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Amino Acid Metabolism


It is divided into 4 stages:

  1. Transamination
  2. oxidative deamination of glutamate
  3. Ammonia transport
  4. Reactions of Urea cycle.
  1. Transamination involves the transfer of an amino group from an amino acid to an a-keto acid to form a new amino acid and new a-keto acid.
    Enzymes: Aminotransferases (Transaminase) for e.g.

Extra Edge:
  1. Pyridoxal phosphate is an essential cofactor for all aminotransferases.
  2. All amino acid undergo transamination reaction except lysine, threonine, proline, hydroxyproline.
  3. Oxidative Deamination of Glutamate
  4. Oxidative Deamination by glutamate dehydrogenase occurs in mitochondrial matrix by the following reaction
  1. Oxidative deamination by amino acid oxidases. They also remove ammonia from a-aminoacid

Amino acid + H2O + O2 ? a-keto acid + NH3 + H2O2

  1. These enzymes use tightly bound flavins as cofactor.
  2. Amino acid oxidases occur in kidney and liver, however their physiologic significance is not clear.
  1. Glutamine synthetase fixes ammonia as glutamine

    1. In addition to fixation of ammonia via glutamate dehydrogenase reaction, formation of glutamine is catalyzed by glutamine synthetase a mitochondrial enzymes present in high quantity in renal tissue.
    2. Synthesis of glutamine is accomplished at expense of hydrolysis of one equivalent of ATP. For e.g.; in brain tissue, the major mechanism for detoxification of NH3 is glutamine formation.
  2. The urea cycle (krebs and henseleit cycle) 

    1. Urea is major end product of protein catabolism in humans.
    2. Synthesis of urea occurs in liver. It is party mitochondrial and partly cytosolic.
    3. Synthesis of 1 mole of urea requires 3 moles of ATP, 1 mole of each of ammonium ion and a- nitrogen of aspartate.
    4. N-acetyl glutamate functions solely as enzyme activator.
  3. Reaction of the Urea Cycle
    The first two reactions occur in the mitochondria, whereas remaining three reactions in the cytoplasm.
    1. Carbamoyl phosphate synthetase 1 catalyzes the formation of carbamoyl phosphate formed from ammonia and carbon dioxide.
      a. Energy requirement. Two molecules of ATP are required for this reaction.
      b. N-Acetylglutamate is a required positive allosteric effector.
    2. Ornithine transcarbamoylase catalyzes the formulation of citrulline from carbamoyl phosphate and ornithine.
    3. Argininosuccinate synthetase catalyzes the formation of argininosuccinate from citrulline and aspartate. One molecule of ATP is required. The amino group of aspartate provides one of the two nitrogen atoms that appear in urea.
    4. Argininosuccinate lyase catalyzes the formation of arginine and fumarate from the cleavage of argininosuccinate. As it is a citric acid cycle intermediate, fumarate formation links the urea cycle and the citric acid cycle.
    5. Arginase catalyzes the formation of urea and ornithine from the cleavage of arginine.
      a.  Urea is highly soluble and nontoxic. It enters the blood and is excreted in the urine.
      b.  Ornithine continues to act as an intermediate in the urea cycle.
  1. Compartmentation of the Urea Cycle enzymes
  1. The mitochondria contain carbamoyl phosphate synthetase and ornithine transcarbamoylase.
  2. The cytosol contains argininosuccinate synthetase, argininosuccinate lyase, and arginase.

Biosynthesis of Urea

  1. Diseases
  1. Type I hyperammonemia is due to a defect in carbamoyl phosphate synthetase.
  2. Type II hyperammonemia is due to a defect in ornithine transcarbamoylase.
  3. Citrullinuria is due to a defect in argininosuccinate synthetase.
  4. Argininosuccinic academia is due to a defect in argininosuccinate lyase.
  5. Hyperargininemia is due to a defect in arginase.
  1. Treatment
  1. Low-protein diets.
  2. Administration of sodium benzoate and sodium phenylacetate
  3. Blood transfusion and hemodialysis                  
  1. Degradation of branched-chain amino acids. 
    Valine, leucine and isoleucine all are converted to their corresponding a-keto acid by the action of a specific aminotransferase, known as branched chain amino acid transaminase (BCAAT).
  2. Branched-chain keto acid dehydrogenase is a common enzyme that catalyzes the oxidative decarboxylations and genetic defect in this enzyme leads To Maple Syrup Urine Disease.  MSUD is detected by burnt sugar smell   



Fig. The catabolism of branched-chain amino acids.


Metabolic Disorders of Branched-Chain Amino Acid Catabolism

  1. The odor of urine in maple syrup urine disease (branched-chain ketonuria) suggests maple syrup or burnt sugar.
  2. The biochemical defect involves the -keto acid decarboxylase complex Plasma and urinary levels of leucine, isoleucine, valine, -keto acids, and -hydroxy acids (reduced -keto acids) are elevated..
  3. Early diagnosis, especially prior to 1 week of age, employs enzymatic analysis.
  4. Prompt replacement of dietary protein by an amino acid mixture that lacks leucine, isoleucine, and valine averts brain damage and early mortality.
  1. Catabolism of phenylanine and tyrosine
  1. Phenylalanine hydroxylase catalyzes the hydroxylation of phenylalanine to form tyrosine and requires tetrahydrobiopterin as cofactor.


  1. Phenylketonuria
  1. Classic Phenylketonuria is due to genetic defect in phenylalanine hydroxylase
  2. A typical phenylketonuria due to defect in dihydrobiopteridine reductase.        
  1. Disorders associated with defects in amino acid transport.
  1. Cystinuria: There is impaired tubular reabsorption and excessive urinary excretion of dibasic aminoacids, lysine, arginine, ornithine & cystine (COLA).
  2. Hartnup’s disease is due to defect in transport system for large neutral and aromatic amino acids.
    The clinical manifestation results from deficiency of essential amino acid tryptophan caused by combination of intestinal malabsorption and renal loss. 
  1. Tyrosine derived biological important compound
  1. Formation of dopa. Tyrosine is hydroxylated to 3, 4-dihydroxyphenylalanine (dopa) by tyrosine hydroxylase, which requires tetrahydrobiopterin (BH4) as a cofactor. This is the rate-limiting step in catecholamine biosynthesis. The enzyme is allosteric, with dopamine, norepinephrine, and epinephrine acting as negative effectors.
  2. Formation of dopamine is catalyzed by dopa decarboxylase,  a PLP –dependent enzyme.
  3. Formation of norepinephrine. Dopamine a–hydroxylase hydroxylates the aromatic ring of dopamine to yield norepinephrine. This enzyme requires copper and vitamin C as cofactor.
  4. Formation of epinephrine from norepinephrine is by phenylethanolamine-N-methyltransferase, using SAM as the methyl donor.

figure. The biosynthesis of biologically important compounds from tyrosine.

Biosynthesis of other amino acid-derived Compounds of Biological Importance


Precursor Amino Acid

Primary Function


Creatine phosphate







Nitric oxide





Glycine, arginine











Fatty acid transporter

Energy storage compound







Vasodilator, neurotransmitter




GABA = γ aminobutyric acid.


NO is formed in the body by L-Arginine (AIIMS May 09)  


Fig: Conversion of methionine to propionyl-CoA.
Protein Structure
Feature Primary Secondary Tertiary Quaternary
Main Bond Peptide H-Bond Hydrophobic Hydrogen & ionic
Functional Activity Absent Present
Denaturation (AIIMS May 08) Retain Lost
Detection of
a. Mass spectrometry
b. Edman’s technique
c. FDNB or Sanger’s method
a. X-ray diffraction crystallography
b. Nuclear Magnetic Resonance(NMR)
Any separation technique
like electrophoresis &


Extra Edge
  1. The Edman method has been largely replaced by mass spectrometry, a sensitive and versatile tool for determining primary structure, for identifying posttranslational modifications, and for detecting metabolic abnormalities.
  2. DNA cloning and molecular biology coupled with protein chemistry provide a hybrid approach that greatly increases the speed and efficiency for determination of primary structures of proteins
  3. Genomics- the analysis of the entire oligonucleotide sequence of an organism’s complete genetic material has provided further enhancements.
  4. Computer algorithms facilitate identification of the open reading frames that encode a given protein by using partial sequences and peptide mass profiling to search sequence databases
  5. The gene-encoded primary structure of a polypeptide is the sequence of its amino acids. Its secondary structure results from folding of polypeptides into hydrogen –bonded motifs such as the ? helix, the ß- pleated sheet, ß bends and loops. Combinations of these motifs can form super secondary motifs.
  6. Tertiary structure concerns the relationships between secondary structural domains. Quaternary structure of proteins with two or more polypeptides (oligomeric proteins) concerns the spatial relationships between various types of polypeptides
  7. Primary structure are stabilized by covalent peptide bonds. Higher orders of structure are stabilized by weak forces -multiple hydrogen bonds, salt (electrostatic) bonds, and association of R groups.

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