Professional Documents
Culture Documents
Act 11 Compilation
Act 11 Compilation
LABORATORY ACTIVITY # 11
SUBMITTED BY:
GROUP 3
Gadingan, Christian
Mangaoang, Allen
SUBMITTED TO:
DATE SUBMITTED:
Tryptophan is an amino acid needed for normal growth in infants and for nitrogen balance in
adults. According to Pike and Bethesda (2019), the body uses tryptophan to help make niacin, melatonin,
and serotonin. Looking deeper, serotonin is thought to produce healthy sleep and a stable mood.
Additionally, Serotonin (5-HT) is a monoamine implicated in a variety of physiological processes that
functions either as a neurotransmitter or as a peripheral hormone important for the pathophysiology of
depressive disorders (Mosienko, Bashammakh & Bader, 2010). Furthermore, tryptophan hydroxylase is
an enzyme involved in the synthesis of the neurotransmitter serotonin (Hazegawa, 2010). It has been
already determined that this rate-limiting enzyme Tryptophan hydroxylase (TPH) develops in the cortex
and brainstem (Mosienko et al, 2019)
RESULTS AND FINDINGS
Table 1 shows how the correlation between the activity which is the log of the IC50 and the other
one as the molecular descriptors (Hy) and the charge descriptors (QCmax, QNmin). Following the
pioneering work of the “NCI-60”, a collection of 59 human cancer cell lines developed by the National
Cancer Institute for in vitro drug screening, recent hallmark studies have shown that screening very large
cell line collections can recapitulate known and identify novel molecular genomic determinants of drug
sensitivity. (Menden, et. al., 2013)
The formula that was formulated in the multiple linear regression for the analysis of inhibition activity of
the nucleoside analogues:
% inhibition = + + + + +C
C = Y-intercept
As seen in table 2, it shows the multiple linear regression analysis table between the activity and
the descriptors that were chosen. By using the multiple linear regression, it shows a significant value in
the significance F which is 10.29E < 0.05 or p-value<0.05. In the model, the confidence level that was
used was 95% confidence interval. A significant value in the significance F, means that the model that
was used in the study was valid or accepted.
CONCLUSION
The mechanisms occurring within the body is caused by the collective interactions of chemical
systems within the human body. Tryptophan hydroxylase (TPH) catalyzes the 5-hydroxylation of
tryptophan, which is the first step in the biosynthesis of indoleamines which are serotonin and melatonin.
This essential amino acid is classified as neutral, and nonpolar because of the inert and hydrophobic
nature of the benzyl side chain. Limitations observed in this analysis include the inability of the model to
address non-linear relationships. Also, as all the previous activities have always pointed out, the results
obtained are merely approximations and so the results are not always accurately observed in the natural
biochemical systems within the body
In the study of Zhong et al. (2013), Tryptophan hydroxylase 1 (TPH1) is being used as a way of
producing or synthesizing serotonin. In the study, it shows how inhibitors like naphthalene, will interact
with the TPH1 so that its function will be able to be stopped. In the conclusion, it was verified that the
intermolecular forces that enables inhibitors to do its job is due to the hydrogen bond and Van der Waal
interaction, and that is directed by the hydrophobic interaction between the two substances, such that it
enables the inhibitor substance to target TPH1.
In the case of the study of Waløen et al. (2017), the two Tryptophan hydroxylase are derived from
two different genes in which TPH1 is derived at chromosome 11 while on the other hand, Tryptophan
hydroxylase 2 (TPH2) is located at chromosome 12. This turns to give a 71% similarity between the two
proteins. In the interaction between the TPH2 and phenylalanine derivative, this might not be able to
inhibit the activity of the TPH2 as there might be some molecular interactions that is different from TPH1.
REFERENCES:
Pike, R., & Bethesda. (2019, November 6). Tryptophan: MedlinePlus Medical Encyclopedia. Retrieved
from https://medlineplus.gov/ency/article/002332.htm.
Mosienko, V., Bashammakh, S., Alenina, N., & Bader, M. (2010). Tryptophan Hydroxylase as Novel
Target for the Treatment of Depressive Disorders. Pharmacology, 85(2), 95–109. doi:
10.1159/000279322
Menden MP, Iorio F, Garnett M, McDermott U, Benes CH, Ballester PJ, et al. (2013) Machine Learning
Prediction of Cancer Cell Sensitivity to Drugs Based on Genomic and Chemical Properties. PLoS ONE
8(4): e61318. https://doi.org/10.1371/journal.pone.0061318
Waløen, K., Kleppe, R., Martinez, A., & Haavik, J. (2017). Tyrosine and Tryptophan Hydroxylases as
Therapeutic Targets in Human Disease. Expert Opinion on Therapeutic Targets, 21(2), 168. doi:
10.1080/14728222.2017.1272581
Zhong, H., Huang, W., He, G., Peng, C., Wu, F., & Ouyang, L. (2013). Molecular Dynamics Simulation of
Tryptophan Hydroxylase-1: Binding Modes and Free Energy Analysis to Phenylalanine Derivative
Inhibitors. International Journal Of Molecular Sciences, 14, 9947, 9960. doi:
10.3390/ijms14059947