Assignment

Q1. Brain cells take up tryptophan, which is then converted to 5-hydroxytryptophan by tryptophan hydroxylase. Aromatic amino acid decarboxylase then catalyzes the formation of the potent neurotransmitter 5-hydroxytryptamine, also called serotonin. In the blood, tryptophan is freely diffusible. The rate of tryptophan concentration is normally well below that of the Km for tryptophan hydroxylase. Aspirin and other drugs displace tryptophan from albumin, thereby increasing the concentration of free tryptophan.

a. What cofactor is required for the activity of tryptophan hydroxylase?

Ans:

Reduced pteridine cofactor. Tetrahydrobiopterin (BH4 or THB).

b. Dietary deficiencies in pyridoxine and related metabolites can induce a number of symptoms, including those that appear to be related to derangements in serotonin metabolism. What enzyme could be affected by a deficiency of vitamin B6?

Ans:

5-hydroxy tryptophan decarboxylase can be affected, so that serotonin is not formed.
Also, vitamin B6 is required for more than 100 enzymes in cellular metabolism. It is used for the amino acid transporter. It is also used for the Glutamate decarboxylase for the conversion of glutamate to GABA. VitB6 is also required for DOPA decarboxylase and the enzyme that converts homocysteine to methionine. Vitamin B6 is also required for all Aminotransferases that catalyze the “transamination” reaction.

c. What effect does aspirin have on tryptophan metabolism in brain cells?

Ans:

Logically tryptophan concentration should be increased due to aspirin and thus more tryptophan should be available in the brain cells to be converted to serotonin. However, the excretion of tryptophan from the blood is increased due to its displacement from albumin resulting in the reduced concentration of Tryptophan in blood. That ultimately causes a reduction in the availability of tryptophan for brain cells and thus the reduction of serotonin production. Hence, in short term, the aspirin may enhance serotonin production and cause a stress suppressive effect, but in long term, it may be useless in the prevention of stress.

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