Hepatic handling of ammonia

Question 1

amino acids action

Answer 1

cannot be stored directly
use for energy - remove amino group in transamination
aa+alpha ketoglutarate alpha keto acid + glutamate

Question 2

glutamate dehydrogenase action

Answer 2

removes NH2 from aa

glutamate -> alpha ketoglutarate

Question 3

ammonia production

Answer 3

generated in aa metabolism and excreted by the liver as urea and by the kidney as NH4+
free ammonia is very toxic

Question 4

urea cycle regulation

Answer 4

acute = control of carbamoyl-phosphate synthetase reaction, committed point of entry of ammonia. enzyme activated by N-acetylglutamate and also activated by ornithine/ammona
chronic = high protein intake induces more enzyme production

Question 5

urea cycle step 1

Answer 5

begins in mt of hepatocytes
rate limiting step
bicarbonate and ammonia -> carbamoyl phosphate by CPS1 enzyme

Question 6

urea cycle step 2

Answer 6

carbamoyl phosphate and ornithine -> citrulline
ornithine transcarbomylase
citrulline then transported from mt into cytosol

Question 7

urea cycle step 3

Answer 7

citrulline reacts with aspartate to form arginosuccinate

arginiosuccinate synthetase

Question 8

urea cycle step 4

Answer 8

arginosuccinate -> arginine and fumarate by arginosuccinate lyase
link to TCA

Question 9

urea cycle step 5

Answer 9

arginine undergoes hydrolysis via arginase to form urea and ornithine
ornithine regenerates for cycle to continue (waits for more carbamoyl phosphate to react)

Question 10

cerebral ammonia metabolism

Answer 10

NH3 can’t cross BBB
glutamine synthetase converts ammonia into glutamate and glutamine, when can then go to liver
astrocytes protect neurons from ammonia

Question 11

cerebral toxicity of ammonia

Answer 11

• ammonia increases resting potential
• casques lethargy, poor feeding, hypothermia, vomiting
• can get cerebral oedema, swollen astrocytes in cortex
• chronic = cerebral atrophy