A common intermediate of Urea and TCA cycle

Question of the day

Which one of the following can be converted to an intermediate of either the citric acid cycle or urea cycle?

A. Tyrosine

B. Lysine

C. Leucine

D. Tryptophan

E. Aspartate

Answer- The correct answer is- E -Aspartate.

1) Role of Aspartate in urea cycle

Aspartate participates in urea cycle for condensation with citrulline to form Argino succinic acid. The reaction is catalyzed by Argino succinic acid synthetase (Aspartate provides one out of the two nitrogens of urea, the other nitrogen is contributed by Glutamate).

In the subsequent reaction, Argino succinic acid undergoes a lytic reaction to form Arginine and fumarate. Fumarate forms a link between TCA cycle and urea cycle (figure-1). Fumarate can be recycled to form Oxaloacetate, through intermediate formation of malate that can be transaminated to form Aspartate, to get reutilized in the urea cycle (figure-1).

TCA and urea cycle link

Figure-1- Showing aspartate as a common intermediate of TCA cycle and Urea cycle

2) Role of Aspartate in TCA cycle

Oxaloacetate, the keto acid obtained from Aspartate by transamination is an intermediate of TCA cycle (Figure-2). Oxaloacetate can either be utilized in TCA cycle or be channeled to the pathway of gluconeogenesis.

Hence aspartate is a common intermediate of TCA cycle (through Oxaloacetate) and Urea cycle (directly).

AST

Figure-2- The transamination reaction is catalyzed by Aspartate amino transferase that requires B6-P as a coenzyme.

As regards other options-

Tyrosine upon metabolism forms fumarate and acetoacetate. Fumarate can be utilized in TCA cycle directly but unlike aspartate it can not be incorporated directly in Urea cycle.

Lysine and Leucine are ketogenic amino acids; they produce acetyl coA upon metabolism that has no role in urea formation . Acetyl coA although is a substrate of TCA cycle, but it does not share any relation with urea cycle.

Tryptophan is both glucogenic as well as ketogenic amino acid, it produces pyruvate as well as acetoacetate; both of these products have no connection with urea cycle.

Thus Aspartate is the most suited option.

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