaminase cung vi a. -cetoglutaric va glutamat
dehydrogenase
R CH
COOH
NH
2
a.-cetoglutaric
R CO
COOH
a.Glutamic
NH
3
Transaminase
Glutamat dehydrogenase
1
2
- Kh amin cua tat ca cac acid amin
- Tong hp mot so acid amin (Glu, Asp, Ala) (do trao oi
amin)
2.1.3- Kh carboxyl
- Kha pho bien ong vat
- Pho bien VSV

R CH
COOH
NH
2
+ CO
2
Descarboxylase (vit B6)
R CH
2
NH
2
R- CHO + NH
3
O
2
mono amino oxydase
diamino oxydase
Histidin Histamin
Gian mach, co c trn, tang tnh tham thanh mach

Glutamc acid -amino butyrat
(GABA)
GABA : - ieu hoat hoat ong than kinh
- c che phan xa than kinh
Histidin descarboxylase
Glutamat descarboxylase
Thiosemicarbazid
Hydrazid
INH
c che glutamat decarboxylase
Giam GABA, gay co giat
Reserpin giam lng GABA/ TKT

ngng kch thch cua te bao than kinh vi
soc ien
2.2- San pham cuoi cung cua s bien hoa acid amin
2.2.1- Chuyen hoa cua NH
3
2.2.1.1-S tao thanh Glutamin
CO-NH
2
CH
2
CH
2
CH
COOH
N H
2
COOH
CH
2
CH
2
CH
COOH
N H
2
+ NH
3
+ H
2
O

Glutamin synthetase
ATP
Glutaminase
Glutamic acid
Glutamin
- Dang van chuyen khong oc cua NH3
- 60-100mg/l mau
- Co hau het cac to chc
Glutamin
ATP
Pi + ADP
NH
3
a. Glutamic
Glutamat synthetase
Glutamin
Glutamin
Glutamin Glutamin
THAN GAN
NH
3
NH
3
(ca)

NH
4
+
NH
4
+
URE (a. uric:
chim, bo sat)
URE
NC TIEU
MAU
MO
H
2
O
Glutamat
H
2
O
Glutaminase
2.2.1.2. S tao thanh ure (chu trnh Ornitin cua Krebs va Henseleit:
Mau tnh mach ca en gan cha nhieu NH
3
hn
mau gan ra.
Nong o ure cua mau gan ra cao hn mau ti
gan.
ong vat a cat gan, nong o ure trong mau ha.
Trong 1 so trng hp benh ve gan nh x gan, [NH
3
] trong
mau cao.
Gan la ni san xuat ure t nhng goc NH
3
.

Krebs va Henseleit a chng minh bang thc nghiem s tao
thanh ure

Sau o Ratner va Cohen a xac nh chi tiet cac phan
ng enzym cua qua trnh tong hp ure.

Giai oan 1: Chuyen ORNITIN thanh CITRULIN
Gom 2 bc:
- Bc 1: Tao thanh carbamyl phosphat khong ben.



Glutamat Glutamin
NH
3
+ CO
2
2ATP
2ADP + Pi
H
2
O, Mg
++
N-acetylglutamat
Carbamyl phosphat
synthetase
H
2
N-C-O ~ PO
3
H
2
O
carbamyl phosphat
Xay ra trong ty the
TB gan
- Bc 2 : chuyen nhom Carbamyl P ti Ornitin e tao thanh
Citrulin
COOH
|
NH CH
|
) (CH
|
NH CH
2
2 2
2 2

2 3
2
H PO ~ O
|
O C
|
NH

COOH
|
NH CH
|
) (CH
|
PO H CH
|
NH
|
O C
|
NH
2
2 2
4 3 2
2

+
OCT
OCT = Ornitin carbamyl transferase
Ornitin Carbamyl P
Citrulin
Xay ra trong ty the
TB gan
Giai oan 2: chuyen CITRULIN thanh ARGININ
COOH
|
NH CH
|
) (CH
|
NH
|
CO
|
NH
2
3 2
2

COOH
|
CH
|
CH N H
|
COOH
2
2

COOH
|
CH
|
CH
|
COOH
COOH
|
NH CH
|
) (CH
|
NH
|
NH C
||
NH
2
2
3 2

+
ATP AMP+ PPi
Mg
++
,enzym

-H
2
O
Citrulin
Aspartat
Arginosuccinat
Enzym : Argino succinat synthetase


PPi 2H
3
PO
4
Pyrophosphatase
Bc 1: ket hp citrulin vi a. aspartic

tao

thanh Arginosuccinic
Bc 2: tach Arginosuccinic thanh Arginin va acid fumaric
NH COOH

C NH CH

NH CH
2


(CH
2
)
3
COOH

CH NH
2


COOH
NH

C NH
2


NH

(CH
2
)
3

CH NH
2

COOH
COOH
|
CH
| |
CH
|
COOH
+
Arginosuccinat lyase
Arginosuccinat Arginin
Fumarat
Fumarat Malat Oxaloacetat

Aspartat
Trao oi amin (Glu)
Giai oan 2 xay ra
gan va than
Giai oan 3: Thuy phan Arginin
COOH
|
NH CH
|
) (CH
|
NH
|
NH - C
| |
NH
2
3 2
2

COOH
|
NH CH
|
) CH (
|
NH CH
NH
NH
\
/
C O
2
2 2
2 2
2
2

Arginase
+H
2
O
Arginin
Ornitin
Ure
2NH
3
+ CO
2
+ 3ATP + 2H
2
O Ure + 2ADP + AMP + 4Pi
Pi Citrulin
Ornitin
Carbamyl Phosphat
2ADP + Pi
Enzym
NH
3
+CO
2
+H
2
O+ 2ATP
Citrulin
He thong van chuyen
Ornitin ac hieu mang
a. arginosuccinic
a. fumaric
a. malic
Arginin
Ornitin
URE
H
2
O
a. aspartic
ATP
AMP + PPi
a. oxaloacetic
Glu
-cetoglutaric
transaminase
Ty the Te bao chat
Ure huyet
Tang - viem than kinh nien ( 3g/l)
- viem than cap ( 5g/l)
- tieu chay, dch ta, choang (do mat nc)

Giam - cac benh ve gan (gan thoai hoa m, x gan, ung
th giai oan cuoi)
Ure/ nc tieu
-Trang thai sinh ly : oi vi phu n co thai
-Tuoi : tre em bai tiet > ngi ln tnh theo mmol
ure/24h/kg can nang)
- Benh ly : bai tiet / ai thao ng, sot ( thoai
hoa protid)
2.2.2. Bien hoa cua a. cetonic
Thoai hoa thanh cac chat trung gian /chu trnh a. citric
CO
2
va H
2
O.
Chuyen hoa tr lai thanh acid amin (trao oi amin hoac amin
hoa)
Tao thanh glucid:
cac cetonic acid a. pyruvic
-ceto glutaric
succinyl CoA
a.oxaloacetic
Tong hp
glucose hay
glycogen (gan)
Theo con ng cua cac acid beo sau khi kh carboxyl
Acetyl CoA tong hp cac acid beo
tao thanh cac chat cetonic
(cac acid amin tao ceton)
Va tao ng va tao ceton (va tao oxaloacetat va tao
acetyl CoA: Phenylalanin, Tyrosin, Tryptophan, Isoleucin va
Lycin)

-cetoglutarat
Succinyl CoA
Fumarat Oxaloacetat
Ile
Met
Val
Citrat
Arg
His
Gln
Pro
Glutamat
Tyr
Phe
Asn Aspartat
Leu, Lys,Phe,
Trp, Tyr

Acetoacetyl-CoA
Acetyl CoA
Ile
Leu
Trp
Pyruvat
Ala
Cys
Gly
Hyp
Ser
Thr
Chu trnh acid citric
S thoai hoa cua sn carbon cua cac acid amin.
2.3. Thoai hoa rieng biet cua cac acid amin
2.3.1. Cac acid amin tao oxaloacetat
Aspartat va Asparagin
2.3.2.Cac acid amin tao pyruvat
Threonin, Alanin, Cystein
2.3.3. Cac acid amin tao succinyl CoA: (cung co the tao
glucid)
Met, Val, Ile, Leu
2.3.4. Cac acid amin tao cetoglutarat
Glu, Gln, His, Pro, Arg

2.3.5. Cac acid amin tao Acety CoA
Thr, Gly, Ser, Ala, Cys, Phe, Tyr, Trp, Lys, Leu

Cystein
-Tao Taurin
- Tao pyruvat va SO
2
Taurin + acid mat Muoi mat
SO
2
SO
4

2-
[O]
Tao lien ket ester sulfat lien hp sulfat (c che giai
oc gan)
Methionin
Met + Adenosin S. Adenosyl Met

S. Adenosyl homo cystein

Homocystein

Cystathionin

Succinyl CoA
ATP
-CH
3
H
2
O

Adenosin

Ser
H
2
O

Cystathionin synthetase
Cystein (tao aa)
(Cung cap CH3)
Homocystein Methionin
CH
3
5 metyl tetrahydrofolat
Vit B12

Homocystein nieu:
Homocystein

Cystathionin
Cystathionin synthetase

Xuat hien Homocystein trong nc tieu 9tre3 b an on)
ieu tr sm:
-Vitamin B6 lieu cao
- Tang Cystein (do thieu Cys), giam Methionin
Phenylalanin va Tyrosin

Phe Tyr a.parahydroxyphenyl
pyruvic
Phe hydroxylase
Tyr transaminase
O
H
2
O
FH
4
FH
2
NADP
NADPH+H
NH
3
Quinol
Oxydase (Cu
++
)
Chuyen v
Nhom quinon
a. 2,5-di hydroxy phenyl
pyruvic
CO
2
[O]

a. homogentisic
= Alcapton
Oxydase (Fe
++
)
a. Maleyl acetoacetic
Glutathion kh
a.fumaryl
acetoacetic (enol)
ceton
a. acetoacetic
a. fumaric
1
2
3

a. acetoacetic


a. fumaric
Acetyl CoA
Acetat
cetothiolase
CoASH
Krebs
Phenyl ceton nieu (thieu Phe hydroxylase)

Tyr
NH
3
a. Phenyl pyruvic
a. Phenyl lactic
a. Phenyl acetic
Phenyl acetyl glutamin
Glutamin
2H

CO
2
[O]

Phe
- Phe va cac chat thoai hoa xuat hien trong nc tieu
-Tre an on, ieu tr sm bang che o an giam
Phe
-Cung lam thieu Tyr nen thieu Melanin
Thieu enzym oxydase: Tyrosin nieu
Acid para hydroxy phenyl pyruvic
acid homogentisic

- p-hydroxy phenyl pyruvat va tyrosin b ong trong mau va bai
xuat nhieu trong nc tieu.
- S dung vitamin C co the a s chuyen hoa tr lai bnh thng.

Thieu acid homogentisic oxydase benh Alcapton nieu.
- Benh bam sinh do thieu enzym oxy hoa acid
homogentisic lam acid nay khong thoai hoa c,
ong lai va ao thai ra nc tieu.
-Khi tiep xuc vi khong kh se b oxy hoa cho 1 sac
to mau nau de nhan biet.
- ngi bnh thng, acid homogentisic b oxy hoa
ngay khi tao thanh cho acid acetyl acetic va khong xuat
hien trong nc tieu.
S thanh lap Melanin
Phe Tyr DOPA
Tyrosinase
Dopaquinon
2-carboxyl-2,3-dihydro indol 5,6-quinon
Indol-5,6-quinon
Melanin
Polymer hoa
- Tao hormon giap trang
- Tao cac Catecholamin
S tao thanh creatin
Glycin+ Arginin Ornitin + Acid guanido acetic
Acid guanido acetic Homocystein + Creatin
Met
-Tao creatin phosphat khi tac dung vi ATP
-Sp kh nc la creatinin co trong c va ao thai qua nc tieu
S tao thanh glutathion

Glutamat + Cystein -Glutamyl cystein

-Glutamyl cystein + Glycin Glutathion
Glutathion ong vai tro cua 1 he thong oxy hoa kh (van chuyen
hydro).

Gan

ATP ADP + Pi
Gan
ATP ADP + Pi
3. TONG HP ACID AMIN
-Thc vat :
t NH
3
, NO
2
-
, NO
3
-

t N
2
(TV ho au)
- Vi sinh vat :
t NH
3
, NO
2
-
, NO
3
-
t aa can thiet
- ong vat cao cap :
- aa can thiet (8aa) (Rose va cong s)
- aa ban can thiet (Arg, His)
Acid amin can thiet Acid amin khong can thiet
Lysin
Threonin
Methionin
Valin
Leucin
Isoleucin
Phenylalanin
Tryptophan
Arginin (ban can thiet)
Histidin (ban can thiet)
Glycin
Alanin
Cystein
Acid glutamic
Glutamin
Acid aspartic
Asparagin
Tyrosin
Prolin
Serin
Nguyen tac chung :
Acid -cetonic acid amin tng ng
Amin hoa
NH
3
+ - cetoglutarat L-glutamat

Chuyen amin
a. Pyruvic + Glu Ala + - cetoglutarat
NADPH
2
NADP +H
2
O

GPT

Acid amin can thiet : acid amin ma c the khong the tong hp c
cac a. -cetonic cua chung
Glycin : c tong hp t CO
2
va NH
3
.
Alanin: c tong hp t pyruvat nh phan ng chuyen amin t glutamat
Cystein: c tong hp t Met qua nhieu giai oan
Acid glutamic: c tong hp nh phan ng amin hoa -cetoglutarat.
Glutamin: c tong hp t glutamat vaNH
3
, xuc tac bi glutamat synthetase.
Acid aspartic: c tong hp t oxaloacetat nh phan ng chuyen amin t glutamat
Asparagin: c tong hp t aspartat vaNH
3
, xuc tac bi asparagin synthetase.
Tyrosin: c tong hp t phan ng hydroxyl hoa phenylalanin.
Prolin: c tong hp t glutamat .
Serin: c tong hp t glycin hoac t 3-phosphoglycerat.