BIOC Lecture 8: Nitrogen III

Question 1

Is ammonia toxic?

Answer 1

Yes

Question 2

Where is urea synthesised?

Answer 2

In the liver

Question 3

What does the liver take up excess NH3 in the form of?

Answer 3

Alanine and glutamine from other tissues

Question 4

Why is portal blood high in NH3?

Answer 4

GI absorption from bacterial metabolism

Question 5

Is urea toxic?

Answer 5

No, it maintains N in a soluble non-toxic form

Question 6

Urea vs ammonia solubility

Answer 6

Urea = soluble
Ammonia = non-soluble

Question 7

Where is urea excreted?

Answer 7

Transported in blood to kidney for excretion

Question 8

What does urea allow for the elimination of?

Answer 8

2 nitrogens

Question 9

What is carbamoyl phosphate?

Answer 9

A high energy intermediate compound synthesised from bicarbonate and ammonia

Question 10

Where does the ammonia in carbamoyl phosphate come from?

Answer 10

deamination of glutamine and glutamate

Question 11

What does carbamoyl phosphate have to do with the urea cycle?

Answer 11

the first committed step in the urea cycle and serves as a critical nitrogen carrier that initiates the cycle

Question 12

What is the carbamoyl phosphate reaction catalysed by?

Answer 12

Carbamoyl phosphate synthetase (CPS)

Question 13

How does the carbamoyl phosphate reaction happen?

Answer 13

The enzyme CPS catalyzes the reaction where ammonia, carbon dioxide, and 2ATP combine to form carbamoyl phosphate

Question 14

How is aspartate generated?

Answer 14

By transamination of glutamate and oxaloacetate

Question 15

Where does the urea cycle occur?

Answer 15

First stage (steps 1 and 2) happens in the mitochondria
The rest of the cycle occurs in the cytoplasm/cytosol

Question 16

What is the purpose of the urea cycle?

Answer 16

essential for nitrogen balance and detoxification in the body, converting potentially harmful ammonia into urea for safe excretion

Question 17

What is the main point of regulation of the urea cycle?

Answer 17

Carbamoyl Phosphate Synthase activity

Question 18

When is the urea cycle upregulated?

Answer 18

In conditions where there needs to be a high metabolism of amino acids also under starvation conditions

Question 19

When can urea cycle activity be reduced?

Answer 19

With liver disease i.e. cirrhosis

Question 20

How is carbamoyl phosphate synthase (CPS) regulated?

Answer 20

Allosterically regulated

Question 21

What is allosteric regulation?

Answer 21

a protein’s function at one site is affected by the binding of a regulatory molecule to a separate, distinct site on the same protein

Question 22

What molecule regulates CPS?

Answer 22

N-acetylglutamate

Question 23

How does N-acetylglutamate (NAG) regulate CPS?

Answer 23

NAG binds allosterically to CPS I, enhancing its affinity for ATP and bicarbonate, thereby increasing its activity

Question 24

How is N-acetylglutamate made?

Answer 24

from acetyl-CoA and glutamate in a reaction catalyzed by the enzyme N-acetylglutamate synthase (NAGS)

Question 25

What characteristics do disorders of urea cycle enzymes have?

Answer 25

Variety of phenotypes - mainly neurological and all involve hyperammonemia

Question 26

How are disorders of urea cycle enzymes treated?

Answer 26

- By dietary modification (decrease protein) - Treat with amino acid-binding compounds

Question 27

What is the most common urea cycle enzyme defect?

Answer 27

The OTC enzyme (step 2)

Question 28

What is OTC?

Answer 28

Ornithine transcarbamylase (OTC) is an enzyme located in the mitochondria of liver cells. It catalyzes the second step of the urea cycle

Question 29

What conversion happens during the 2nd stage of the urea cycle?

Answer 29

carbamoyl phosphate and ornithine to citrulline

Question 30

How does the diagnosis of OTC defect range?

Answer 30

severe neonatal-onset forms to milder late-onset forms

Question 31

What can NH4+ inhibit?

Answer 31

post-synaptic potentials

Question 32

What do depletion of CAC intermediates cause?

Answer 32

Decreased ATP for brain function

Question 33

What can ammonia toxicity in the brain lead to?

Answer 33

Swelling in brain cells

Question 34

Why do brain cells swell?

Answer 34

Accumulation of glutamine in astrocytes increases osmotic pressure in the cerebral oedema

Question 35

Ammonia toxicity in the brain causes inappropriate levels of what?

Answer 35

Neurotransmitters, GABA, glutamate, aspartate

Question 36

What is the main nitrogen excretion product?

Answer 36

Urea

Question 37

Other than urea, what is excreting in the kidney?

Answer 37

Ammonia NH4+

Question 38

How is ammonia produced in the kidney?

Answer 38

By deamination of glutamine - reduces body acidity because the process removes protons

Question 39

The metabolism of epithelial cells of kidney proximal tubules is designed to compensate for what?

Answer 39

metabolic acidosis

Question 40

What is metabolic acidosis?

Answer 40

a decrease in blood pH due to an excess of acid or loss of bicarbonate

Question 41

What is crucial in the bodies reaction to acidosis?

Answer 41

Glutaminase

Question 42

How does glutaminase stop acidosis?

Answer 42

By converting glutamine to glutamate and ammonia, glutaminase facilitates the excretion of hydrogen ions as ammonium and indirectly contributes to bicarbonate production