biochemistry 1. Tryptophan hydroxylase is an enzyme that catalyzes the posttrans
ID: 196008 • Letter: B
Question
biochemistry
1. Tryptophan hydroxylase is an enzyme that catalyzes the posttranslational modification of the amino acid tryptophan (shown below). As the name implies it adds a hydroxyl group to a tryptophan residue on a protein. Based on your knowledge of Biochemistry what new non-covalent interactions form upon the action of the enzyme? (5 points) CH2 HN 2. Suppose there was another enzyme called tryptophan kinase. What new noncovalent interactions would form from its action? (hint: see slide 46 in the ppt for Chapter 3 (5 points)Explanation / Answer
Hypertryptophanemia is a rare inheritedmetabolic disorder probably caused by a blockage in the conversion of tryptophan to kynurenine, resulting in the accumulation of tryptophan and some of its metabolites in plasma and tissues of affected patients. The patients present mild-to-moderate mental retardation with exaggerated affective responses, periodic mood swings, and apparent hypersexual behavior. Creatine kinase plays a key role in energy metabolism of tissues with intermittently high and fluctuating energy requirements, such as nervous tissue. The main objective of the present study was to investigate the effect of acute administration of tryptophan on creatine kinase activity inbrain cortex of Wistar rats. We also studied the in vitro effect of this amino acid on creatine kinase activity in the brain cortex of non-treated rats. The results indicated that tryptophan inhibits creatine kinase in vitro and in vivo. We also observed that the in vitro inhibition was fully prevented but not reversed by pre-incubation with reduced glutathione, suggesting that the inhibitory effect of tryptophan on CKactivity is possibly mediated by oxidation of essential thiol groups of the enzyme and/or long-lasting adduct formation. Considering the importance of creatine kinase for the maintenance of energy homeostasis in the brain, it is conceivable that an inhibition of this enzyme activity in the brain may be one of the mechanisms by which tryptophan might be neurotoxic.
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