M4: Integrated Metabolism L28

Question 1

How can amino acids be utilized in the starving or fasting state?

Answer 1

Liver: Amino acids can serve to generate keto acids. The keto-acids can be used to generate ketone bodies to b e used as a source of ATP in other organs such as the brain and the heart.

Muscle: Proteins in the muscle can also be degraded when doing exercise and the amino acids will be transported back for detoxification in the liver.

Tissues: Other tissues may also degrade their proteins to generate amino acids that are transported back to the liver.

This depends on your metabolic state (fed or fasting state):
- In the fasting state you will start breaking down the amino acids (gluconeogenic and ketogenic) to generate energy.

a.a. breakdown is mostly done in the starving state after fasting.

Question 2

What happens to amino acid levels, glucose levels, and ketone body levels during starvation?

Answer 2

• Ketone bodies increase when you starve
• Glucose remains rather constant
• amino acids remain constant as well
  The pool of amino acids must remain constant in the body. Therefore when we eat, either we need to form proteins or we need to get rid of them by degradation..

Question 3

What disorders can be caused by the urea cycle?

Answer 3

Disorders
- Mutations found in all the enzymes (GDH, CPS1, NAGS, ASS, Arginosuccinase, Arginase, OTC)
and transporter ORNT1
- Mutations in the early steps of the cycle
have worst prognosis (CPS-1, OTC) - All lead to HyperAmmonemia.

Question 4

What are treatments for deficiencies in urea cycle enzymes?

Answer 4

1. Reducing protein intake
2. Stimulating alternative pathways of NH4+ excretion:

• 2 major ways of reducing NH4+ blood levels:
  a) Phenylbutyrate: Acquires glutamine (which has 2 ammonias) and converts it to a non toxic compound (phenylacetylglutamine) that will be excreted in the urine.
  b) Benzoate: Will acquire glycine which has 1 ammonia) to become Hippurate which is also excreted in urine.