Urea Cycle (Jenney)

Question 1

What are 2 pathways that result in glutamate?

Answer 1

NH4+ + alpha-ketoglutamate (glutamate dehydrogenase)

Glutamine + alpha-ketoglutarate (glutamate synthase)

Question 2

What molecule is a nitrogen carrier?

Answer 2

Glutamine

Question 3

What is the pathway for glutamine synthesis?

Answer 3

Glutamate + NH3 (glutamine synthetase)

Question 4

What is the major gluconeogenic amino acid?

Answer 4

Alanine

Question 5

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

Answer 5

N - urea & ketone bodies. C - glucose.

Question 6

Where is alanine processed in the body?

Answer 6

The liver

Question 7

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

Answer 7

Transamination

Question 8

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

Answer 8

NH4+

Question 9

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

Answer 9

NH3

Question 10

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

Answer 10

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

Question 11

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

Answer 11

Brain, muscle, gut

Question 12

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?

Answer 12

Fumarate from aspartate in the purine nucleotide cycle.

Question 13

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

Answer 13

Breakdown of various amino acids.

Question 14

Define transamination.

Answer 14

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

Question 15

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

Answer 15

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

Question 16

Transamination reactions are reversible. Is this true?

Answer 16

Yes

Question 17

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

Answer 17

Pyridoxal phosphate (PLP) - transaminase or aminotransferase enzyme

Question 18

Transamination reactions generate what 2 molecules in amino acid catabolism?

Answer 18

Glutamate or aspartate

Question 19

What amino acids are essential to humans?

Answer 19

PVT TIM HALL

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

Question 20

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

Answer 20

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

Question 21

What are the branched amino acids?

Answer 21

leucine, valine, isoleucine

Question 22

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

Answer 22

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

Question 23

Do amino acids make products other than proteins?

Answer 23

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

Question 24

What is NO?

Answer 24

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

Question 25

What does NO do?

Answer 25

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

Question 26

How is NO Synthesized?

Answer 26

From arginine

Question 27

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

Answer 27

Kill neurons.

Question 28

What is the glucose/alanine cycle?

Answer 28

Exchange glucose and alanine between muscle and liver.

Question 29

What is the purpose of the glucose/alanine cycle?

Answer 29

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

Question 30

Amino acid degredation in the muscle leads to what?

Answer 30

The transfer of nitrogens to alpha-ketoglutarate and pyruvate.

Question 31

How is the urea cycle regulated?

Answer 31

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

Question 32

What is the basic mechanism of urea cycle regulation?

Answer 32

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.

Question 33

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

Answer 33

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

Question 34

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

Answer 34

High protein diet or prolonged fasting

Question 35

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

Answer 35

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

Question 36

What links urea to the TCA cycle?

Answer 36

Fumarate

Question 37

What are the 5 steps of the urea cycle?

Answer 37

1. Synthesis of carbamoyl phosphate 2. Production of arginine by the urea cycle 3,4. Conversion of citrulline to arginine 5. Cleavage of arginine to produce urea

Question 38

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

Answer 38

carbamoyl phosphate & citrulline

Question 39

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

Answer 39

arginine, urea, ornithine

Question 40

What is a metabolic emergency caused by ammonia?

Answer 40

Hyperammonemia

Question 41

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?

Answer 41

Glutamine

Question 42

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

Answer 42

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

Question 43

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

Answer 43

Elevated glutamine and ammonia levels in circulation

Question 44

What drugs can you use to help excrete excess nitrogen?

Answer 44

Benzoic acid and phenylbutyrate

Question 45

Explain the mechanisms of benzoic acid and phenylbutyrate.

Answer 45

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.