Question

A patient has a genetic mutation in the gene for glutaminase that significantly reduces the efficiency of this enzyme, leading to a decrease in glutamatergic signaling. Which of the following could potentially compensate for this?

	a.	A downregulation of aspartate aminotransferase
	b.	A downregulation of VGLUT
	c.	An upregulation of neuronal glutamate transporters
	d.	An upregulation of VIAAT

Answer 1

Ans.) Option C : An upregulation of neuronal glutamate transporters

Explanation: Glutaminase is an important enzyme which is often expressed in post synaptic neurons where it converts glutamine into glutamate. Glutamate is most common neurotransmitter. Due to declined glutaminase , the level of glutamate gets declined in neurons and hence glutamatergic signaliing are affected.

Hnece best method to conpensate compromised glutaminase function is to upregulate glutamate transporter so that glutamate are directly transported inside the cells.

Aspartate aminotransaminase is enzyme which is responsible for reversible transfer of amino group between aspartate and glutamate. So , downregulation of this enzyme will play no role in compensation declined glutamate level. However, it will further decline glutamate level.

VGLUT (vesicular glutamate transporter) are expressed in different body regions and are responsible for uptake of glutamate. Downregulation of VGLUT is also not good solution for declined glutamate level in neurons.

VIAAT (vesicular inhibitory amino acid transporter) responsible for transport of GABA and glycine. Upregulation of this transporter has no role in compensating declined glutamate level.