BIOC Lecture 8: Nitrogen III Flashcards

1
Q

Is ammonia toxic?

A

Yes

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2
Q

Where is urea synthesised?

A

In the liver

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3
Q

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

A

Alanine and glutamine from other tissues

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4
Q

Why is portal blood high in NH3?

A

GI absorption from bacterial metabolism

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5
Q

Is urea toxic?

A

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

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6
Q

Urea vs ammonia solubility

A

Urea = soluble
Ammonia = non-soluble

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7
Q

Where is urea excreted?

A

Transported in blood to kidney for excretion

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8
Q

What does urea allow for the elimination of?

A

2 nitrogens

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9
Q

What is carbamoyl phosphate?

A

A high energy intermediate compound synthesised from bicarbonate and ammonia

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10
Q

Where does the ammonia in carbamoyl phosphate come from?

A

deamination of glutamine and glutamate

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11
Q

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

A

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

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12
Q

What is the carbamoyl phosphate reaction catalysed by?

A

Carbamoyl phosphate synthetase (CPS)

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13
Q

How does the carbamoyl phosphate reaction happen?

A

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

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14
Q

How is aspartate generated?

A

By transamination of glutamate and oxaloacetate

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15
Q

Where does the urea cycle occur?

A

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

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16
Q

What is the purpose of the urea cycle?

A

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

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17
Q

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

A

Carbamoyl Phosphate Synthase activity

18
Q

When is the urea cycle upregulated?

A

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

19
Q

When can urea cycle activity be reduced?

A

With liver disease i.e. cirrhosis

20
Q

How is carbamoyl phosphate synthase (CPS) regulated?

A

Allosterically regulated

21
Q

What is allosteric regulation?

A

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

22
Q

What molecule regulates CPS?

A

N-acetylglutamate

23
Q

How does N-acetylglutamate (NAG) regulate CPS?

A

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

24
Q

How is N-acetylglutamate made?

A

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

25
Q

What characteristics do disorders of urea cycle enzymes have?

A

Variety of phenotypes - mainly neurological and all involve hyperammonemia

26
Q

How are disorders of urea cycle enzymes treated?

A
  • By dietary modification (decrease protein)
  • Treat with amino acid-binding compounds
27
Q

What is the most common urea cycle enzyme defect?

A

The OTC enzyme (step 2)

28
Q

What is OTC?

A

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

29
Q

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

A

carbamoyl phosphate and ornithine to citrulline

30
Q

How does the diagnosis of OTC defect range?

A

severe neonatal-onset forms to milder late-onset forms

31
Q

What can NH4+ inhibit?

A

post-synaptic potentials

32
Q

What do depletion of CAC intermediates cause?

A

Decreased ATP for brain function

33
Q

What can ammonia toxicity in the brain lead to?

A

Swelling in brain cells

34
Q

Why do brain cells swell?

A

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

35
Q

Ammonia toxicity in the brain causes inappropriate levels of what?

A

Neurotransmitters, GABA, glutamate, aspartate

36
Q

What is the main nitrogen excretion product?

A

Urea

37
Q

Other than urea, what is excreting in the kidney?

A

Ammonia NH4+

38
Q

How is ammonia produced in the kidney?

A

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

39
Q

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

A

metabolic acidosis

40
Q

What is metabolic acidosis?

A

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

41
Q

What is crucial in the bodies reaction to acidosis?

A

Glutaminase

42
Q

How does glutaminase stop acidosis?

A

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