Amino Acid Metabolism and the Urea Cycle

How to Get Rid of the Amine?

• Amine groups are removed from amino acids by transferring them to alpha-ketoglutarate, generating glutamate.
• This process allows the amino acid to enter the urea cycle with another molecule.

Breakdown to NH₄⁺: 19 Amino Acids

• 19 amino acids break down to NH₄⁺.

Breakdown to NH₄⁺: Alanine (a Special Case)

• Alanine is broken down to pyruvate, which can be converted to glucose through gluconeogenesis or used to generate energy.
• Alanine is a breakdown product from muscles during exercise, which can then be used to make more pyruvate.

Breakdown to NH₄⁺: Glucose-Alanine Cycle

• Rapidly contracting muscle generates excess pyruvate and NH₂⁺.
• Pyruvate is converted to alanine by amino-transferase.
• Alanine is transported to the liver, where it is converted back to pyruvate.
• Pyruvate is then converted to glucose through gluconeogenesis.
• Glucose is transported back to the muscle for glycolysis to generate energy.

Urea Cycle

• The amino group is added to alpha-ketoglutarate to generate glutamate.
• The reverse reaction can be done to get glutamate back.
• Glutamate is used to shuttle the amino group around.
• The first step of the urea cycle is generating carbamoyl phosphate.
• This process requires energy.

Kreb Cycle

• Glucogenic amino acids can enter the TCA cycle directly.
• Ketogenic amino acids do not have to go through the same process.

Glycolysis: Preparatory and Pay-off

• Glucose is converted to glyceraldehyde 3-phosphate.
• Glucose 6-phosphate is converted to 1,3-bisphosphoglycerate.
• Fructose 6-phosphate is converted to 3-phosphoglycerate.
• Fructose 1,6-bisphosphate is converted to 2-phosphoglycerate.
• Glyceraldehyde 3-phosphate is converted to phosphoenolpyruvate.
• Dihydroxyacetone phosphate is converted to pyruvate.

Enzymes/Delta G

• Oxidoreductases transfer electrons via oxidation or reduction.
• Transferases transfer chemical groups from one molecule to another.
• Hydrolases cleave a substrate using water.
• Lyases add groups to double bonds or form double bonds by removing groups.
• Isomerases rearrange a single substrate, generating isoforms.
• Ligases join two substrates, often by eliminating water.

Urea Cycle (continued)

• The first step is ornithine to citrulline, which generates ornithosuccinate.
• Aspartate is made from oxoacetate in the TCA cycle.
• Aspartate is used to funnel into the urea cycle.
• The final step generates the starting product, with one amino group coming from the amino acids and the other from aspartate.