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Early nutritional changes modify the kinetics and phosphorylation capacity of tryptophan-5-hydroxylase
G G Manjarrez1, G G Chagoya, J Hernández
1Department of Physiology, Biophysics and Neurosciences, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, México, D.F.
Insights
Developmental malnutrition accelerates brain serotonin production by increasing L-tryptophan (L-Trp) and activating tryptophan-5-hydroxylase (TrpOH). Malnutrition alters TrpOH, enhancing its affinity for L-Trp and response to phosphorylation, suggesting structural enzyme changes.
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- Gestational malnutrition impacts brain development and neurotransmitter pathways.
- Serotonin biosynthesis is crucial for brain development, involving L-tryptophan (L-Trp) and tryptophan-5-hydroxylase (TrpOH).
Purpose of the Study:
- To investigate the mechanism of tryptophan-5-hydroxylase (TrpOH) activation in the developing rat brain under conditions of gestational malnutrition.
- To compare the kinetic properties and response to phosphorylation of TrpOH in malnourished versus normal developing brains.
Main Methods:
- Kinetic experiments were conducted using varying L-tryptophan (L-Trp) concentrations in rat brains at different developmental ages.
- The activity of tryptophan-5-hydroxylase (TrpOH) was assessed under various enzyme phosphorylation conditions in both malnourished and control groups.
Main Results:
- Brains from malnourished rats exhibited lower Km values for TrpOH, indicating increased affinity for L-tryptophan (L-Trp), with no significant change in Vmax compared to controls.
- Tryptophan-5-hydroxylase (TrpOH) demonstrated enhanced activity under tested phosphorylating conditions in the malnourished group.
Conclusions:
- Developmental malnutrition alters brain tryptophan-5-hydroxylase (TrpOH) not only by increasing substrate availability (L-tryptophan) but also by modifying the enzyme's intrinsic properties.
- Malnutrition appears to induce structural changes in the TrpOH molecule, leading to higher affinity for L-tryptophan and increased responsiveness to phosphorylation, thereby accelerating serotonin synthesis.
Abstract:
Gestational malnutrition induces an acceleration of the serotonin biosynthetic pathway in the developing brain with an increase in brain L-tryptophan (L-Trp), tryptophan-5-hydroxylase (TrpOH) activity and serotonin content. In the present work we report results on the possible mechanism of TrpOH activation. Kinetic experiments were done with different L-Trp concentrations in the rat brain at different ages. Also various phosphorylating conditions of the enzyme were tested in order to compare its activation in developmentally malnourished and normal brains. The results showed lower Km values and no changes in the Vmax in the malnourished as compared to controls. Interestingly, in the malnourished group, TrpOH showed an increased activity under the phosphorylating conditions employed. We propose that in the activation of brain TrpOH by developmental malnutrition, not only is an elevation of L-Trp involved, but also a change in the enzyme itself reflected in a higher affinity for L-Trp and in a greater response to phosphorylation. This allows us to propose the possibility that early chronic malnutrition induces structural changes in the enzymatic molecule.