Protein turnover.Catabolism of amino acids III

István Léránt

CATABOLISM OF AMINO ACIDS‚C’PheTyrTrp

Role of molecular oxygen

CATABOLISM OF AMINO ACIDS‚C’PheTyrTrp

Role of molecular oxygen

OHNADPTyrH NADPH O Phe 22

CATABOLISM OF AMINO ACIDS‚C’PheTypTrp

CH2 CH COOH

NH2

-ketoglutarát

Glu

CH2 CH COOH

O

Phe

Fenilpiruvát

NADH2NAD+

CH2 CH COO-

OH

Fenillaktát

CH2 COO-

H2O

CO2

NAD+

NADH2

Fenilacetát

CH2 C

O

N C

CONH2

CH2

CH2

COO-

H

FenilglutaminGln

H2O

Phenylketonuria

CATABOLISM OF AMINO ACIDS‚C’

• Phenylketonury– Hyperphenylalaninaemia I:

phenylalanin-hydroxylase– Dihydrobiopterin-reductase

(hyperphenylalanaemia II, III)– Dihydrobiopterin biosynthesis

(hiperphenylalaninaemia IV, V)

PheTyrTrp

CATABOLISM OF AMINO ACIDS‚C’

Plasma (mg/dL) Plasma (mg/dL) Urine (mg/dL) Urine (mg/dL)

Metabolite Normal Phenylketonuric Normal Phenylketonuric

Phenylalanine 1—2 15—63 30 300—1000

Phenylpyruvate 03—1.8 300—2000

Phenyllactate 290—550

Phenylacetate Increased

Phenylacetylglutamine 200-300

PheTyrTrp

CATABOLISM OF AMINO ACIDS‚C’PheTyrTrp

Transzaminázaktivitás

p-hidroxifenil piruvát hidroxiláz

Homogentizinsav oxidáz

Tyrosine-transaminase: Type II tyrosinemia

Neonatal tyrosinemia: p-OH-phenyl-pyruvate hydroxylase

Alkaptonuria: homogentisate oxydase

Fumarylacetoacetate hydroxylase: Type I tyrosinemia

CATABOLISM OF AMINO ACIDS‚C’

• Tyrosinaemia Type I: • Genetical defect of: – fumaryloacetoacetate and

maleylo acetoacetate hydrolase

– [Tyr]plasma 6-12 mg/dl, [Met] á

• Acut tyrosinosis: „cabbage odor”, diarrhea, vomit, death (at age 6-8 months)

• Chronic tyrosinaemy: milder symptoms, death

• (at age 10 years)

PheTyrTrp

CATABOLISM OF AMINO ACIDS‚C’

• Tyrosinaemia type II: • Genetical defect of:

tyrosine transaminase• [Tyr]plasma 4-5 mg/dl• Eye and skin lesions• Mental retardation• Neonatal tyrosinaemia:• Relative lack of p-hydroxy-

phenylpyruvate-hydroxylase• Protein poor diet

PheTyrTrp

CATABOLISM OF AMINO ACIDS‚C’

• Alcaptonuria• Homogentisinic oxydase• 1859 – Theory of Garrod

elmélet• Dark urine may occur• Oochronosis

PheTyrTrp

CATABOLISM OF AMINO ACIDS‚C’PheTyrTrp

Catabolism of tryptophaneTrp à Nicotinamide

Tryptophane oxygenase (inducible) Kinurenine formilaseKinurenine hydroxylaseKinureninase (PLP)

KINURENIN à Niacin (Vitamin B3)

N

C

O

OHNIACIN (B3)

CATABOLISM OF AMINO ACIDS‚C’

• Vitamin B6 deficiency:– Kinurenine is converted into

xanturenate – urine– Synthesis of NAD+ & NADP+ â – Synthesis of pyrimidine â

• Niacin deficiency:– pellagra

• Hartnup-disease:– A family of London (19th

century)– Trp (neutral) amino acid

• Disorder of intestinal and renal transport

PheTyrTrp