Urea cycle and nitrogen metabolism

which two metabolic cycles link together in land mammals?

• kreb’s cycle and urea cycle

which two metabolic cycles don’t link together in birds and terrestrial reptiles?

• kreb’s cycle and uric acid cycle

what is the general process of urea and nitrogen metabolism?

1. intracellular proteins → amino acids → a-ketoacids and NH4+

2. NH4+ → biosynthesis of AAs or urea/uric cycle

3. a-keto acids → kreb’s cycle

after deamination of amino acids, what happens to the ammonium formed?

1. either excreted - fish and amphibians

2. a-ketoacids enter kreb’s cycle

In fish:

1. what is N excreted as

2. where is it synthesised

3. where is it transported to

4. via what?

5. excreted through?

1. ammonotelic (ammonium)

2. liver

3. n/a

4. n/a

5. gill

In most land mammals:

1. what is N excreted as

2. where is it synthesised

3. where is it transported to

4. via what?

5. excreted through?

1. ureoteilc (urea)

2. liver

3. kidney

4. blood

5. bladder → urethra

in birds/reptiles:

1. what is N excreted as

2. where is it synthesised

3. where is it transported to

4. via what?

5. excreted through?

1. uricotelic (uric acid)

2. liver

3. kidney

4. blood

5. cloaca

Compare the energy cost to excrete N in fish, land mammals, birds and reptiles

• least amount of energy in fish, excrete as NH4+/NH3

• most in reptiles as uric acid

in terms of water needed for N excretion, compare between fish, most land animals and birds/reptiles

1. birds/reptiles take the least, secreting as uric acid

2. fish require the most, secreting as ammonium

what are 2 pathways that cause excess N in the body?

1. digestion/breakdown of diet proteins

2. breakdown of skeletal muscle proteins

why must amino acids be deaminated?

• they can’t be stored in the body or excreted in their normal form.

what is the process of deamination?

• amino acids → a-keto acids and NH4+

what enzymes are involved in deamination?

• transaminase

  • glutamate dehydrogenase

what is transaminase involved in?

• a-amino acid → a-keto acid

• simultaneously a-ketoglutarate → glutamate

what is glutamate dehydrogenase involved in?

• glutamate → a-ketoglutarate

• simultaneously NAD + H2O → NADH + NH4+

how can we remove excess ammonia if we don’t have amino acids present?

• a-ketoglutarate → glutamate → glutamine

• each step requires NH4+

what is the carbonated skeleton of an amino acid?

• the a-ketoacid

what is the fate of the carbonated cytoskeleton of an aa?

• go down 20 different pathways, converge on 7 metabolic intermediates that feed Kreb’s cycle

which essential amino acids are glucogenic amino acids (8)

1. methionine

2. arginine

3. histidine

4. threonine

5. isoleucine

6. phenylalanine

7. tryptophan

8. valine

what is a glucogenic aa?

• they enter into the Kreb’s cycle components/form pyruvate → glucose synthesis

what are the 5 essential ketogenic aas?

1. leucine

2. lysine

3. isoleucine

4. phenylalanine

5. tryptophan

what are ketogenic aas?

• form acetyl-CoA/acetoacetate

• formation of lipids

what is an essential aminoacid?

• the organism can’t synthesise the carbon skeleton themselves, must be obtained via the diet

5 enzymes involved in ammonium catabolism

1. carbamoyl synthetase

2. ornithine transcarbamolyase

3. none - only ATP

4. arginosuccinase

5. arginase

what is hte energy expenditure for ammonium breakdown?

• 2ATP/N

where in the cell do the two parts of urea metabolism take place?

• mitochondria

• ctyosol

where do some of the products of the nitric cycle go?

• TCA/citric/Kreb’s cycle

how does uric acid formation in birds differ from urea formation

• uric acid is produced

• requires more energy - 3.75ATP/N atom

what is the IN of nitrogen balance?

• total intake of organic nitrogen

what is the EX of nitrogen balance

• total excretion of organic nitrogen

if IN = EX what does this mean for nitrogen balance?

• nitrogen IN and EX is balanced

if IN > EX, what does this mean?

• positive nitrogen balance = growth/repair

if IN < EX, what does this mean?

• negative nitrogen balance e.g. fasting/starvation/constant/protein turnover

what is the cahill cycle

• the production of urea from skeletal muscle breakdown → amino acid → energy production in the liver

what is the Cori cycle?

• anaerobic glycolysis and the relationship with skeletal muscle/blood/liver

outline the urea cycle

1. ornithine → citrulline (with energy from amino acids) → arginino-succinate (uses aspartate) → arginine (with loss of fumarate) → ornithine - this is where urea is lost with the addition of water

fumarate is produced in the urea cycle, what does this go on to do?

• uses water → malate → oxaloacetate → aspartate (which is used again in the urea cycle).

why is it key to understand that urea cycle and uric acid are cycles?

• products produced are recycled and used up again in the same cycle - consider the impact if the cycle goes wrong and the further consequences this’ll have.