BIOC/DENT/PHCY 230

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BIOC/DENT/PHCY 230 LECTURE 4
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Nitrogen Metabolism
Many nitrogen containing compounds eg. Amino
acids, nucleotides, porphyrins,
neurotransmitters
There is no dedicated store for nitrogen or
nitrogen compounds in humans
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Nitrogen Balance
An individuals nitrogen balance is dependent on
a combination of 1) Dietary nitrogen intake 2)
Physiological state
Nitrogen balance status can be 1) In balance 2)
Positive 3) Negative
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1) In balance
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2) Positive
Nitrogen intake gt nitrogen excretion
Possible causes Childhood and adolescent
growth Pregnancy Body building
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3) Negative
Nitrogen intake lt nitrogen excretion
Possible causes Illness Starvation Post-surgery
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Amino acids are the major source of dietary N
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Excess or insufficient dietary amino acid intake
leads to the catabolism of amino acids

• Excess amino acids can be used for energy
• Insufficient dietary amino acids lead to the
  catabolism of proteins
• Insufficient dietary energy leads to the
  catabolism of proteins

• For amino acids to be utilised for energy, they
  must have their a-amino groups removed

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Deamination of amino acids
Deamination generates a carbon skeleton a free
amino group
can be used for anabolic or catabolic reactions
generally excreted
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Some amino acids can be directly deaminated
Serine, threonine and glutamate can be directly
deaminated
Glutamate deamination is catalysed by glutamate
dehydrogenase (GDH)
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Glutamine can be deaminated in a two step process
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Glutamine can also be synthesised from glutamate
Glutamine synthesis is an energy requiring
reaction The reaction is catalysed by glutamine
synthetase (GS)
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Transamination
Those amino acids that can not be directly
deaminated have their amino groups transferred to
specific substrates
These substrates are keto acids found in
intermediary metabolism
a - ketoglutarate oxaloaceatate pyruvate
CAC
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Addition of amino groups to these keto acids
generates amino acids
Most amino acids are deaminated by donating
their a-amino acids to one of these keto acids
Thus the deamination of most amino acids leads to
the production of either glu, asp, ala or gln.
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An example transamination
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Pyridoxal phosphate
Derived from vitamin B6 Takes part in all amino
transferase reactions Forms a Schiff base
intermediate with substrates
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Role of transamination in metabolism
Transamination allows for
1) the generation of amino acids in short
supply 2) the provision of carbon skeletons for
energy generation 3) the safe removal of excess
amino groups
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Free ammonia is a by-product of brain metabolism

• Brain requires large amounts of ATP
• This must be generated via oxidative
  phosphorylation
• Therefore the CAC must function efficiently

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Free ammonia is also produced in muscle

• Amino groups can be liberated
• during normal muscle turnover
• during starvation
• during severe muscle activity

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• Pyruvate is usually abundant in active muscle
• Muscle uses pyruvate as an acceptor keto acid

• Thus in muscle most amino groups are shuttled
  to alanine (via glutamate)
• Alanine is then exported to the liver where the
  amino groups can be liberated

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The take home message

• Nitrogen balance status depends on the intake
  and use of N containing compounds
• Excess N from amino acids must be excreted
• A series of aminotransferase and deamination
  reactions shuttle nitrogen to appropriate
  molecules and tissues
• Brain and muscle can generate large amounts of
  excess nitrogen as part of their metabolism
• The liver is an important tissue for processing
  excess nitrogen