Lecture 12 - Urea Cycle

Question 1

Urea is:

Answer 1

an excretory form of nitrogen

Question 2

each urea cycle allows for:

Answer 2

each cycle allows the excretion of 2 amines (NH2)

•Urea contains 2 amines (NH2) which enter the cycle at two points

•First is an NH4+ ion which is used to produce carbamoyl phosphate

•Second by Aspartate

Question 3

glutamate is an immediate source of:

Answer 3

aspartate & carbamoyl phosphate

Question 4

ammonium ion NH4+ ion is provided in:

Answer 4

the mitochondrial matrix

Question 5

_________ is an immediate source of ammonium ion for the Urea cycle

Answer 5

glutamate

Question 6

how is the ammonium (NH4) ion librated from glutamate?

Answer 6

NH4+ ion is liberated from Glutamate through the activity of Glutamate dehydrogenase (GDH) - an example of direct deamination

Question 7

what amino acids can be directly delaminated?

Answer 7

glutamate, histidine, glycine & sterile can be directly deaminated

Question 8

what is NH4 used to produce in the mitochondrial membrane?

Answer 8

NH4+ ion is used to produce Carbamoyl phosphate in the mitochondrial membrane and enters the Urea cycle

Question 9

what is carbamoyl phosphate made from?

Answer 9

Carbamoyl phosphate is made from CO2 (HCO3-) and NH4+

Question 10

Glutamate is also a source of amine for the Urea cycle:

Answer 10

glutamate provides the second amine entry into the urea cycle

•Glutamate can undergo transamination and donate the amine to oxaloacetate thereby giving aspartate

•The enzyme, Aspartate Aminotransferase are present at high levels in the liver to facilitate nitrogen remov

Question 11

summary of the urea cycle:

Answer 11

•Glutamate undergoes deamination releasing the amine as an ammonium ion (NH4+)

•Ammonium ion combines with bicarbonate ion (HCO3-) to give carbamoyl phosphate
- HCO3- is the result of CO2 production by TCA cycle
•Glutamate also undergoes transamination and donate the amine to oxaloacetate thereby giving Aspartate

Question 12

urea ATP economy:

Answer 12

urea cycle costs 3 ATP per urea

Question 13

overall chemical reaction for the urea cycle:

Answer 13

CO2 + NH4+ + 3 ATP + aspartate + 2 H2O  urea + 2ADP + Pi + AMP + PPi + fumarate

Question 14

what can amino acids be deaminated into?

Answer 14

amino acids can be deaminated into ammonia and their carbon skeleton

Question 15

what does glutamine synthetase do?

Answer 15

glutamine synthetase then uses a second ammonia ion to produce glutamine

Question 16

5 functions of the liver in protein metabolism:

Answer 16

1.Key site of amino acid catabolism where the carbon skeletons are recycled for gluconeogenesis to synthesise glucose

2.The site of citrulline production via urea cycle.

3.Synthesises fatty acids from glucose

4.Synthesises ketone bodies and secretes into the blood stream as a fuel for peripheral tissues

5.Major site for metabolism of drugs and toxic substances

Question 17

Functions of the Kidney in protein metabolism:

Answer 17

1.Excretes urea produced by the liver

2.Metabolises glutamine and ammonia to excrete nitrogen in a system *complementary to the liver

3.Only other organ next to the liver that can use gluconeogenesis to produce glucose

4.Absorbs the major plasma protein, albumin which is then broken down into amino acids

5.Major site of arginine synthesis from citrulline, which is an intermediate produced by the excretion of nitrogen (urea cycle)

Question 18

what do amino acids rely on and what can it cause if this reliance doesn’t work:

Answer 18

•For their absorption, and transport into our cells around the body amino acids rely on specific transporters

•Defects in these transporters are often implicated in disease

Question 19

Urea cycle:

Answer 19

•Once in the liver or kidney ammonia/nitrogen is metabolised through the urea cycle

•Glutamine, Glutamate and Aspartate provide the 2 amines for urea synthesis

•Glutamate can provide both

•First through glutamate dehydrogenase activity producing Carbamoyl phosphate

•CO2 for this reaction comes from the TCA cycle

•The 2nd through transamination into Aspartate

•Aspartate can also directly donate

•Defects in urea cycle enzymes can have catastrophic effects