Where amino acid carbon enters, and what it can become
Protein into everything
1
Scroll sideways to see the whole map.
Glucogenic: can become glucose Ketogenic: can only become fat or ketones Both, depending on the fragment Junction metabolite The one-way door
The only rule you needEverything that enters at or above pyruvate, or anywhere on the TCA cycle, can reach oxaloacetate and leave as glucose. Everything that enters as acetyl-CoA or acetoacetate cannot, because PDH and the two decarboxylations of the cycle are irreversible.
The two to memorizeLeucine and lysine are purely ketogenic — the only two of the twenty. Five more (isoleucine, phenylalanine, threonine, tryptophan, tyrosine) are both, because different parts of the same skeleton land in different places. The remaining thirteen are purely glucogenic.
Where the nitrogen goesThis map is only about carbon. The amino group is removed first, usually by transamination onto α-ketoglutarate to make glutamate, which then hands the nitrogen to the urea cycle. Carbon and nitrogen part company at the very first step.
An amino acid's fate is decided entirely by where its carbon skeleton lands. That is why no one memorizes twenty separate answers: you memorize six entry points, note that two amino acids are purely ketogenic, and derive the rest.
After losing its nitrogen, an amino acid’s carbon skeleton enters one of two fates:
Glucogenic: converted to pyruvate or a TCA cycle intermediate. Can be used to make glucose via gluconeogenesis.
Ketogenic: converted to acetyl-CoA or acetoacetate. CANNOT be used to make glucose (because acetyl-CoA cannot be converted back to pyruvate).
Most amino acids are purely glucogenic. A few are both. Only two are purely ketogenic.
Purely Ketogenic
Leucine (L)
Lysine (K)
Both Glucogenic and Ketogenic
Isoleucine (I)
Phenylalanine (F)
Threonine (T)
Tryptophan (W)
Tyrosine (Y)
Purely Glucogenic
All others (13 amino acids).
Entry Points into Central Metabolism
| Entry point | Amino acids |
|-------------|-------------|
| Pyruvate | Ala, Cys, Gly, Ser, Thr, Trp |
| Acetyl-CoA | Ile, Leu, Lys, Phe, Thr, Trp, Tyr |
| Alpha-KG | Arg, Gln, Glu, His, Pro |
| Succinyl-CoA | Ile, Met, Thr, Val |
| Fumarate | Asp, Phe, Tyr |
| Oxaloacetate | Asn, Asp |
You do not need to memorize these entry points for the MCAT, but know the glucogenic/ketogenic classification.
Which two amino acids are purely ketogenic?
Click to reveal answer
Leucine (L) and Lysine (K) - the two L’s. Both are catabolized only to acetyl-CoA and/or acetoacetate, which cannot be converted back to pyruvate and therefore cannot be used for gluconeogenesis. All other amino acids are either purely glucogenic or both.
Why cannot purely ketogenic amino acids contribute to net glucose production?
Click to reveal answer
Their carbon skeletons are broken down only to acetyl-CoA or acetoacetate. Acetyl-CoA cannot be converted back to pyruvate (the pyruvate dehydrogenase reaction is irreversible). Without entry to pyruvate or a TCA intermediate that connects to OAA, no net gluconeogenesis is possible. The only ultimate fate of the carbons is oxidation in the TCA cycle (if paired with OAA) or conversion to ketone bodies/cholesterol.
What are the five amino acids that are both glucogenic and ketogenic?
Click to reveal answer
Isoleucine, Phenylalanine, Threonine, Tryptophan, and Tyrosine. Their catabolism produces both pyruvate or TCA intermediates (glucogenic portion) and acetyl-CoA or acetoacetate (ketogenic portion). Memorize Leu and Lys as the only purely ketogenic; the rest is easier to reason about.
