protein turnover catabolism of amino acids ii

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 -ketoglutarát L-glutamát oxálacetát

NH3+

COO-

NH2

O

NH3+

COO-

OHO

OH2 NH3+

L-asparagine L-aspartate

+

L-aspartate -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 -ketoglutarate

12

CATABOLISM OF AMINO ACIDS ‚C’Degradation ofGlnGluProArgHisresults in -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 -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 -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 -ketoglutarate

Protein turnover. Catabolism of amino acids 16

CATABOLISM OF AMINO ACIDS ‚C’Degradation ofGlnGluProArgHisresults in -ketoglutarate

Proline oxydase, pyrroline-5-carboxylate dehydrogenase

Hyperprolinaemia I Hyperprolinaemia I: prolin-dehydrogenase (Hz –symptoms of hyperprolinaemia)

Hyperprolinaemia IIHyperprolinaemia II: Glutamate-gsemialdehyd 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

-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’

-ketoacid-dehydrogenase

Leu Val Ile

Transaminase activity

-ketoacid derivative

CO2 + Acyl-CoA tioester

,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