Documente Academic
Documente Profesional
Documente Cultură
proteinelor
Proteine
endogene
Proteoliz
Proteine Absorbtie
exogene intestinal
Porfirine
Proteosintez
Catabolismul
aminoacizilor
Hormoni si
neurotransmitatori Creatin Poliamine
Carnitin
Uree
CO2
H2O
Nucleotide
Digestia proteinelor
aminopeptidaz
endopeptidaz
H3 N CH CO NH CH CO NH CH CO
R1
R2
R3
HN CH CO
R4
carboxipeptidaz
NH CH CO NH CH COO
R5
NH CH CO
R2
R3
R3 = fenilalanin, tirozin
metionin, leucin
R6
In intestin
Tripsinogen
Enteropeptidaz
Chimotripsinogen
Chimotripsin
Procarboxipeptidaza A
Tripsin
Carboxipeptidaza A
Procarboxipeptidaza B
Carboxipeptidaza B
Absorbia intestinal
Degradarea lizozomalATP-independent
proteaze numite catepsine
n
Calea Ubichitinei
U = protein cu 76 aa
conformaia i
structura primar a proteinei
T1/2
Asp-Arg-Leu-Lys-Phe
O
-
Ubichitin -- C
+ E1-SH
ATP
AMP + PPi
Ubichitin -- C
E2-SH
E1-SH
Ubichitin -- C
3 E3
E2
Proteina condamnat
E2-SH
Ubichitin -- C
E1
NH
Lys
Protein condamnat
Proteazomul
Mediaz degradarea proteinelor ubichitinate,
ATP-dependent
- proteazom 20S (cavitate cilindric cu
activitate proteolitic)
- 19S (complexe proteice la ambele capete)
Capetele au rol n recunoaterea, despturirea
i transportul polipeptidelor n interiorul
cilindrului, printr-un mecanism ATP-dependent.
Catabolismul aminoacizilor
glucoz glicogen
aa diverse lipide.
Dezaminarea aminoacizilor
transaminare
R1 CH COOH + R2 C
NH2
R1 C
COOH
COOH + R2 CH COOH
NH2
COOH
CH2
NADH + H+
NAD+
H2O
CH2
CH2
HC
CH2
COOH
NH2
COOH
Acid glutamic
NH3
CH2
CH2
NH
COOH
COOH
Acid-cetoglutaric
-cetoacid
Aminoacid
Transaminare
Acid-cetoglutaric
Acid glutamic
Dezaminare
oxidativ
NH3
CO2
Ciclul ureogenetic
Uree
Metabolismul amoniacului
Transportul amoniacului
COOH
CH2
NH3 +
Glutaminsintetaz
CH2
HC
NH2
COOH
Acid glutamic
NH2
CH2
CH2
ATP
ADP+Pi
HC
NH2
COOH
Glutamin
NH2
NH2
Glutamin
HOOC
Acid glutamic
NH2
Biosinteza ureei
ciclul ureogenetic sau ciclul Krebs-Hensleit
NH4+
CO2
MITOCONDRIE
-
HCO3 + NH4
2 ATP
2 ADP + 2 Pi
O
H2N C
O C
OPO3H2
NH2
NH
Carbamil fosfat
Pi
(CH2)3
HC
Ornitin
NH2
Citrulin COOH
NH2
(CH2)3
HC
COOH
NH2
Citrulin
COOH
Ornitin
HC
ATP
O
H2N C
AMP + 2 Pi
COOH
Acid argininsuccinic
H2O
H 2N
NH 2
Acid aspartic
NH 2
Uree
CH2
Arginin
C
NH2 +
CH2
HC
NH
COOH
NH
COOH
(CH2)3
HC
COOH
NH2
COOH
C
C
C
NH
(CH2)3
HC
COOH
Fumarat
NH 2+
NH2
COOH
CITOSOL
Carbamil
fosfat
Ornitin
Uree
Acid -cetoglutaric
Acid
aspartic
Citrulin
CICLUL
UREOGENETIC Acid arginin-
acid glutamic
Acid oxaloacetic
succinic
Arginin
Transaminare
Ciclul acizilor
tricarboxilici
Acid
fumaric
Acid aspartic
Transaminare
Piruvat
Decarboxilare
Acid oxaloacetic
Gluconeogenez
+ Acetil~SCoA
Citrat
Glucoz
Hiperamonemia
Acid -cetoglutaric
Glutamat
dehidrogenaz
NH3
Acid glutamic
Glutamin
sintetaz
Glutamin
Consecine ?
Ameliorare prin:
regim alimentar srac n proteine i prin
adaosul n hran a unor a-cetoacizi.
Alanin
Glicin
Cistein
Serin
Treonin
Triptofan
Piruvat
Leucin
Lizin
Fenilalanin
Triptofan
Tirozin
Triptofan
Izoleucin
Leucin
Glucoz
Acetil-CoA
Acetoacetil-CoA
Fosfoenolpiruvat
Corpi cetonici
Asparagin
Aspartat
Aspartat
Tirozin
Fenilalanin
Metionin
Treonin
Valin
Izoleucin
Oxaloacetat
CICLUL KREBS
Citrat
Fumarat
Succinil-CoA
-cetoglutarat
Glutamat
Glutamin
Arginin
Histidin
Prolin
Glucogenici
Cetogenici
GlucogeniciCetogenici
Alanin
Lizin
Izoleucin
Arginin
Leucin
Fenilalanin
Aspartat
Triptofan
Asparagin
Tirozin
Cistein
Glutamat
Glutamin
Glicin
Histidin
Metionin
Prolin
Serin
Treonin
Valin
OH
H2O + Dihidrobiopterin
O2+ Tetrahidrobiopterin
CH2
HC
CH2
HC
NH2
COOH
NH2
COOH
Tirozin
-cetoglutaric
Glu
NAD+
Fenilalanin
CH2
NADH+H
HC
CH2
C
COOH
Acid fenil-piruvic
NAD+
NADH+H+
OH
COOH
Acid fenil-lactic
O
C
H2O
+ Gln
CO2
CH2
-H2O
COOH
Acid fenil-acetic
NH 2
CH2
CH2
CH2
O C NH CH
COOH
Fenilacetilglutamin
NADP+
NADPH + H+
H
N
H2 N
N
H
H 2N
CH CH CH3
OH OH
N
OH
OH OH
H2O
H2C CH COO-
NH3+
L-Fenilalanin
CH CH CH3
Dihidrobiopterina
O2
NH3
Tetrahidrobiopterina
H2C CH COO
HO
L-Tirozin
Acumulare metabolii
oligofrenie fenilpiruvic
(leziuni
Intoleran la:
aspartam (ndulcitor)
COO
+
CH2
H3 N CH CO
CH2
NH CH CO OCH3
L-aspartil-L-fenilalanin-1-metil ester
L-Dopa
Tirozin
Dopamin
(neurotransmittor)
Norepinefrin
(neurotransmittor)
Epinefrin
(hormon)
L-Dopa
Dopachinon
Tiroxin
(hormon)
Melanine
(pigmenti)
OH
OH
O
OH
Oxidare
Transaminare
CH2
HC
CH2
NH2
COOH
CH2
O
COOH
Acid p-hidroxifenil-piruvic
Tirozin
OH
Acid 2,5-dihidroxifenil piruvic
OH
Decarboxilare
oxidativ
Oxidare
CH2 CO CH2 COOH
Homogentizat oxidaz
HOOC
CH
Acidul fumaril acetoacetic
HOOC
CH2 CO COOH
COOH
Chinol
O
HC
OH
Transpozitie
chinolic
OH
Acid homogentizic
Hidroliz
CH CH COOH + H3 C
Acid fumaric
CH2 COOH
CH2 COOH
O Acid aceto-acetic
CH COOH
Transaminare
NH2
(leucin, izoleucin sau valin)
-cetoacid
dehidrogenaza
R
C
O
COOH
CoA-SH + NAD+
SCoA
O
Acil-CoA
CO2+ NADH + H+
N
N
H
L-aminoacid-decarboxilaza
NH2
Histidina
N
N
CO2
Histamina
CH2 CH COOH
NH2
HO
Triptofan
CO2
HO
Degradare
H
Acid 5-hidroxiindolacetic
Serotonina
H3 CO
Melatonin
NH2
H
L-aminoacid-decarboxilaza
HO
CH2 COOH
N
CH2 CH COOH
Triptofanhidroxilaza
Glutamat
decarboxilaza
CO2
Sinteza creatinei i a
fosfocreatinei
CH2
CH2
COOH
CH3
H 2N
H2O
Adenin
H2 C
L-Metionin
OH
OH
ATP
Pi + PPi
C
CH 2
CH 2
+
L-Metioninadenoziltransferaz
CH2
Adenin
O
CH 3
OH
OH
S-Adenozil-L-Metionin
("metionin activ")
H2 N
NH2
NH
Ciclul
ureogenetic
(CH2)3
HC
NH2
COOH
Arginin
H2N CH2 COOH
Arginin-glicin
Glicin
transamidinaza
(Rinichi)
Ornitin
NH2
HN
C
NH
NH CO
CH2 COOH
HN
NH2
HN
Guanidoacetat
metil-transferaz
(Ficat)
S-Adenozilhomocistein
C
CH2
ATP
CH2
CH3
Creatinin
H2O + Pi
Neenzimatic
(Muschi)
Creatin kinaza
(Muschi)
COOH
CH3
Creatin
(Acid N-metil guanidoacetic)
ADP
NH~PO3H2
HN
C
N
CH2 COOH
CH3
Creatin fosfat
Biosinteza glutationului
Glutationul (g-glutamil-cisteinil-glicin) se
sintetizeaz direct din cei trei aminoacizi,
pentru fiecare dintre legturile peptidice
care se formeaz consumndu-se cte o
molecul de ATP
NH2
COOH
Acid glutamic
CO NH CH COOH
CO NH CH CO
CH2
CH2 -glutamil-cistein- CH2
CH2 NH
CH2
+ H2N CH2 COOH
sintetaz
CH2
CH2
SH
SH CH2
SH
Cistein
GlutationHC NH2
HC NH2
COOH
sintetaz
ATP
ATP ADP+Pi
ADP
COOH
COOH
+Pi
Glutation
-glutamil-cistein
Glu
-Glu-Cys
5-Oxoprolin
Cys
Aminoacid
-Glu-Aminoacid
Gly
Cys-Gly
-Glu-Cys-Gly
Citosol
Membran
-GT
Aminoacid
-glutamil-transpeptidaza (-GTcrete n
snge n afeciuni hepatice i hepatobiliare.
-cetoglutarat
3-Fosfoglicerat
Oxaloacetat
Glutamat
Glutamin
Glicoliz
Aspartat
Prolin Arginin
Serin
Lizin
Asparagin
Treonin
Familia glutamatului
Metionin
Cistein Glicin
Familia serinei
Izoleucin
Familia aspartatului
Glicoliz
Fosfoenolpiruvat
Eritrozo 4-fosfat
Fenilalanin
Tirozin
Triptofan
Ribozo 5-fosfat
Histidin
Piruvat
Alanin
Leucin
Valin
Familia piruvatului
COO
COO
Glutamatdehidrogenaz
CH2
COO
CH2
CH2
CH2
CH2
HC
NAD+
(NADP+)
NH2
COO
NADH+H
(NADPH+H+)
NH3
NH
-
NH2
-
Glutamat
CH2
C
COO
Glutaminsintetaz
O
-
-cetoglutarat
CONH2
+ NH3 + ATP
CH2
COO
COO
CH2
HC
H2O
Iminoglutarat
Glutamat
COO
CH2
+ ADP + Pi
CH2
HC
COO
NH2
-
Glutamin
Metabolismul
hemului
N
H
NH
Pirol
IV
7
II
8
7
I
II
IV
III
Porfinogen
III
6
5
Porfin
8
HN
P
A
P
II
III
P
A
P
A
A
IV
CH CH2
H3C
I
H3C
IV
CH2
-
O OC
II
CH CH2
III
CH2
O OC
Fe2+
N
CH2
-
CH3
CH2
CH3
Biosinteza hemului
succinil~CoA.
Etapele biosintezei:
formarea porfobilinogenului;
H2C
NH2
COOH
glicocol
CH2 -aminolevulinat
+
sintaza
CH2
CO-SCoA
succinil-CoA
COOH
CH2
CoA-SH
CH2
C
HC
-aminolevulinat
O
sintaza
NH2
COOH
acid -amino-ceto-adipic
CO2
CH2
CH2
C
H2C NH2
-aminolevulinic
(ALA)
H2N
Formarea porfobilinogenului
(n citosol)
CH2
C
CH2
H2N
COOH
COOH
COOH
COOH CH2
CH2
COOH CH2
CH2 -aminolevulinat
C
dehidrataza
CH2
CH2
CH2
CH2
CH2
CH2
CH
2 H2O
H2N
CH2
CH2
H2N
N
H
porfobilinogen
Formarea protoporfirinei IX
A
H2N
C
CH2
CH
N
H
H2C
Porfobilinogen
dezaminaz
CH 2
N
H
NH
H2C
CH 2
porfobilinogen
P
HN
H
N
4 NH3
uroporfirinogen I
CH
CH2
H2N
Porfobilinogen
dezaminaz
+
Uroporfirinogen III
cosintetaz
N
H
porfobilinogen
H2C
CH 2
N
H
NH
H2C
CH 2
HN
H
N
4 NH3
uroporfirinogen III
P
M
H2 C
CH 2
N
H
NH
Uroporfirinogen
decarboxilaz
HN
H
N
H2C
NH
CH 2
H
N
H2C
4 CO2
HN
H2 C
CH 2
N
H
CH 2
A
P
uroporfirinogen III
coproporfirinogen III
O2
Coproporfirinogen oxidaz
HC
N
H
N
M
N
V
HC
CH
H2C
Protoporfirinogenoxidaz
H
N
2 H2O
CH
2 CO2
Protoporfirin IX
CH 2
N
H
NH
H2C
CH 2
HN
H
N
6H
Protoporfirinogen IX
HC
CH
N
H
N
HC
CH
Protoporfirin IX
CH
+ Fe2+
H
N
HC
M
N
Ferochelataz
N
P
Fe2+
M
N
HC
CH
Hem
Citosol
Uroporfirinogen I
4 NH3
Succinil~SCoA
-ALAS
Glicin
4 Porfobilinogen
H2O
CO2
4 NH3
Aporepresor
Uroporfirinogen III
HEM
Protoporfirin IX
4 CO2
Coproporfirinogen III
Protoporfirinogrn IX
2 CO2
O2
8 Glicin + 8 Succinil~SCoA
-ALAS
8 CoA-SH + 8 CO2
8 Acid -aminolevulinic
ALA
dehidrataz
8 H2O
8 Porfobilinogen
Porfiria acut
intermitent
Uroporfirinogen I
sintaz
4 NH3
Uroporfirinogen I
Porfiria
eritropoetic
congenital
Uroporfirinogen III
sintaz
Uroporfirinogen III
Porfiria
cutanat tardiv
Uroporfirinogen
decarboxilaz
4 CO2
Coproporfirinogen III
Coproporfiria
ereditar
Protoporfiria
Coproporfirinogen
oxidaz
Catabolismul hemului
SRO
NADP+
CH
Biliverdin
reductaz
N
H
CH
CH
Bilirubin
V
CH 2
NADPH
CH
N
H
CH
Biliverdin
M
HC
Fe2+
CO
GC
GTP
Fe3+
Hemoxigenaza
CH
Hem
NADPH
HC
NADP+
CH
N
N
GMPc
NADPH Citocrom
P450 reductaza
Reticul endoplasmic
Fe-ATP-az