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CMBM Exam 4 CL > Urea Cycle (Jenney) > Flashcards

Urea Cycle (Jenney) Flashcards

1
Q

What are 2 pathways that result in glutamate?

A

NH4+ + alpha-ketoglutamate (glutamate dehydrogenase)

Glutamine + alpha-ketoglutarate (glutamate synthase)

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2
Q

What molecule is a nitrogen carrier?

A

Glutamine

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3
Q

What is the pathway for glutamine synthesis?

A

Glutamate + NH3 (glutamine synthetase)

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4
Q

What is the major gluconeogenic amino acid?

A

Alanine

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5
Q

Alanine converts some of its atoms into specific compounds. Name the compounds as well as what was used to make them.

A

N - urea & ketone bodies. C - glucose.

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6
Q

Where is alanine processed in the body?

A

The liver

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7
Q

Glutamate collects nitrogen from other amino acids via what kind of reaction?

A

Transamination

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8
Q

At physiological pH are you more likely to find NH4+ or NH3?

A

NH4+

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9
Q

Which molecule can cross the cell membrane, NH4+ or NH3?

A

NH3

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10
Q

What are 3 major reactions regarding the fate of ammonium that occur in all cells?

A
  1. glutamate dehydrogenase/synthase
  2. glutamine synthetase
  3. carbamoyl-phosphate synthetase I
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11
Q

What 3 body parts provide sources of NH4 for the urea cycle?

A

Brain, muscle, gut

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12
Q

The brain and muscle both produce the same molecule that provides NH4 for the urea cycle. What is this molecule, and how is it produced?

A

Fumarate from aspartate in the purine nucleotide cycle.

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13
Q

The gut provides NH4 for the urea cycle via what molecule(s)?

A

Breakdown of various amino acids.

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14
Q

Define transamination.

A

Transfer of an amino group from an alpha-amino acid to an alpha-keto acid.

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15
Q

In amino acid biosynthesis, the ______ of ______ is transferred to various _____ acids generating _____ acids.

A

…..amino group…..glutamate…..alpha-keto…..alpha-amino…..

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16
Q

Transamination reactions are reversible. Is this true?

A

Yes

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17
Q

What cofactor is used for transamination reactions? What is it known as?

A

Pyridoxal phosphate (PLP) - transaminase or aminotransferase enzyme

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18
Q

Transamination reactions generate what 2 molecules in amino acid catabolism?

A

Glutamate or aspartate

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19
Q

What amino acids are essential to humans?

A

PVT TIM HALL

phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, alanine, lysine, leucine

20
Q

What is similar about the 3 branched chain amino acids regarding degredation?

A

Same 3 enzymes catalyze the 1st 3 steps in all pathways.

21
Q

What are the branched amino acids?

A

leucine, valine, isoleucine

22
Q

What is the basic mechanism for branched-chain amino acid degredation?

A

Branched AA —–> (br. chain AA transaminase) alpha-keto acid —–> (br. chain alpha-keto acid dehydrogenase) —–> Acetyl CoA or Succinyl CoA

23
Q

Do amino acids make products other than proteins?

A

Yes - glutathione, glycine, methionine, purines, bile salts, heme, creatine phosphate, etc.

24
Q

What is NO?

A

Nitric oxid -gas hormone which can diffuse rapidly in cells. It is also a messenger that activates gCMP synthesis.

25
Q

What does NO do?

A

Relaxes blood vessels, lowers BP, and is a neurotransmitter to the brain.

26
Q

How is NO Synthesized?

A

From arginine

27
Q

What happens when you have high levels of NO during a stroke?

A

Kill neurons.

28
Q

What is the glucose/alanine cycle?

A

Exchange glucose and alanine between muscle and liver.

29
Q

What is the purpose of the glucose/alanine cycle?

A

It provides an indirect means for muscle to eliminate N (and pyruvate, if necessary) and replenish its energy supply.

30
Q

Amino acid degredation in the muscle leads to what?

A

The transfer of nitrogens to alpha-ketoglutarate and pyruvate.

31
Q

How is the urea cycle regulated?

A

By substrate availability; this is a feed-forward regulation.

32
Q

What is the basic mechanism of urea cycle regulation?

A

The presence of arginine stimulates the synthesis of NAG (N-acetylglutamate), which activates CPSI (carbamoyl phosphate synthetase I), which pushes the urea cycle forward at a faster rate.

33
Q

What 2 reactions are stimulated by the increase of arginine levels in the liver?

A

Synthesis of NAG, and thus an increased rate at which carbamoyl phosphate is produced. Production of more ornithine, making the cycle operate more rapidly.

34
Q

To what conditions that require increased protein metabolism does the induction of urea cycle enzymes respond?

A

High protein diet or prolonged fasting

35
Q

What are the major enzymes of the urea cycle and where can they be found?

A

Mitochondrial matrix - CPSI, ornithine transcarbamoylase; cytosol - arginosuccinate synthetase, arginosuccinate lyase, arginase

36
Q

What links urea to the TCA cycle?

A

Fumarate

37
Q

What are the 5 steps of the urea cycle?

A
  1. Synthesis of carbamoyl phosphate
  2. Production of arginine by the urea cycle
    3,4. Conversion of citrulline to arginine
  3. Cleavage of arginine to produce urea
38
Q

What are the main products of the urea cycle that exist in the mitochondrial matrix?

A

carbamoyl phosphate & citrulline

39
Q

What are the main products of the urea cycle that exist in the cytosol?

A

arginine, urea, ornithine

40
Q

What is a metabolic emergency caused by ammonia?

A

Hyperammonemia

41
Q

When a urea cycle enzyme is defective, you get an accumulation of urea cycle intermediates. This causes levels of what molecule to increase in the circulation?

A

Glutamine

42
Q

If there’s not a enough glutamine, then what levels are also being decreased? What does this lead to?

A

Alpha-ketoglutarate levels are too low to fix more free ammonia, leading to elevated levels of ammonia in the blood.

43
Q

What would you expect to see if there are defects in any urea-cycle enzyme?

A

Elevated glutamine and ammonia levels in circulation

44
Q

What drugs can you use to help excrete excess nitrogen?

A

Benzoic acid and phenylbutyrate

45
Q

Explain the mechanisms of benzoic acid and phenylbutyrate.

A

Benzoic acid - after activation it reacts with glycine to form hippuric acid, which is excreted. Phenylbutyrate - oxidation product phenylacetate forms conjugate with glutamine and is excreted.

CMBM Exam 4 CL (17 decks)

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