Protein Catabolism
High-Yield Summary
- Protein becomes a significant fuel source only during prolonged fasting, after fat and ketone bodies are already mobilized.
- Proteolysis: pepsin (stomach) starts digestion; trypsin, chymotrypsin, carboxypeptidases A/B (pancreas, small intestine) finish it, yielding free amino acids absorbed via sodium/hydrogen-gradient active transport.
- Amino nitrogen can't be oxidized directly — transamination/deamination (aminotransferases, PLP/vitamin B6-dependent) remove the amino group from the carbon skeleton first.
- The urea cycle (liver) converts toxic ammonia into urea, excreted by the kidneys.
- Remaining carbon skeletons are glucogenic (→ glucose via glycolysis/TCA intermediates), ketogenic (→ acetyl-CoA/acetoacetate → ketone bodies; leucine and lysine are the ONLY exclusively ketogenic amino acids), or both.
Key Terms
- Proteolysis
- Breakdown of proteins into amino acids, starting with pepsin, continuing with pancreatic proteases.
- Transamination
- Transfer of an amino group from one molecule to another, via PLP-dependent aminotransferases.
- Deamination
- Removal of an amino group, releasing free ammonia.
- Urea cycle
- Liver pathway converting toxic ammonia into urea for kidney excretion.
Protein Catabolism Pathway
- 1Pepsin (stomach) partially digests protein
- 2Trypsin, chymotrypsin, carboxypeptidases A/B (small intestine) break proteins into peptides/amino acids
- 3Amino acids absorbed via sodium/hydrogen-gradient active transport
- 4Transamination/deamination (PLP-dependent) removes the amino group from the carbon skeleton
- 5Ammonia → urea (urea cycle, liver) → kidneys → excreted in urine
- 6Carbon skeleton → glycolysis/TCA intermediates (glucogenic) or acetyl-CoA/acetoacetate (ketogenic)
Glucogenic vs. Ketogenic Amino Acids
| Classification | Carbon Skeleton Fate / Example |
|---|---|
| Glucogenic | Glycolysis/TCA intermediates → glucose / Most amino acids |
| Ketogenic (exclusively) | Acetyl-CoA or acetoacetate → ketone bodies / Leucine, lysine |
| Both | Contributes to glucose AND ketone bodies / A small subset |
Common MCAT Trap
- Leucine and lysine are the ONLY amino acids that are exclusively ketogenic — every other amino acid is at least partly glucogenic.
- Nitrogen removal (transamination/deamination) must happen BEFORE the carbon skeleton can be used for energy — nitrogen itself is never oxidized for ATP.
- PLP (pyridoxal phosphate) is the active form of vitamin B6 — a common cofactor-identification trap on the MCAT.
Quick Recall
Which two amino acids are exclusively ketogenic?
What vitamin does PLP derive from?
What does the urea cycle accomplish?
When does the body significantly rely on protein catabolism for energy?