Lecture Slides for Nitrogen Metabolism

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Transcript Lecture Slides for Nitrogen Metabolism

Nitrogen Metabolism

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Sources of Nitrogen

• Atmospheric N 2 • NO 3 from lightning and rainfall 20 - 3

Haber Process (same Haber as in chemical warfare) Copyright  2013 Pearson Canada Inc.

High temperature, high pressure, catalyst 1 - 4

• Nitrogen-fixing bacteria convert N 2

Rhizobium

in plant root nodules •

Azotobacter

•

Klebsiella

• Some cyanobacteria to ammonia • Enzymes require anaerobic conditions.

• Root nodules contain leghemoglobin (i.e. legume hemoglobin).

• Ties up O 2 and passes to respiration.

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Nitrogenase N 2 + 8H + + 8 e + 16ATP (Requires a lot ⇄ 2NH 3 + H 2 of energy.) + 16 ADP • Dinitrogenase component (MoFe) reduces N 2 • Dinitrogenase reductase component (Fe) rereduces dinitrogenase 1 - 6

So how do we use the ammonia?

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:Production of Glutamate • Glutamate dehydrogenase • Reductive amination • Usually running backwards in critters due to low [NH 3 ] Copyright  2013 Pearson Canada Inc.

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

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Regulation Glutamine is involved in the metabolism of: • Aromatic a.a.s

• Several other a.a.s

• Purines • Pyrimidines • Amino sugars Regulated by feedback inhibition Also regulated globally by signal cascades • Adenylation of tyrosine blocks active site Copyright  2013 Pearson Canada Inc.

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Asparagine synthetase Copyright  2013 Pearson Canada Inc.

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Carbamoyl phosphate synthetase Carbamoyl phosphate can be made from both ammonia and glutamate Mitochondrial Cytosolic (Bacterial enzyme accepts both substrates) Copyright  2013 Pearson Canada Inc.

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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.

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Amino acid synthesis: OAA derivatives Copyright  2013 Pearson Canada Inc.

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Amino acid synthesis: Pyruvate derivatives Copyright  2013 Pearson Canada Inc.

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Amino acid synthesis: Ribose derivatives Copyright  2013 Pearson Canada Inc.

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Amino acid synthesis: Erythrose derivatives Copyright  2013 Pearson Canada Inc.

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Amino acid synthesis: a -ketoglutarate derivatives Copyright  2013 Pearson Canada Inc.

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Amino acid synthesis: 3-phosphoglycerate derivatives Copyright  2013 Pearson Canada Inc.

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Amino acid synthesis via transamination • You’ve seen this before.

 a -Amino groups of amino acids come by transamination from Glu • You can synthesize all amino acids from their a -keto conjugates.

• For the essential amino acids, we can’t produce the a keto acids.

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Also play a role in amino acid degradation • Above example is part of the degradation path for alanine.

• Transamination (transfer of the amide NH ketoglutarate) yields pyruvate.

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

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

• Glutamate is then deaminated by glutamate dehydrogenase.

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

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

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Removal of nitrogenous waste • Insects, birds, and reptiles primarily excrete • Oddly, so do dalmatians.

• Uric acid is pretty insoluble.

uric acid

• In humans, it is the end product of purine catabolism.

• Desert mammals like kangaroo rats primarily excrete uric acid.

• 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.

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Removal of nitrogenous waste – the urea cycle 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 20 - 28