protein turnover catabolism of amino acids ii istván léránt
TRANSCRIPT
Protein turnoverCatabolism of amino acids II
István Léránt
Protein turnover. Catabolism of amino acids 2
CATABOLISM OF AMINO ACIDS ‚C’
PyruvateAcetyl-CoAAcetoacetyl-CoAAlpha-ketoglutarateSuccunyl-CoAFumarateOxalacetate
Protein turnover. Catabolism of amino acids 3
CATABOLISM OF AMINO ACIDS ‚C’
• Ketoplastic amino acids– Acetyl-CoA– Acetoacetyl-CoA
• Glucoplastic amino acids– Pyruvate– Alpha-ketoglutarate– Succinyl-CoA– Fumarate– Oxalacetate
• Gluco- and ketoplastic amino acids
PyruvateAcetyl-CoAAcetoacetyl-CoAAlpha-ketoglutarateSuccunyl-CoAFumarateOxalacetate
Protein turnover. Catabolism of amino acids 4
Formation of amphibolic intermediers
Glucoplastic Ketoplastic Gluco- and ketoplastic
Ala, Arg, Asp, Cys, Glu, Gly, His, Hyp, Met, Pro,
Ser, Thr,Val
Leu Ile, Lys, Phe, Trp, Tyr
Protein turnover. Catabolism of amino acids 5
Protein turnover. Catabolism of amino acids 6
CATABOLISM OF AMINO ACIDS ‚C’
Degradation of AlaSerCysThrresults in pyruvate formation
glutamate piruvate ateketoglutar- alanine ALAT
-232
4edehydratas serine
SCN;SO S;HCystein
NHpyruvate serine
Protein turnover. Catabolism of amino acids 7
Carbon skeleton is degraded to pyruvate
L-Treonine
L-Glycine
L-Serine
Pyruvate
Acetil-KoA
L-Alanine L-Cysteine
Cystine
Pyruvate-dehydrogenase
CO2 + NH4+
Protein turnover. Catabolism of amino acids 8
Protein turnover. Catabolism of amino acids 9
CATABOLISM OF AMINO ACIDS ‚C’Degradation ofAspAsnResults in oxaloacetate
NH3+
COO-
OH
O
-OOC
O
COO- NH3+
COO- -OOC
OCOO-
OH O
+ +
L-aszpartát a-ketoglutarát L-glutamát oxálacetát
NH3+
COO-
NH2
O
NH3+
COO-
OH
O
OH2 NH3+
L-asparagine L-aspartate
+
L-aspartate a-ketoglutarate L-glutamate oxaloacetate
Protein turnover. Catabolism of amino acids 10
Protein turnover. Catabolism of amino acids 11
CATABOLISM OF AMINO ACIDS ‚C’Degradation ofGlnGluProArgHisResults in formation of a-ketoglutarate
12
CATABOLISM OF AMINO ACIDS ‚C’Degradation ofGlnGluProArgHisresults in a-ketoglutarate
His – precurcorHistamine (biogen amine)Carnosine (dipeptide, brain, muscle)
Protein turnover. Catabolism of amino acids
Protein turnover. Catabolism of amino acids 13
CATABOLISM OF AMINO ACIDS ‚C’Degradation ofGlnGluProArgHisresults in a-ketoglutarate
His – precurcorHistamine (biogen amine)Carnosine (dipeptide, brain, muscle) Histidinaemia, histidinuria
Histidase deficiency[histamine] á, [imidazole] á In blood, urine, cerebrospinal fluidDecreased [urocanic acid]
Rare, autosomal recessiveAsymptomatic, later hyperactivity, impeded speach
Protein turnover. Catabolism of amino acids 14
CATABOLISM OF AMINO ACIDS ‚C’Degradation ofGlnGluProArgHisresults in a-ketoglutarate
His – precursor of HistamineHistamine (biogen amine)Carnosine (dipeptide, brain, muscle)
Folic acidLaboratory test in folic acid deficiencyFiglu (Form-imino-glutamate) á
Protein turnover. Catabolism of amino acids 15
CATABOLISM OF AMINO ACIDS ‚C’Degradation ofGlnGluProArgHisresults in a-ketoglutarate
Protein turnover. Catabolism of amino acids 16
CATABOLISM OF AMINO ACIDS ‚C’Degradation ofGlnGluProArgHisresults in a-ketoglutarate
Proline oxydase, pyrroline-5-carboxylate dehydrogenase
Hyperprolinaemia I Hyperprolinaemia I: prolin-dehydrogenase (Hz –symptoms of hyperprolinaemia)
Hyperprolinaemia IIHyperprolinaemia II: Glutamate- -g semialdehyd dehydrogenase (hyperhydroxypolinaemia, Hz absence of symptoms of hyperprolinaemia),
Protein turnover. Catabolism of amino acids 17
Protein turnover. Catabolism of amino acids 18
CATABOLISM OF AMINO ACIDS ‚C’Catabolism results in formation of succinyl-CoA
MetValIle
ß-oxidation of fatty acids of odd-numbered chainCholesterol – bile acids
Biotin Vit B12
Protein turnover. Catabolism of amino acids 19
CATABOLISM OF AMINO ACIDS ‚C’Catabolism results in formation of succinyl-CoA
MetValIle
a-ketobutyrate
Propionyl-CoA
Methylmalonyl-CoA
Succinyl-CoA
Met
Val
Leu
Protein turnover. Catabolism of amino acids 20
CATABOLISM OF AMINO ACIDS ‚C’Catabolism results in formation of succinyl-CoA
MetValIle
Protein turnover. Catabolism of amino acids 21
CATABOLISM OF AMINO ACIDS ‚C’
• Hyperhomocysteinemia / hyperhomocysteinaemia [homocysteine] blood áá
– Pyridoxine / (B6)
– folic acid (B9)
– Vitamin B12
• Deficiency of • methylentetrahydrofolate
reductase methioninsynthetase • Risk factor for recurrent venous
thrombosis
MetValIle
Protein turnover. Catabolism of amino acids 22
CATABOLISM OF AMINO ACIDS ‚C’
a-ketoacid-dehydrogenase
Leu Val Ile
Transaminase activity
a-ketoacid derivative
CO2 + Acyl-CoA tioester
a,ß-unsaturated acyl-CoA thioester
ß-Hydroxymethyl-Glutaryl-CoA
LeuSuccinyl-CoA
Val
Propionyl-CoA+ Acetyl-CoaIle
Protein turnover. Catabolism of amino acids 23
CATABOLISM OF AMINO ACIDS ‚C’
Branched alpha-keto acid dehydrogenase multienzym complex
Alpha-ketoglutarate dehydrogenase
PDH
(Maple Syrup Urine Disease)
Methylmalonic aciduria
Propionic acidemia
PDH