Uracil Compounds As Inhibitors For Glutamate Oxaloactate Tansaminase (GOT) In Serum Of Some Leukemia Patients

Effect of Uracil’s derivatives on enzyme glutamate oxaloacetate transaminase (GOT) for sample of normal human and some types of leukemia patients, acute lymphatic(ALL) (11 cases), acute mylosyticl (AML) (4 cases), acute mylomonocyticl (AMOL) (2cases), acute promylocyticl (APL) (3 cases), chronic mylobid (CM) (4 cases) and chronic lymphatic (CLL) (4 cases) is investigated. The ages of patients are between (10-69 years). Some synthesized derivatives of uracil were used as an inhibitors and a comparison between the activity of (GOT) in the presence and absence of inhibitors for two-types of serums under the same conditions is studied. The percentage of inhibition and type of inhibition is also included in this study, which was showed degree of inhibitions in normal individuals between (31% 73%) and degree of inhibitions in patient’s individuals between (25% 80%) which showed that inhibition was significantly higher in the sera of patient with leukemia. The activity was determined colorimetrically by Retiman and Frankel method. Keyword: GOT, uracil, leukemia, pyrimidine Kirkuk University Journal /Scientific Studies (KUJSS) Volume 10, Issue 3, September 2015 , p.p(320-331) ISSN 1992 – 0849 Web Site: www.kujss.com Email: kirkukjoursci@yahoo.com, kirkukjoursci@gmail.com 023 ( ييهلاا ةعووجول لقاٌلا نيزًلاا ىلع تاطبثوك ليسارويلا تابكره GOT ) مذلا ىاطرس عاوًا ضعبب ييباصولا ىضرولا لوصول جاح رداق ةيداً ءايويكلا نسق / مولعلا ةيلك / كوكرك ةعهاج hajnadia@yahoo.co.uk :ثحبلا ملاتسا خيرات 22 / 6 / 2333 :ثحبلا لوبق خيرات 22 / 32 / 2330 صخلولا ةسا رد ثحبلا نمضت ريثأت نيملاا ةعومجمل لقانلا ميزنا ىمع ةرضحملا ليسا رويلا تاقتشم ضعب glutamate oxaloacetate transaminase ( GOT نيباصملا مد لصم نم جذامنو يعيبطلا يرشبلا مدلا لصم نم جذامنل ) )ةداحلاو نمزملا( مدلا ناطرسب 82 نيب نيباصملا رامعا حاورت ثيح ءاحصلاا صاخشلاا لوصم عم ةنراقم ةلاح 01 96 دوجوب ميزنلاا ةيلاعف سايق مت ةسا ردلا هذه يف . اماع نم نيعونلا لاكل اهدوجو مدعبو تاطبثمك ليسا رويلا تاقتشم عون ةفرعم كلذكو طيبثت ةبسن ىمعا اهل تاطبثملا نم يا ةفرعمو طيبثتلا بسن باسحو فورظلا سفن تحت لوصملا نيب حوا رتت ءاحصلاا صاخشلاا لوصم يف طيبثت ةبسن اهل تابكرملا هذه ناب ةسا ردلا ترهظا ثيح . طيبثتلا (31% 73%) ( نيب حوا رتت نيباصملا صاخشلاا لوصم يف يف امنيب 82 % 21 نامترل يرتمرمكلاا ةقيرط تمدختسا دقو. )% ( ميزنلاا ةيلاعفل طبثمك ريبك ريثات ليسا رويلا تابكرمل نا ثحبلا رهظا دقو. ميزنلاا ةيلاعف باسح يف لكنا رفو GOT يف ) .)ةداحلاو نمزملا( مدلا ناطرسب نيباصملا مد لصم ممكلا :ةلادلا تا نيدميربلا ؛مدلا ناطرس ؛ليسا رويلا ؛نيملاا ةعومجمل لقانلا ميزنا .

normal, but may rise to twice the upper reference limit", Skeletal muscle diseases, after trauma or surgery and severe hemolytic anemia [2] Miekl concluded that there is an increase in GOT enzyme in the case of Acute lymphatic and this is because the enzyme is liberated from the carcinogenic cell as result of their destroy [3]. Inhibitor are different in their chemical nature and its biological activity their the response of the enzyme type differ in their activity toward inhibitors, many organic compound were used as inhibitors for GOT enzyme for exampel (Glutaric acid, Maliec acid, Acetate and Benzoate) [4] .An increase in the SGPT, SGOT and SALP activities was recorded in diabetic rats in comparison with non-diabetic rats, indicating an altered liver function in diabetic condition [5]. SGOT is found nearly in every tissue of the body including RBC. It is present in high concentration in muscle, myocardium, and liver. The serum SGOT concentrations increase shortly after the myocardial infraction and hepatic parenchymal injury. The measurement of the serum SGOT is therefore helpful for the diagnosis of myocardial infraction, hepatocellular diseases and skeletal muscles disorders [6].The aim of the present study is to investigate the effect of Uracil's derivatives on GOT enzyme.

2.MATERIALS AND APPARATUS
Aspartic acid, Na 2 HPO 4 , KH 2 PO 4 , NaCl was purchased from, BDH CO., αketoglutrate and 2, 4-dinitrophenyl hydrazine was purchased from Hopkins and Williams CO., All chemicals used were of analytical grad. Uracil's derivatives were prepared according of the literature [7]  Venipuncture and kept to clott for 2 hours at room temperature, and then the serum was separated by centrifugation at 3000 round per minutes for 10-20 min.

3.METHODS
The activity was determined colorimetrically by Retiman and Frankel method [8].The

4.RESULTS AND DISCUSSION
There are many studies on uracil derivatives showed that there are acting an important roles and its active biologically, study on this molecules showed it were importance as anticancer and antiviral agents. [11] Recently a study reported that these compounds should play an important role in biological systems and have considerable attention in pharmacology. [12] In addition anther study illustrated that series of new carbocyclic uracil derivatives evaluated as potential anti tuberculosis agents and its completely inhibited the growth of mycobacterium tuberculosis. [13] In order to study the effect of some uracil derivatives as inhibitor of the activity of GOT in the serum of patients of various kind of Leukemia and according to the method above we found that these synthesized uracil derivatives act as inhibitor as illustrated in the Table (2) which was showed the values of activity of GOT in the serum of patients with Leukemia of various types, values of protein concentration, and specific activity, also we measured the activity of GOT in the normal serum in order to compare with the serum of patients and these was showed that some GOT activity values for normal human are surprisingly higher than that reported [14] and these data was showed in Table ( (1), (2) and (4) were found to have higher inhibition effect on serum GOT in normal than patients.
Compounds (5) and (6) were found to have higher inhibition effect on serum GOT in patients than normal. Compound; (3) showed same inhibition effect on serum GOT in normal and patient. Compounds (6) was found to have higher inhibition effect on serum GOT in patients, while compound (1) was found to have higher inhibition effect on serum GOT in normal .
The k i value of the compounds in this study with (0.1 M) concentration for (Aspartic and αketoglutrate) and the type of inhibition summarized in Table ( 4). Figures (l), (2), (3) and (4) illustrates the types of the inhibitory effect of the compounds (1), (3), (4) and (6) individually.

5.CONCLUSION
In this research it was established that the data on GOT inhibition confirmed that the Uracil's derivatives showed that inhibition was significantly higher in the sera of patient with leukemia.