Which amino acid is both glucogenic as well as ketogenic ?

A 54-year-old male who was diagnosed with HIV (human immuno deficiency virus) infection 2 years back, is currently in the terminal stage. He is now cachectic and having a difficult time obtaining any caloric intake yet he refuses to take a naso gastric or gastric feeding tube. Since his muscle and organs are metabolically active, which of the following amino acids will produce both glucose and ketone bodies as an energy source?

A. Alanine

B. Tyrosine

C. Proline

D. Glycine

E. Leucine

The correct answer is B- Tyrosine.

Amino acids can be classified based on their metabolic fate-

I) Purely glucogenic- There are 14 amino acids in this category

2) Purely ketogenic- Leucine and lysine

3) Both glucogenic as well as ketogenic- Phenyl alanine, Tyrosine, Tryptophan, and Isoleucine

Tyrosine upon metabolism produces one molecule of fumarate and one molecule of acetoacetate. Fumarate is a glucogenic component because it is a TCA cycle intermediate and gets converted to oxaloacetate, which is channeled towards the pathway of gluconeogenesis. Acetoacetate is cleaved to form Acetyl co A, a precursor of ketone bodies. Hence tyrosine is both glucogenic as well as ketogenic.

As regards other options- Alanine, proline and glycine are purely glucogenic whereas Leucine is purely ketogenic (Figure)


Figure- Showing the entry of metabolic products of amino acids into TCA cycle

Alanine produces pyruvate by transamination, which is a substrate for gluconeogenesis.

Proline forms glutamate that is converted to alpha ketoglutarate upon transamination or oxidative deamination. Alpha ketoglutarate is an intermediate of TCA cycle, hence it is glucogenic.  All the TCA cycle intermediates beyond Alpha glutarate are glucogenic in nature.

Glycine and serine are inter convertible. Serine forms pyruvate by non oxidative deamination, hence glucogenic.

Leucine forms Acetoacetyl co A (Figure), Hence it is purely ketogenic.


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