Dimetilarjinin dimetilaminohidrolaz (DDAH) enzim aktivitesi ölçüm yöntemi ve klinik uygulamaları
Method of DDAH(dimethylarginine dimethylaminohydrolase) enzyme activity measurement and clinical applications
Yazar: YASEMİN GÜLCAN KURT
Danışman: PROF.DR. M. KEMAL ERBİL
GATA / Tıp Fakültesi / Biyokimya ve Klinik Biyokimya Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2007
Konu: Biyokimya = Biochemistry ; Kardiyoloji = Cardiology

Özet:
Experimental data indicate that nitric oxide (NO) may play a role in thepathophysiology of epilepsy. It is also possible that NO-mediated events are involvedin the expression of the anticonvulsant action of some antiepileptics. ADMA is anendogenous NO synthase inhibitor. Homocysteine is an established atheroscleroticrisk factor. Vitamin B-12 and folate play important roles in homocysteinemetabolism.The aims of this study are defined as, to manifest the functionalinteraction between epilepsy and NO by comparing serum ADMA, homocysteine,folate and vitamin B-12 levels before and after carbamazepine and valproic acidtreatment; to investigate the role of NO in the action of mechanism of AEDs and toevaluate the atherosclerotic risk and metabolic changes in patients who are on longterm AED therapy. 35 patients were included in the study. Patients formed in twogroups as VPA (n=17) and CBZ (n=18) treatment. Blood samples were obtainedbefore AED therapy and at the 3rd. month of therapy. At the 3rd. month, patients hadsignificantly higher ADMA levels (VPA: p=0,002, KBZ: p=0,024) in both groups. InVPA group, pHcy (p=0,005) and VitB-12 (p=0,001) levels were significantly higher. InCBZ group folate levels were significantly lower (p=0,006). Our data suggest thatthese two AEDs exhibit their antiepileptic effects by lowering the NO levels in CNSand increased ADMA and pHcy levels indicate high atherosclerotic risk. Decreasedfolate levels in CBZ group, may cause malfunction in metabolic processes that folateis used as a cofactor.Key Words: Epilepsy, Nitric Oxide, ADMA, Homocysteine pathway, AntiepilepticDrug

Abstract:
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) enzyme. Elevations in plasma ADMA (pADMA) contribute to vascular pathophysiology observed in atherosclerosis. So it is important to keep pADMA levels under control. Generation of free ADMA by sequence of complex events reveals DDAH enzyme, which selectively degrades ADMA, as a target for controlling ADMA levels. In this study developing the method of DDAH enzyme activity (DDAHea) measurement, measuring serum/erythrocyte DDAHea and researching if it is a risk factor for CAD has been aimed. Firstly HPLC method of ADMA measurement was developed then DDAHea was determined by a decrease in the level of ADMA during incubation. This decrease was seen after incubation in erythrocyte samples but similar change wasn?t seen in serum samples and absence of DDAHea in serum was concluded. Then erythrocyte DDAHea (eDDAHea), erythrocyte ADMA (eADMA), pADMA and plasma total homocysteine (ptH) levels were measured in CAD patients (n=40) and 40 patients with normal coronary angiography. According to eDDAHea there weren?t significant difference between groups but pADMA and ptH levels were significantly high in CAD patients. No correlation between eDDAHa and pADMA levels was seen. But a significant negative correlation between eDDAHea and eADMA levels was determined. Our study is the first showing that there is no DDAHea in serum and measuring eDDAHa in a disease group. According to our results eDDAHea is influential on eADMA levels but it hasn?t got any place in regulating pADMA levels and it can not be evaluated as a risk factor for CAD. In addition to this the existence of significant difference in pADMA and ptH levels between two groups, which are likely about total cholesterol, age, gender and smoking status, supported both ADMA and homocysteine as independent CAD risk factors.Keywords : Erythrocyte DDAH enzyme activity, ADMA