BIOC/DENT/PHCY 230 LECTURE 4. Nitrogen Metabolism Many nitrogen containing compounds eg. Amino acids, nucleotides, porphyrins, neurotransmitters There.
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BIOC/DENT/PHCY 230
LECTURE 4
Nitrogen Metabolism
Many nitrogen containing compounds
eg. Amino acids, nucleotides, porphyrins, neurotransmitters
There is no dedicated store for nitrogen or nitrogen compounds in humans
Nitrogen Balance
An individual’s 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
1) In balance
Nitrogen intake = nitrogen excretion
Dietary amino acids, nucleotides etc.
Urine, faeces, hair and skin loss, perspiration
2) Positive
Nitrogen intake > nitrogen excretion
Possible causes:
Childhood and adolescent growth
Pregnancy
Body building
3) Negative
Nitrogen intake < nitrogen excretion
Possible causes:
Illness
Starvation
Post-surgery
Amino acids are the major source of dietary N
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 -amino groups removed
Deamination of amino acids
Deamination generates:
a carbon skeleton a free amino group
can be used for anabolic or catabolic reactions
generally excreted
Some amino acids can be directly deaminated
Serine, threonine and glutamate can be directly deaminated
Glutamate deamination is catalysed by glutamate dehydrogenase (GDH)
glutamate + NAD(P)+ + H2O -ketoglutarate + NH4+ +
NAD(P)H
GDH
Glutamine can be deaminated in a two step process
glutamine + H2O glutamate + NH3
glutaminase
Glutamate is then deaminated by GDH
Glutamine can also be synthesised from glutamate
Glutamine synthesis is an energy requiring reaction
The reaction is catalysed by glutamine synthetase (GS)
glutamate + NH4+ + ATP glutamine +
ADP + Pi
GS
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
- ketoglutarate
oxaloaceatate
pyruvate
CAC
Addition of amino groups to these keto acids generates amino acids
Most amino acids are deaminated by donating their -amino acids to one of these keto acids
- ketoglutarate
oxaloacetate
pyruvate
glutamate
aspartate
alanine
Thus the deamination of most amino acids leads to the production of either glu, asp, ala or gln.
An example transamination
glutamate -KG -amino acid-keto acid
glutamate aminotransferase
Pyridoxal phosphate
Derived from vitamin B6
Takes part in all amino transferase reactions
Forms a Schiff base intermediate with substrates
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
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
glutamate + NH4+ + ATP glutamine +
ADP + Pi
The neurotransmitter GABA is inactivated by deamination
GS
GDH-ketoglutarate + NH4
+ + NADPH glutamate + NADP+ + H2O
However when ammonia concentrations are high:
Free ammonia is also produced in muscle
Amino groups can be liberated:
during normal muscle turnover
during starvation
during severe muscle activity
ATP ADP + Pi
2ADP ATP + AMP
AMP IMP + NH4+
AMP deamina
se
Pyruvate is usually abundant in active muscle
Muscle uses pyruvate as an acceptor keto acid
glutamate + pyruvate -ketoglutarate + alanine
alanine aminotransferase
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
AMP
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
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