Protein Breakdown and Urea Formation Flashcards
Draw out the different nitrogen balance diagrams
Check diagrams
What are the two parts of metabolism of amino acids?
Unlike carbohydrates and fats, amino acids are either used or broken down but not stored Two parts: Carbon skeleton Nitrogen Carbon skeleton is used for: Energy metabolism Biosynthesis pathways Nitrogen is used for: Nitrogenous compounds Urea
What is transamination?
Transamination is the process by which amino groups are removed from amino acids and transferred to acceptor keto-acids to generate the amino acid version of the keto-acid and the keto-acid version of the original amino acid
a-ketoglutarate, pyruvate and oxaloacetate are a-keto acids
The process of an amino acid to an alpha keto-acid is catalysed by an alpha-amino group
The process of an alpha-keto acid turning into an amino acid is catalysed by a transaminase or aminotransaminase
What transaminases are used?
Two most important are alanine (ALT) and aspartate (AST) transaminase
In the liver OAA and a-ketoglutarate can be used to make glucose
In the muscle pyruvate can be used in the TCA cycle and ETC to make ATP
High levels of AST and ALT in the blood are indicative of tissue damage, particularly liver and cardiac muscle
How is ammonia formed?
Check diagram**
Its a process called oxidative deamination
Image result for HOw is ammonia formed from oxidative deamination
During oxidative deamination, an amino acid is converted into the corresponding keto acid by the removal of the amine functional group as ammonia and the amine functional group is replaced by the ketone group. The ammonia eventually goes into the urea cycle.
How is free ammonia eliminated?
Ammonia is toxic so has to be removed safely
Levels of ammonia in the blood are low
Free ammonia generated in non-hepatic tissue combines with glutamate to give glutamine
glutamate + NH4+ + ATP—>glutamine + ADP
This is catalysed by glutamine synthase
Glutamine is soluble and readily transported in the blood
How is nitrogen removed?
Ammonia is toxic so has to be removed safely
Levels of ammonia in the blood are low
Nitrogen is transported mainly by the amino acids alanine and glutamine
In mammals the ammonia is converted to the non-toxic neutral compound urea and excreted in the urine
Amino acid nitrogen is transferred to urea in three steps
Transamination, formation of ammonia and synthesis of urea
What is the urea cycle?
The means of excreting nitrogen
Enzymes are present in the mitochondria and are the cytoplasm
Substrates are bicarbonate, aspartate and ammonium ions (released from glutamine or glutamate)
How is urea formed?
NH2 Glutamine
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O=C Carbon skeleton
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NH2 AspartateRecall the urea cycle
Short version:
Citrulline formed in the mitochondria is exported in exchange for ornithine synthesised in the cytosol
Glutamate dehydrogenase and aspartate aminotransferase are found in the mitochondria of the liver
Long version:
Ammonia is formed by the break-down of amino acids/gut bacteria.
The mitochondrial stage:
Carbamoyl phosphate is formed from ammonia and bicarbonate, by CPS.
OTC condenses carbamoyl phosphate and ornithine to form citrulline.
Citrulline is then transported to the cytosol (by SLC25A15).
The cytosolic stage:
AS condenses citrulline and aspartate to form argininosuccinate.
Argininosuccinate is broken down into arginine and fumarate by AL.
Arginine is broken down into urea and ornithine by arginase.
Ornithine translocase transports ornithine into the mitochondria.
What happens in the muscle regarding the urea cycle?
Enzymes of the urea cycle not present
In prolonged exercise or starvation branched amino acids are used for energy (leucine, isoleucine and valine)
Two routes are used to transport nitrogen to the liver- alanine and glutamine
What happens during the glucose-alanine cycle/Cahill cycle?
When in extrahepatic tissues amino acids are used for energy, pyruvate, derived from glycolysis, is used as amino group acceptor, forming alanine, a nonessential amino acid.
Alanine diffuses into the bloodstream and reaches the liver.
In the liver, the amino group of alanine is transferred to α-ketoglutarate to form pyruvate and glutamate, respectively.
The amino group of glutamate mostly enters the urea cycle, and in part acts as a nitrogen donor in many biosynthetic pathways.
Pyruvate enters gluconeogenesis and is used for glucose synthesis.
The newly formed glucose diffuses into the bloodstream and reaches the peripheral tissues where, due to glycolysis, is converted into pyruvate that can accept amino groups from the free amino acids, thus closing the cycle.
Check the fate of the carbon skeleton diagram
Have you checked it????????
