Embed Size (px)
DESCRIPTION
The a -amino group. Tr ansamination Exception Pro Hyp Thr Lys. Catabolism of carbonic skeleton of amino acids. Medical importance: Disease - low frequency Mental retardation Prenatal diagnosis Postnatal diagnosis - treatment. Catabolism of carbon skeleton. Ala, Cys, Gly, Hyp, - PowerPoint PPT Presentation
Citation preview
The -amino group
• Transamination
• Exception– Pro– Hyp– Thr– Lys
Catabolism of carbonic skeleton of amino acids
• Medical importance:– Disease - low frequency– Mental retardation– Prenatal diagnosis– Postnatal diagnosis - treatment
Catabolism of carbon skeleton
Amphybolic intermedier
Glucoplastic
13
ketoplastic
1Gluco- and ketoplastic
5
Ala, Arg, Asp, Cys, Glu, Gly, His, Hyp, Met, Pro, Ser, Thr,
Val
Leu Ile, Lys, Phe, Trp, Tyr
-Ketoglutarate
Succinyl-CoA
Fumarat
l-GlutamateArg, HisGln, Pro
Ile, Met,Val
Tyr, Phe
Citrat cyclus
Oxalacetat
l-Aspartatl-Asn
CitrateAcetyl-CoA
Pyruvate
Ala, Cys,Gly, Hyp,Ser, Thr
Ile, Leu,Trp
Leu,Lys,Phe,Trp,Tyr
Acetoacetyl-CoA
Asn, Asp - Oxaloacetate
• Asparaginase
• Transaminase
H C NH3+
COO-
CH2
CO
NH2
H C NH3+
COO-
CH2
CO
OH
H C
COO-
CH2
CO
OH
O
H2O NH4+ Pyr Ala
Aszparagináz Transzamináz
-Ketoglutarate
Succinyl-CoA
Fumarat
l-GlutamateArg, HisGln, Pro
Ile, Met,Val
Tyr, Phe
Citrat cyclus
Oxalacetat
l-Aspartatl-Asn
CitrateAcetyl-CoA
Pyruvate
Ala, Cys,Gly, Hyp,Ser, Thr
Ile, Leu,Trp
Leu,Lys,Phe,Trp,Tyr
Acetoacetyl-CoA
Gln & glu -ketoglutarate
• Glutaminase
• Transaminase
H C NH3+
COO-
CH2
CH2
NH2
OC
H C
COO-
CH2
CO
OH
O
H2O NH4+ Pyr Ala
Transzamináz
CO
OHCH2
CH2
COO-
NH3+CH
Glutamináz
Proline Arginine
L-glutamat--semialdehyd
L-Glutamat
-ketoglutarate
Pro - -ketoglutarate
Pro - -ketoglutarate (1)
+N
CO-
O
H
HH
H
l-prolin
NAD+
NADH2
CO-
O
NH+
NH3+
CHC
O
O-
CH2
CH2
CH2
C-HO
l-glutamát--szemialdehidH2O
Prolin-dehidrogenáz
Pro - -ketoglutarate (2)
NH3+
CHC
O
O-
CH2
CH2
CH2
C-HO
l-glutamát--szemialdehid
NH3+
CHC
O
CH2
CH2
CH2
-OOC O-
NADH2
NAD+
Glutamát szemialdehid reduktáz
-ketoglutarát
Pro - -ketoglutarate
• 2 autosomal recessive hyperprolinemia– Hyperprolinaemia I: prolin-dehydrogense (Hz –
symptoms of hyperprolinaemia)– Hyperprolinaemia II: Glutamate-semialdehyd
dehydrogenase (hyperhydroxypolinaemia, Hz absence of symptoms of hyperprolinaemia)
Arg & ornitin - -ketoglutarate
l-glutamát--szemialdehid
Ornitin
NH3+
CHC
O
O-
CH2
CH2
CH2
C-HO
l-Glutamát
-ketoglutarát
NH3+
CHC
O
O-
CH2
CH2
CH2
NH3+
NH3+
CHC
O
O-
CH2
CH2
CH2
N
H
C
N+H
H2NArgináz
H2O
UREA Transzamináz
Arg & ornitin - -ketoglutarate
• The defect of ornitin aminotransferase results in:
• [ornitin] is enhanced, blindness.
• Hyperornitinaemia – hyperammonaemia syndrom: [ornitin]plazma is enhanced. Lowered mitochondrial transport.
L-His - -ketoglutarate
L-His
Histidase Histidinaemia
Urokanate
Urokanase Urokaninic acidaemia
4-imidazolon-5-propionate
~ dehidrogenase
F(iglu)
Glutamate forminino transferase Folic acid deficiency / test
L-Glu
transaminase
-ketoglutarate
L-His - -ketoglutarate
L-His - -ketoglutarate
• Histininaemia– Histidase enzyme defect: 1:11500
– [His]blood, urine is elevated
– Typical impediment in speech, benign syndrome
• Urokaninic aciduria
– Autosomal recessive inheritance
– [His]urine is elevated
– benign syndrome
-Ketoglutarate
Succinyl-CoA
Fumarat
l-GlutamateArg, HisGln, Pro
Ile, Met,Val
Tyr, Phe
Citrat cyclus
Oxalacetat
l-Aspartatl-Asn
CitrateAcetyl-CoA
Pyruvate
Ala, Cys,Gly, Hyp,Ser, Thr
Ile, Leu,Trp
Leu,Lys,Phe,Trp,Tyr
Acetoacetyl-CoA
Amino acids - pyruvate
L-Threonin
L-Glycine
L-Serin
Pyruvat
Acetyl-CoA
L-Alanine L-Cystein
Cystine
Piruvat-dehydrogenase
L-Glycin
• Synthesis of glutathion, creatin, purine skeleton, conjugated bile acids, hem
• Glucoplastic aminoacid
• Catabolism of Gly:– Glycin – Serin – Pyruvate – Acetyl-CoA– Glycine cleavage – Glycine synthase complex
L-Glycin
Serin hydroxymethyl transferase
L-Glycin
Glicin
C
O
O-CH2
NH3+
NAD+ CO2 + NH4+ + NADH + H+
PLP
+
H4-Folát N5N10-CH2-H4-Folát
Cleavage of Gly by mitochondrial glycine synthase complex
• Glycinuria: – 0,6 – 1 g glycin/day – Oxalate-typ neprolyth– Defect in tubular reabsorption of kidneys
• Primary hyperoxaluria– Glycin deamination – glyoxilate, oxalate– Ca-oxalate type neprolyths
L-Glycin
Amino acids - pyruvate
L-Threonin
L-Glycine
L-Serin
Piruvate
Acetyl-CoA
L-Alanin L-Cysteine
Cystine
HO
CH2
CC
O
O-
NH3+
H
H2CC
CO-
O
NH3+
CC
O-
O
H3C
NH2+
CC
O-
O
H3C
O
CC
O-
O
H3C
NH3+
Transzamináz
Szerin - dehidratáz
L-alanin
L-szerin
H2O
Glu
-KG
Piruvát
H2O
NH4+
Amino acids - pyruvate
L-Threonin
L-Glycin
L-Serin
Piruvat
Acetyl-CoA
L-Alanin L-Cysteine
Cystine
Cystin – cystein conversion
Cystein – pyruvate conversion:2 ways
• 2 ways– Direct oxydative: cystein sulfinate– Transamination: 3-merkaptopyruvate
• „activ” sulfate formation (3’-phosphoadenosine-5’-phosphosulfate)
• Glutathion syntesis
• Cystein dioxygenase– Fe2+
– NAD(P)H
• Desulfinase / spontan reaction
L-cisztein
HS
CH2
CH
NH3+
C
O
O-
CH2
CH
NH3+
C
O
O-
SO2-
CH2
CHC
O
O-
SO2-
O
CHC
O
O-
O
H3C
O Cisztein dioxigenáz
Transzamináz
Deszulfináz
-KG
L-Glu
Piruvát
L-cisztein-szulfinát
-szulfinil-piruvát
Cystein – pyruvate conversion:(i) direct oxydative way
Taurine
• 3-merkapto-lactate – in human urin
• ~ + cysteinnel disulfid – in urine
• [merkaptolactat – cystein]urine merkaptolactate – in cystein disulfid uria
L-cisztein
HS
CH2
CH
NH3+
C
O
O-
CH2
CHC
O
O-
SH
O
CHC
O
O-
O
H3C
Transzamináz
Piruvát
-ketosav
-aminosav
CHC
O
O-
H3C
H OH
Szulfuriltranszferáz LDH
NADH + H+
NAD+
2 H
H2S
3-merkaptopiruvát
3-merkaptolaktát
Cystein – pyruvate conversion :(ii) transamination
3'-phosphoadenosine-5'-phosphosulfate, (PAPS).
Amino acids - pyruvate
L-Threonin
L-Glycin
L-Serin
Piruvat
Acetyl-CoA
L-Alanin L-Cysteine
Cystine
CO2 + NH4+
Treonin: treonin aldolase two ways
H3C
CHCH
OH
NH3+
C
O
O-
L - treonin
threonin aldolase
Glycine Methylen H4 folate +CO2+NH4+
Acetaldehyde
L-serine
Piruvate
H3CCH
O
Acetaldehid
H3CC
O
O-
H3C
C
O
S KoA
Acetát
Acetil-KoA
Aldehid-dehidrogenáz
Acetát-tiokináz
FAD
FADH2
H2O
CoASH
H2O
ATP
ADP
Piruvát
Glyoxylate is formed from 4-hydroxyprolin képződik
4-hidroxi-prolin
Hidroxiprolin dehidrogenáz
L-1-Pirroline-3-hidroxi-5-karboxilát
Nem enzimatikus
-hydoxi-l-glutamát--szemialdehid
dehidrogenáz
Eritro--hidroxi-l-glutamát
transzamináz
-keto--hidroxiglutarát
aldoláz
Glioxilát + piruvát
4-hydroxyprolin piruvate & glyoxylate
-hidroxi-L-glutamát-szemialdehid
HCCH
CH2
CH
C
O
O-
NH3+
O
OH
H2ONAD+
NADH2
dehidrogenáz
CH
CH2
CH
C
O
O-
NH3+OH
CO-
O
Eritro--hidroxi-L-glutamát
-KA
-AA
transzamináz
N+
C
O
O-
H HH
HOH
4-hidroxy-L-prolin
N+
C
O
O-
HOH
L-1-Pirrolin-3-hidroxi-5 karboxilát
H2O
HCCH
CH2
CH
C
O
O-
NH3+
O
OH
-hidroxi-L-glutamát-szemialdehid
hidroxiprolin-dehidrogenáz
nem enzimatikus lépés
-KA
-AA
transzamináz
O-
CCH
CH2
C
C
O
O
O-
O
OH
-keto- hidroxiglutarát
-OC
O
C
O
HH3C
CC
O-
O
O
Glioxilát Piruvát
4-hydroxyprolin piruvate & glyoxylate
• Hyperhydroxyprolinaemia: – Hydroxyproline dehydrogenase
– [4-hydroxyproline]plasma
– Autosomal resessive trait– Glutamate--semialdehyde dehydrogenase– L-1-Pyrroline-3-hydroxi-5-carboxilate– Lack of hyperprolinaemia
