1. 1 25.6 Digestion of Proteins 25.7 Degradation of Amino Acids 25.8 Urea Cycle Chapter 25 Metabolic Pathways for Lipids and Amino Acids

2. 2 Proteins in the Body Proteins provide: Amino acids for protein synthesis. Nitrogen atoms for nitrogen-containing compounds. Energy when carbohydrate and lipid resources are not available.

3. 3 Digestion of Proteins

4. 4 Transamination In transamination: Amino acids are degraded in the liver. An amino group is transferred from an amino acid to an  -keto acid, usually  -ketoglutarate. The reaction is catalyzed by a transaminase or aminotransferase. A new amino acid, usually glutamate, and a new  -keto acid are formed.

5. 5 A Transamination Reaction NH 3 + O Alanine | || aminotransferase CH 3 —CH—COO - + - OOC—C—CH 2 —CH 2 —COO - Alanine  -Ketoglutarate O NH 3 + || | CH 3 —C—COO - + - OOC—CH—CH 2 —CH 2 —COO - Pyruvate Glutamate

6. 6 Oxidative Deamination Oxidative deamination: Removes the amino group as an ammonium ion from glutamate. Provides  -ketoglutarate for transamination. NH 3 + Glutamate | dehydrogenase - OOC—CH—CH 2 —CH 2 —COO - + NAD + + H 2 O Glutamate O || - OOC—C—CH 2 —CH 2 —COO - + NH 4 + + NADH  -Ketoglutarate

7. 7 Urea Cycle The urea cycle: Detoxifies ammonium ion from amino acid degradation. Converts ammonium ion to urea in the liver. O || H 2 N—C—NH 2 urea Provides 25-30 g urea daily for urine formation in the kidneys.

8. 8 Carbamoyl Phosphate In the mitochondria, an ammonium ion reacts with CO 2 from the citric acid cycle, 2 ATP, and water. NH 4 + + CO 2 + 2ATP + H 2 O O O || || H 2 N—C—O—P—O - + 2ADP + P i | O - Carbamoyl phosphate

9. 9 Reaction 1 Transfer of Carbamoyl Group The carbamoyl group is transferred to ornithine to form citrulline. Citrulline moves across the mitochondrial membrane into the cytosol.

10. 10 Reaction 2 Condensation with Aspartate In the cytosol, citrulline combines with aspartate. Hydrolysis of ATP to AMP provides energy. The N in aspartate is part of urea. Cytosol

11. 11 Reaction 3 Cleavage of Fumarate Fumarate: Is cleaved from argininosuccinate. Enters the citric acid cycle.

12. 12 Reaction 4 Hydrolysis Forms Urea Hydrolysis of arginine: Forms urea. Forms ornithine, which returns to the mitochondrion to pick up another carbamoyl group to repeat the urea cycle.

13. 13 Urea Cycle

14. 14 Summary of Urea Cycle The urea cycle converts: Ammonium ion to urea Aspartate to Fumarate 3ATP to 2ADP, AMP, 4P i NH 4 + + CO 2 + 3ATP + Aspartate + 2H 2 O Urea + 2ADP + AMP + 4P i + Fumarate