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Metabolism of protein

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Fearoz Khan
Fearoz Khan

The document discusses amino acid catabolism and the urea cycle. It explains that amino acids are first transaminated, removing their amino groups as ammonia. Ammonia is highly toxic, so it is converted to urea via the urea cycle in the liver and excreted in urine. The urea cycle involves several enzymatic steps that incorporate ammonia and aspartate to form the relatively non-toxic urea molecule for excretion. Deficiencies in urea cycle enzymes can cause hyperammonemia, which is particularly dangerous for the brain.

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Metabolism of protein
Dr. Fearoz khan Senior lecturer Biochemistry Rehman Medical College Peshawar 1.Trans amination, Deamination, Urea cycle 2. Specialized products formed from Amino Acids
Formation of Ammonia The first step in the catabolism of amino acids is to remove the amino group as ammonia. Ammonia is highly toxic especially to the nervous system. Detoxification of ammonia is by conversion to urea and excretion through urine. 15
A. Transamination Transamination is the exchange of amino group between amino acid and another keto acid, forming a new alpha amino acid. The enzyme catalyzing the reaction as a group known as transaminases (amino transferases). These enzymes have pyridoxal phosphate as prosthetic group. The reaction is readily reversible. 16
Biological significance of transamination 1. First step of catabolism: Ammonia is removed, and rest of the amino acid is entering into catabolic pathway. 2. Synthesis of non-essential amino acids: By means of transamination, all non-essential amino acids could be synthesized by the body from keto acids available for other sources 18
Clinical significance of transamination Aspartate aminotransferase (AST) is increased in myocardial infarction and alanine amino transferase (ALT) in liver diseases 19
B. Trans-deamination It means transamination followed by oxidative deamination. All amino acids are first transaminated to glutamate, which is then finally deaminated. Glutamate dehydrogenase reaction is the final reaction which removes the amino group of all amino acids. Thus, the two components of the reaction are physically far away, but physiologically they are coupled. Hence, the term trans-deamination 20
Metabolism of protein
Metabolism of protein
Metabolism of protein
Metabolism of protein
Metabolism of protein
Metabolism of protein
Disposal/Detoxification of Ammonia 1. First line of defense (Trapping of ammonia): Even very minute quantity of ammonia may produce toxicity in central nervous system. The intracellular ammonia is immediately trapped by glutamic acid to form glutamine, especially in brain cells. The glutamine is then transported to liver, where the reaction is reversed by the enzyme glutaminase. The ammonia thus generated is immediately detoxified into urea. 22
2. Final disposal: The ammonia from all over the body thus reaches liver. It is then detoxified to urea by liver cells. Then excreted through kidneys. Urea is the end product of protein metabolism 23
Urea Cycle The cycle is known as Krebs-Henseleit urea cycle. As ornithine is the first member of the reaction sequences, it is called as Ornithine cycle. The two nitrogen atoms of urea are derived from two different sources, one from ammonia and the other directly from aspartic acid. 24
Urea molecule 25
Steps of Urea Cycle 1. Formation of Carbamoyl Phosphate. 2. Formation of Citrulline. 3. Formation of Argininosuccinate. 4. Formation of Arginine. 5. Formation of Urea. 26
1 2 ATP + HCO3 - + NH3 Steps of Urea Cycle Carbamoyl phosphate + 2 ADP + Pi Pi Mitochondrion Ornithine. 2 Citrulline Citrulline Ornithine ATP Aspartate3 AMP + PPi5Urea H2O Arginino- succinateArginine 4 Fumarate OxaloacetateMalate 27 Cytosol Urea cycle
28
Regulation of the urea cycle During starvation, the activity of urea cycle enzymes is elevated to meet the increased rate of protein catabolism. The major regulatory steps is catalyzed by CPS-I (Carbamoyl phosphate synthetase-I) where the positive effectror is N-acetyl glutamate (NAG). 29
Disorderers of urea cycle Deficiency of any of the urea cycle enzymes would result in hyperammonemia. If block occur in one of the earlier steps, the condition is more severe, since ammonia itself accumulates. If deficiency occur in later enzymes, this result in accumulation of other intermediates which are less toxic and hence symptoms are less. 30
The accumulation of ammonia in blood (normally less than 50 mg/dl) and body fluids results in toxic symptoms. Brain is very sensitive to ammonia. Child may be put on a low protein diet and frequent small feeds are given. Since Citrulline is present in significant quantities in milk, breast milk is to be avoided in Citrullinemia. 31
Urea level in blood and urine In clinical practice, blood urea level is taken as an indicator of renal function. The normal urea level in plasma is from 20 to 40 mg/dl. Blood urea level is increased where renal function is inadequate. Urinary excretion of urea is 15 to 30 g/day (6-15 g nitrogen/day). Urea constitutes 80% of urinary organic solids. 32

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Metabolism of protein

  • 2. Dr. Fearoz khan Senior lecturer Biochemistry Rehman Medical College Peshawar 1.Trans amination, Deamination, Urea cycle 2. Specialized products formed from Amino Acids
  • 3. Formation of Ammonia The first step in the catabolism of amino acids is to remove the amino group as ammonia. Ammonia is highly toxic especially to the nervous system. Detoxification of ammonia is by conversion to urea and excretion through urine. 15
  • 4. A. Transamination Transamination is the exchange of amino group between amino acid and another keto acid, forming a new alpha amino acid. The enzyme catalyzing the reaction as a group known as transaminases (amino transferases). These enzymes have pyridoxal phosphate as prosthetic group. The reaction is readily reversible. 16
  • 5. Biological significance of transamination 1. First step of catabolism: Ammonia is removed, and rest of the amino acid is entering into catabolic pathway. 2. Synthesis of non-essential amino acids: By means of transamination, all non-essential amino acids could be synthesized by the body from keto acids available for other sources 18
  • 6. Clinical significance of transamination Aspartate aminotransferase (AST) is increased in myocardial infarction and alanine amino transferase (ALT) in liver diseases 19
  • 7. B. Trans-deamination It means transamination followed by oxidative deamination. All amino acids are first transaminated to glutamate, which is then finally deaminated. Glutamate dehydrogenase reaction is the final reaction which removes the amino group of all amino acids. Thus, the two components of the reaction are physically far away, but physiologically they are coupled. Hence, the term trans-deamination 20
  • 14. Disposal/Detoxification of Ammonia 1. First line of defense (Trapping of ammonia): Even very minute quantity of ammonia may produce toxicity in central nervous system. The intracellular ammonia is immediately trapped by glutamic acid to form glutamine, especially in brain cells. The glutamine is then transported to liver, where the reaction is reversed by the enzyme glutaminase. The ammonia thus generated is immediately detoxified into urea. 22
  • 15. 2. Final disposal: The ammonia from all over the body thus reaches liver. It is then detoxified to urea by liver cells. Then excreted through kidneys. Urea is the end product of protein metabolism 23
  • 16. Urea Cycle The cycle is known as Krebs-Henseleit urea cycle. As ornithine is the first member of the reaction sequences, it is called as Ornithine cycle. The two nitrogen atoms of urea are derived from two different sources, one from ammonia and the other directly from aspartic acid. 24
  • 18. Steps of Urea Cycle 1. Formation of Carbamoyl Phosphate. 2. Formation of Citrulline. 3. Formation of Argininosuccinate. 4. Formation of Arginine. 5. Formation of Urea. 26
  • 19. 1 2 ATP + HCO3 - + NH3 Steps of Urea Cycle Carbamoyl phosphate + 2 ADP + Pi Pi Mitochondrion Ornithine. 2 Citrulline Citrulline Ornithine ATP Aspartate3 AMP + PPi5Urea H2O Arginino- succinateArginine 4 Fumarate OxaloacetateMalate 27 Cytosol Urea cycle
  • 20. 28
  • 21. Regulation of the urea cycle During starvation, the activity of urea cycle enzymes is elevated to meet the increased rate of protein catabolism. The major regulatory steps is catalyzed by CPS-I (Carbamoyl phosphate synthetase-I) where the positive effectror is N-acetyl glutamate (NAG). 29
  • 22. Disorderers of urea cycle Deficiency of any of the urea cycle enzymes would result in hyperammonemia. If block occur in one of the earlier steps, the condition is more severe, since ammonia itself accumulates. If deficiency occur in later enzymes, this result in accumulation of other intermediates which are less toxic and hence symptoms are less. 30
  • 23. The accumulation of ammonia in blood (normally less than 50 mg/dl) and body fluids results in toxic symptoms. Brain is very sensitive to ammonia. Child may be put on a low protein diet and frequent small feeds are given. Since Citrulline is present in significant quantities in milk, breast milk is to be avoided in Citrullinemia. 31
  • 24. Urea level in blood and urine In clinical practice, blood urea level is taken as an indicator of renal function. The normal urea level in plasma is from 20 to 40 mg/dl. Blood urea level is increased where renal function is inadequate. Urinary excretion of urea is 15 to 30 g/day (6-15 g nitrogen/day). Urea constitutes 80% of urinary organic solids. 32