Amino catabolism
10 important questions on Amino catabolism
What is the the general reaction of transaminases (=aminotransferase)? Of specific ones?
- amino acid + alfa-ketoglutarate -> glutamate + alfa-keto acid
- aminotransferase
Specific reaction
- Aspartate + alfa-ketoglutarate -> oxaloacetate + glutamate
- -> aspartate aminotransferase
- <- glutamate oxaloacetate transaminase
- Alanine + alfa-ketoglutarate -> pyruvate + glutamate
- -> alanine aminotransferase
- <- glutamate pyruvate transaminase
Transamination reactions are reversible and can be used for the synthesis of amino acid form alfa keto acid
To what is the amino group of glutamate converted to?
- the formed glutamate undergoes oxidative deamination by the enzyme glutamate dehydrogenase. Reaction products are NH4+ and alfa-ketoglutarate
- Glutamate + NAD(P)+ -> alfa-ketoglutarate + NH4+ + NAD(P)H + H+
- NAD+ and NADP+ are electron acceptor
- in mitochondria toghether with some of the other enzymes of the urea cycle
- needs to be efficiently removed -> toxic
What is the sum of reaction catalyzed by aminotransferase and glutamate dehydrogenase
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Into which amino acid can nitrogen also be transported as?
- reaction in the muscle (and other peripheral tissues)
- NH4+ + Glutamate + ATP → Glutamine + ADP + P
- Glutamine synthetase
- Fuel
- Nitrogen donor for purin biosynthesis
- pH regulation (kidney)
What is the urea cycle?
- Synthesis of urea only in liver
- Compartementalisation
- mitochondrial matrix
- cytoplasma
- Nitrogen atoms comes from NH4+ and Aspartate
- Carbon atom derived from hydrogen carbonate (HCOH-, hydration of Co2)
What is the first step of the synthesis of urea in the mitochondria martix? Second step?
- carbamoyl-phosphate (CP) synthetase
- feed forward activation by arginine -> allosteric activtor: N-acetylglutamate which activates more CP synthetase
Creation of Citrulline by Ornithine + carbamoyl phosphate
-> Citrulline exported to the cytoplasma
What do the other reactions in the urea cycle take place?
Cytoplasma
- 4 ATP consumed ti synthesize 1 molecule of urea (3 in the reaction and 1 to make AMP and ATP from the 2 ADPs)
How does the degradation occur of aromatic amino acids?
- converted to acetoacetate, fumarate, pyruvate
- for degradation oxygen O2 required to break opent the aromatic ring
- Monooxygenase (1 oxygen appear in product, 1 in H2O)
- dioxygenases (both oxygen atoms appear in product)
How does the degradation of phenylalanine and tyrosine happen?
- phenylalanine hydroxylase (=monooxygenase)
- electron donor tetrahydrobiopterin
After transamination tyrosine is degraded in for steps to acetoacetate and fumarate
- Dioxygenase
What is phenylketonuria (PKU) disease?
- Deficiency in the enzyme phenylalanine hydroxylase
- phenylalanine accumulates and not converted to tyrosine
- autosomal recessive disorder
- when untreated sever mental retardation
- diagnosis: newborn heel prick
- Treatment: low-phenylalanine diet, supplemented with tyrosine
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