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Amino acid metabolism - Coggle Diagram

- - - - Synthesis of non-essential amino acids
      - Tissue protein synthesis
      - Dietary protein
    - - Catabolism
        
        Ammonia - urea cycle
        
        Carbon skeleton
      - Nitrogen containing compound synthesis
      - Protein turnover
    - - Utilisation and input of sources is equal
      - Disruption
        
        Disease
      - Maintained
        
        Healthy
  - - - Cannot be synthesised by body
    - - Synthesised by body
    - - Catabolism yield pyruvate or intermediate of TCA
        
        Substrates for gluconeogenesis
    - - Catabolism yields acetoacetate, acetyle CoA or acetoacetyl CoA
        
        Not substrates for gluconeogenesis
        
        Can feed into fatty acid synthesis
      - Leucine + lysine
        
        Essential
- - - - Alanine aminotransferase (ALT)
      - Requires vitamin B6
    - - Producing glutamate
  - - - Aspartate aminotransferase (AST)
      - Required vitamin B6
  - - - Producing ammonia
    - - Glutamine is nitrogen donor (not free NH\(_3\))
    - - Reduced asparagine to tumour cells
        
        Inhibits cell proliferation
  - - - Can be formed or degraded by aminotransferases or glutamate dehydrogenase
    - - Cofactors
        
        Aminotransferases need PLP
        
        Glutamate dehydrogenase needs either NAD\(^+\) or NADPH
      - Oxidative deamination by glutamate dehydrogenase
        
        Readily reversible
        
        Determination of NAD\(^+\) or NADP\(^+\) depends on direction of reaction
        
        One of 3 enzymes capable of incorporating free ammonia into an organic compound
    - - Non-toxic, transport form of ammonia from peripheral tissues (important in brain)
      - In peripheral tissues glutamate converted to glutamine
        
        Glutamine synthetase
        
        Requires ATP + free ammonia
      - Renal tissue glutamine converted to glutamate
        
        Glutaminase
        
        Ammonia released
        
        Acid-base homeostasis in renal tubule
    - - Via combined actions of glutamate dehydrogenase + glutaminase
  - - - Homocysteine has 2 possible fates
        
        Conversion back to methionine
        
        By methionine synthase
        
        Vit B12 coenzyme
        
        THF (oxolane) substrate
        
        Transfer of sulphur group to serine
        
        By cystathionine-\(\beta\) synthase
        
        PLP cofactor
        
        Production of cystathionone
        
        Converted to cysteine + \(\alpha\)-ketobutyrate
        
        By cysthionase
        
        PLP cofactor
        
        \(\alpha\)-ketobutyrate converted to succinyl-CoA
        
        Production of cysteine
        
        Converted to sulphate
        
        Pathway produces glutamate + pyruvate
        
        Combined with ATP to form PAPS
        
        Excreted in urine
- - - - BCAA present in most protein sources
      - 3 BCAA are essential
      - Catabolic states metabolise tissue protein
        
        Amino acids released to metabolism
- - - - Removal and conversion of amino group to ammonia or aspartate
  - - - Glutamate feeds excess NH\(_4^+\) into urea cycle
    - - Specific to each amino acid
    - - From vitamin B6
      - Pyridoxine from pyridoxal-5'-phosphate (PLP)
        
        Carries amino group
        
        PLP covalently attached to enzyme via Schiff base formation through condensation of PLP's aldehyde group with amino group
    - - Catalysed by
        
        Glutamate dehydrogenase
        
        Glutamine synthetase
  - - - D-amino acids interfere with metabolism of L-amino acids
    - - D-amino acids present in body
        
        Passed from blood stream to colon
    - - Enzyme D-amino acid oxidase (D-AAO)
- - - - Including standard reactions of fatty acyl-CoA oxidations + ketone body formation
- - - - Dehydrogenation
        
        Formation of C=C
      - PDH complex
      - Generation of acyl-CoA derivatives
    - - Glutamate
- - - - Classical PKU
        
        Complete/severe enzyme reduction
      - PKU-I
        
        Enzyme maintains some function
    - - Metabolised to
        
        Phenylpyruvate
        
        Phenylacetate
        
        Phenyllactate
      - Products excreted in urine
        
        Mousey/musty smell
    - - Becomes essential amino acid
    - - Conversion of tyrosine to melanin inhibited by phenylalanine
    - - If untreated
        
        Permanent intellectual disability
        
        Seizures
        
        Delayed development
        
        Behavioural problems
        
        Psychiatric disorders
    - - Heel-prick test
    - - Amino acid restriction
        
        Low-protein diet
      - Avoid asparatame
        
        Converts to phenylalanine
      - Tyrosine supplements
      - Regular monitoring of blood phenylalanine
    - - Low birth weight
      - Delayed development
      - Facial abnrmalities
      - Abnormally small head
      - Heart defects
      - Intellectual disability
      - Behavioural problems
  - - - Mild
        
        Temporary low muscle tone
      - Severe
        
        intellectual disability,
        
        movement disorders,
        
        difficulty swallowing,
        
        seizures,
        
        behavioural problems,
        
        progressive problems with development,
        
        inability to control body temperature
    - - BH\(_4\) supplementation
        
        2-20mg/kg per day
- - - - Phenylalanine converted to tyrosine
        
        By phenylalanine hydroxylase
        
        Tetrahydrobiopterin (BH\(_4\)) required
        
        Utilisation + regernation of BH\(_4\)
        
        Series of cyclic reactions
        
        Regenerated after use in phenylalanine hydroxylase reaction
        
        Also formed in priming reaction
        
        By dihydrofolate reductase
      - Tyrosine transaminated by tyrosine aminotransferase
        
        Glutamate + \(p\)-Hydroxyphenylpyruvate produced
        
        Decarboxylation by hydroxyphenylpyruvate decarboxylase
        
        Produces homogentisate
        
        Oxidation then hydrolysis
        
        Fumarate + acetoacetate produced
        
        By homogentisate oxidase + fumarylacetoacetate hydrolase