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Tyrosine Kinase And The Importance In Biological System

1477 words - 6 pages

Tyrosine is a nonessential amino acid, which is synthesized by hydroxylation of an essential amino acid phenylalanine. Protein Kinases are group of enzymes that play an important role in the complexity of the several biological systems present in the human body. The genetic information of humans is known to consist of about 500 protein kinases, which are structurally identified by having a 3-dimensional structure.1
Tyrosine kinases are enzymes that catalyze the transfer of phosphate groups to residues of tyrosine by the use phosphate obtained from Adenosine Triphosphate (ATP). Protein phosphorylation is the process of introducing a phosphate group to a protein, which causes a change in ...view middle of the document...

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Figure 3: Cartoon Rendering of Tyrosine kinase


Figure 4: Surface rendering tyrosine kinaase showing the binding site of the cofactor and the width of the binding channel.
Role and Benefit of Tyrosine Kinase
Tyrosine kinases are located on the cell surface, in the cytoplasm and they are usually involved in the development, and spread of different cancer types, which makes tyrosine kinase important for cancer therapy. Tyrosine kinase inhibitors have been discovered to have effects against different types of cancer.
Cancer chemotherapy is one of the major medical problems in the recent years because the drugs used for the therapy are sometimes ineffective and even when they are effective, it is usually only for a short period of time. Tyrosine kinase inhibitors have been discovered to have effective antitumor activities because they can compete with the ATP binding site of several oncogenes.
The use of chemotherapy is usually ineffective because it usually does not distinguish between normal cells and tumor cells, since they both undergo division. This is why the used of tyrosine kinase inhibitors for cancer therapy is important, since it can be used in targeting only the tumor cells. Tyrosine kinase plays an important role in cancer therapy since it is necessary in the growth factor signaling. The activation of tyrosine kinase can lead to an increase in the growth of tumor cells. In table 1 the tyrosine kinase inhibitors associated with specific mutations are listed.5

Table 1: Tyrosine kinase inhibitors and their mutations.5
Chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) are caused by abnormalities of the t translocation or Philadelphia chromosome which results in the production of BCR-ABL oncogenes by the binding together of the BCR gene onto chromosome 22 and the ABL gene onto chromosome 9. This causes the p210 and p190 to be expressed. The expression of these two forms of protein causes further irregular signaling, resistance of cell death to the cells that are supposed to be differentiating into specific cell types and then causes an increase in the amount of myeloid cells present. These abnormalities lead to the making of the tyrosine inihibitor, imatinib. The BCR-ABL is ideal for targeting imatinib because the mutation of BCR-ABL is found in all patients with chronic myeloid leukemia. In a study carried out in 1997 by Drunker et al., it was discovered that imatinib was not only able to specifically get rid of rapidly multiplying myeloid cells containing BCR-ABL without any negative or toxic effects to normal cells, but it also reduced the amount of BCR-ABL cells formed by about 95%. Imatinib is usually used in the treatment of newly diagnosed patients or patients who did not respond well to interferon-α therapy.5Even though there has been successful use of imatinib, it is till limited, but hopefully the present knowledge of its effects will help in creating more developed drugs that can target...

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