Nitrogen Metabolism Copyright 2013 Pearson Canada Inc. 20 - 1

Nitrogen Metabolism

Copyright 2013 Pearson Canada Inc. 20 - 1


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Sources of Nitrogen• Atmospheric N2

• NO3- from lightning and rainfall

Haber Process (same Haber as in chemical warfare)


High temperature, high pressure, catalyst


Nitrogen-fixing bacteria convert N2 to ammonia•Rhizobium in plant root nodules•Azotobacter•Klebsiella•Some cyanobacteria

• Enzymes require anaerobic conditions.• Root nodules contain leghemoglobin (i.e.

legume hemoglobin).• Ties up O2 and passes to respiration.

Nitrogenase

• Dinitrogenase component (MoFe) reduces N2

• Dinitrogenase reductase component (Fe) rereduces dinitrogenase

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N2 + 8H+ + 8 e- + 16ATP ⇄ 2NH3 + H2 + 16 ADP(Requires a lot of energy.)


So how do we use the ammonia?

:Production of Glutamate

• Glutamate dehydrogenase

• Reductive amination

• Usually running backwards in critters due to low [NH3]


Glutamine synthetase


Glutamic acid, glutamine, and -ketoglutarate are primary players in moving nitrogens.

Regulation


Glutamine is involved in the metabolism of:•Aromatic a.a.s•Several other a.a.s•Purines•Pyrimidines•Amino sugars

Regulated by feedback inhibitionAlso regulated globally by signal cascades•Adenylation of tyrosine blocks active site

Asparagine synthetase


Carbamoyl phosphate synthetase


Mitochondrial

Cytosolic

(Bacterial enzyme accepts both substrates)

Carbamoyl phosphate can be made from both ammonia and glutamate

Amino acid metabolism


• Different organisms can make different sets of amino acids.• Those we can’t manufacture are essential amino acids in our diet.• Lists of essential and non-essential vary.

Amino acid synthesis: OAA derivatives


Amino acid synthesis: Pyruvate derivatives


Amino acid synthesis: Ribose derivatives


Amino acid synthesis: Erythrose derivatives


Amino acid synthesis: -ketoglutarate derivatives


Amino acid synthesis: 3-phosphoglycerate derivatives


Amino acid synthesis via transamination

• You’ve seen this before. -Amino groups of amino acids come by transamination

from Glu• You can synthesize all amino acids from their -keto

conjugates.• For the essential amino acids, we can’t produce the -

keto acids.Copyright 2013 Pearson Canada Inc. 1 - 20

Also play a role in amino acid degradation

• Above example is part of the degradation path for alanine.

• Transamination (transfer of the amide NH2 to -ketoglutarate) yields pyruvate.

• Pyruvate can be tossed into PDH and the Krebs cycle.


Amino acid oxidases

• The -amino group is usually removed by transfer to -ketoglutarate to yield glutamate and the -keto acid.

• Glutamate is then deaminated by glutamate dehydrogenase.

• There are also amino acid oxidases, using a flavin electron acceptor.



Fates of deaminated amino acids (i.e. fate of the carbons)

Removal of nitrogenous waste


• Insects, birds, and reptiles primarily excrete uric acid.• Desert mammals like kangaroo rats primarily excrete uric acid.• Oddly, so do dalmatians.• Uric acid is pretty insoluble.• In humans, it is the end product of purine catabolism.• Overproduction or underexcretion can lead to the formation of uric

acid crystals – frequently starting in the gravitationally lowest joints – i.e. the big toe.

• That condition is gout, which is often extremely painful.

Gout – a surgical example in the left hand


Removal of nitrogenous waste – the urea cycle

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The universal product of degrading amino acids is ammonia.•Ammonia is toxic at not very high concentrations.•You have to get rid of it.•If you are an aquatic organism, you can just diffuse in into the environment.•We convert ammonia to urea.The basic idea:•Add the nitrogens to ornithine to (eventually) make arginine.•Cleave the guanidino group off arginine to leave you with ornithine and urea.•Urinate out the urea.•Throw the ornithine back into the cycle.


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Ammonia transport to the liver• Urea formation takes place in the liver• Waste nitrogen is transported through the blood

as Gln or Ala.• Reconverted to ammonia in the liver

Documents

Nitrogen Metabolism Copyright 2013 Pearson Canada Inc. 20 - 1