19: Amino Acid Oxidation and Urea Cycle

Why does urea have to made?

Avoid circulating NH₃, highly reactive and causes pH problems in blood + disturbs brain function

When are amino acids used as fuel

• not needed for new protein synthesis

• during starvation when carbohydrates unavailable

Alpha-keto acids

amino acids where amine group has been removed

key amino acids transported/delivered for deamination in the liver

• glutamine

• glutamate

• alanine

enzymes that move amino groups between different carbon skeletons

aminotransferase

main molecule(s) responsible for transporting ammonia in the blood

glutamine, alanine

Alanine vs glutamine

Since alanine = 3C molecule, lose less carbon by transporting it from muscle compared to glutamine

amino acids that end up as TCA intermediates that can contribute Cs to synthesis of glucose

glucogenic amino acids

amino acids that end up as ketone bodies

ketogenic amino acids

Strictly ketogenic amino acids

• Lysine

• Leucine

urea structure benefits

• 2 amines and 1 carbon —> gets rid of more amines and not a lot of carbons

• Well oxidized

2 nitrogens on urea from…

• aspartate

• carbamoyl phosphate

3 sets of ketoacids

• alpha-ketoglutarate to glutamate (5C)

• Alanine to pyruvate (3C)

• OAA to aspartate (4C)

ketoacids

Required to continue urea cycle

ornithine

non-protein amino acids in urea cycle

• ornithine

• citrulline

Arginosuccinate broken down to…

• Fumarate (TCA)

• Arginine (urea cycle)

Regulation of urea cycle

1. transcriptional regulation of genes for urea cycle enzyme (long-term changes responding to diet)

2. regulation of carbamoyl phosphate synthase I by N-acetylglutamate