Week 5: Nitrogen Management

Question 1

When does Transamination occur

Answer 1

Extended fasting because it is breaking down proteins which are the buidling blocks of life

Question 2

Cortisol effect o proteins

Answer 2

inhibit protein synthesis

Question 3

Transamination and cortisol

Answer 3

cortisol inhibits protein synthesis so more AAs are available for energy (oxidation)

Question 4

Transamination & urea cycle steps

Answer 4

AA + α-ketoglutarate –> α-ketoacid + glutamate (Transamination)

α-ketoacid further oxidized

Glutamate can be secreted into the blood or further processed into glutamine

Glutamate -glutamine synthase-> Glutamine (to process further ammonia)

Glutamate or Glutamine are taken up by the liver

In skeletal muscle:

Pyruvate -> Alanine (Transamination reaction (pyruvate is the α-ketoacid of alanine)) (*PArt of the alanine glucose cycle*)

Liver takes up alanine and undergoes transamination to convert alanine -Alanine Transaminase-> pyruvate to gluconeogenesis

Glutamine -glutaminase-> glutamate + NH4+

Glutamate + NAD+ -Glutamate DH-> + α-ketoglutarate + NADH + NH4+

α-ketoglutarate -TCA cycle-> or Transported into the cytoplasm

Free amonia is rapidly diffuseably so it needs to be traped very quickly

NH4+ + HCO3- -Carbamoyl phosphate synthase-> Carbamoyl phosphate

Carbamoyl phosphate + Ornithine -Ornithine Transcarbamylase-> Citrulline

Citrulline exits the mitochondria into the cytoplasm by citrulline-ornithine antiporter

Citrulline in the cytoplasm:

Citrulline + Aspartate -Argininosuccinate synthase-> Argininosuccinate

Argininosuccinate -Argininosuccinate Lyase-> Arginine + Fumarate

Arginine -Arginase-> Ornithine + Urea

Ornithine can be used in antiporter transport of citrulline and repeat cycle

Fumarate + H2O -Fumirase-> Malate

Malate + NAD+ -Malate DH-> Oxaloacetate + NADH

Oxaloacetate + Glutamate -Aspartate Transaminase-> Aspartate + α-ketoglutarate (Transamination tat restores #2 N donor)

Question 5

Ornithine Transcarbamylase mutation

Answer 5

urea cycle defects resulting in free ammonia and hyperammonemia

Question 6

Aspartate and urea

Answer 6

2nd N on urea from aspartate

Question 7

Carbamoyl phosphate and urea

Answer 7

Donates #1 nitrogen on urea from free ammonia

Question 8

Nitrogens in ammonia

Answer 8

1st N is from free ammonia from carbamoyl phosphate

2nd is from aspartate

Question 9

Liver tests

Answer 9

ALT

AST

Transaminase reactions

Question 10

Regulation of urea cycle

Answer 10

Completely regulated by substrate concentrations

Question 11

Urea Cycle speeds

Answer 11

mild fast - slowly

Prolonged fast - moves much faster

Question 12

What happens with defects in urea cycle enzymes?

Answer 12

Hyperaminemia (build-up of ammonia)

Question 13

Protein only diet

Answer 13

can saturate the urea cycle and cause hyperammonemia (build-up of ammonia)