Met 2: Transamination/Urea Cycle

Question 1

What are the two inputs into the cyclic-part of the Urea cycle?

What is the output?

Answer 1

Input: Aspartate and free NH3 (as carbamoyl phosphate)

Output: urea

Question 2

Describe how AA’s in the liver get rid of their NH3

Answer 2

1. AA donates its nitrogen group to alpha-ketoglutarate
   
   • AA remnant is alpha-ketoacid
   • Catalyzed by ALT
2. This produces glutamate

Question 3

What are the two possible fates for glutamate in the urea cycle?

How does each occur?

Answer 3

1. Glutamate can donate its N group to OAA to make aspartate
   
   • catalyzed by AST
   • glutamate remnant is alpha-ketoglutarate
2. Glutamate can be degraded by glutamate dehydrogenase
   
   • releases NH3 and alpha-ketoglutarate

Question 4

How does free NH3 end up in the urea cycle?

What are the enzymes and inputs for each step?

Answer 4

1. NH3 is converted to carbamoyl phosphate
   
   • by carbomyl phosphate synthase 1
   • Requires CO2 and ATP
2. Carbamoyl pohsphate is converted to citrulline
   
   • by ornithine transcarbamylase
   • requires ornithine
3. Citrulline can enter urea cycle

Question 5

Removal of NH3 from glutamate yields ______

Answer 5

Removal of NH3 from glutamate yields alpha-ketoglutarate

Question 6

What three enzymes are regulated in the urea cycle?

Answer 6

1. AST/ALT (transaminases)
2. CPS-1
3. Glutamate dehydrogenase

Question 7

What is the function of AST/ALT?

How is it regulated?

Answer 7

• AST and ALT both transfer an amino group.
  
  • ALT creats glutamate
  • AST creates aspartate.
• These enzymes are bidirectional, so regulation is based on concentrations of substrate v product

Question 8

What is the function of glutamate dehydrogenase?

How is it regulated? (2)

Answer 8

• Glutamate dehydrogenase degrades glutamate into alpha ketoglutarate and free NH3
• Regulated by concentration of substrate v product
• Allosteric: ATP inhibits it, ADP activates it.

Question 9

Describe the reaction catalyzed by carbomyl phosphate synthase 1?

What are its inputs?

Answer 9

Carbomyl phosphate synthase 1 converts free ammonia into carbomyl phosphate

• this requires CO2 and ATP

Question 10

Describe the regulation of carbomyl phosphate synthase 1

Answer 10

• Carbomyl phosphate synthase 1 is activated by N-acetylglutamate
• N-acetylglutamate is produced by N-acetylglutamate synthase
  
  • This occurs when there’s lots of Arg, acetyl-coA, or glutamate

Question 11

Name 2 molecules that transport nitrogen in the blood.

Where is each made?

Answer 11

• Alanine transports NH3 from muscle
• Glutamine transports NH3 from other tissues

Question 12

How does muscle export its nitrogen?

Answer 12

• Glutamate donates its NH3 to pyruvate
  
  • glutamate remnant is alpha-ketoglutarate
  • catalyzed by ALT
• pyruvate becomes Alanine
• Alanine goes into bloodstream and to liver

Question 13

How do non-muscle tissues export their NH3?

Answer 13

• Glutamate takes on another NH3 and becomes glutamine
  
  • catalyzed by glutamine synthetase
• Glutamine travels in blood to liver

Question 14

What happens to glutamine and alanine once they reach the liver?

Answer 14

They both become glutamate

Question 15

What is a ketogenic v glucogenic AA?

Answer 15

Ketogenic AA: cannot give net production of glucose

• Go into TCA cycle as acetyl-coA

Glucogenic AA: Can give net production of glucose

Question 16

Name 2 derivatives of arginine and their functions

Answer 16

Arginine creates

• NO (vasodilation)
• creatine phosphate (energy storage in muscles)

If you’re going to argue, there’s NO CRying Permitted

Question 17

Where does the urea cycle take place?

Answer 17

• Conversion of free ammonia to carbamoyl phosphate and then into citrulline occurs in mitochondria
• All else occurs in cytoplasm

Question 18

What is the function of the urea cycle?

Answer 18

Convert a toxic metabolic (NH3) into a less toxic metabolic (urea) for excretion