• Biomedical Science Letters
• /
• v.11 no.4
• /
• pp.473-479
• /
• 2005

Possible mechanism of decreased catechol-O-methyltransferase (COMT) activity in cholestatic rat liver was studied. Hepatic and serum COMT activities were determined from the experimental rats with common bile duct ligation (CBDL). The Michaelis-Menten constants in this hepatic enzyme were also measured. The activities of cytosolic, mitochondrial and mircosomal COMT as well as their Vmax values were found to be decreased significantly in CBDL plus taurocholic acid (TCA) injected group than in the control group, such as CBDL alone groups. However, their Km values in the experimental groups did not vary. Serum COMT activity increased slightly in the CBDL plus TCA injected group than in the control group. The above results suggest that TCA represses biosynthesis of the COMT in the liver. The elevated activity of the serum COMT is believed to be caused by the increment of membrane permeability of hepatocytes upon TCA mediated liver cell necrosis.

• Biomedical Science Letters
• /
• v.11 no.1
• /
• pp.45-49
• /
• 2005

The change of catechol-O-methyltransferase (COMT) activity during regeneration of rat liver was studied. Cytosolic, mitochondrial and microsomal COMTs activities were estimated in regenerating rat livers over a period of ten days after $70\%$ (median and left lateral lobes) partial hepatectomy. The values of Km and Vmax in the hepatic enzymes were also measured. The activities of cytosolic and microsomal COMTs in regenerating rat liver after partial hepatectomy were found to be significantly increased between the second and the third day. Whereas the mitochondrial COMT activity did not change. The Vmax values of the cytosolic and microsomal COMTs in the regenerating rat liver were significantly increased at the second day after partial hepatectomy, however, the Km values of the above hepatic enzymes did not vary in all the experimental groups. Therefore, the results suggest that the biosynthesis of COMT was increased during the regeneration of rat liver.

• BMB Reports
• /
• v.29 no.2
• /
• pp.142-145
• /
• 1996

To investigate the cause of increased plasma catecholamine levels in liver disease, catechol-O-methyltransferase (COMT), which provides a major route of catabolism for circulating catecholamines, was studied under the cholestasis induced by mechanical biliary obstruction in rats. Monoamine oxidase (MAO) activity and the $K_m$ and $V_{max}$ values for both enzymes were also measured. Cytosolic, microsomal, and mitochondrial COMT activities in the cholestatic liver were significantly decreased throughout the experiment. Microsomal, and mitochondrial MAO activity in the cholestatic liver were also significantly decreased. Vmax values of COMT and MAO were lower. Serum COMT and MAO activities were detected after CBD ligation. These results indicate that plasma catecholamine levels are increased in liver disease due to decreased hepatic degradation of catecholamines by decreased activities of COMT and MAO. The decreased activity of these enzymes is caused by decreased biosynthesis and by flowage into the blood from the damaged hepatocyte.

• Bulletin of the Korean Chemical Society
• /
• v.26 no.11
• /
• pp.1695-1700
• /
• 2005

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is an S-adenosylmethionine (SAM, AdoMet) dependent methyltransferase, and is related to the functions of the neurotransmitters in various mental processes, such as Parkinson’s disease. COMT inhibitors represent a new class of antiparkinson drugs, when they are coadministered with levodopa. Based on x-ray structure of rat COMT (rCOMT), the three dimensional structure of human COMT (hCOMT) was constructed by comparative homology modeling using MODELLER. The catalytic site of these two proteins showed subtle differences, but these differences are important to determine the characterization of COMT inhibitor. Ligand docking study is carried out for complex of hCOMT and COMT inhibitors using AutoDock. Among fifteen inhibitors chosen from world patent, nine models were energetically favorable. The average value of heavy atomic RMSD was 1.5 $\AA$. Analysis of ligand-protein binding model implies that Arg201 on hCOMT plays important roles in the interactions with COMT inhibitors. This study may give insight to develop new ways of antiparkinson drug.

• Biomedical Science Letters
• /
• v.13 no.2
• /
• pp.135-140
• /
• 2007

The possible mechanism of decreased catechol-O-methyltransferase (COMT) activity in cholestatic rat liver was studied. Hepatic and serum COMT activities were determined from the experimental rats with choledocho-caval shunt (CCS). The Michaelis-Menten constants in this hepatic enzyme was also measured. The activities of cytosolic, mitochondrial and mircosomal COMT as well as their $V_{max}$ values were found to be decreased significantly in CCS plus taurocholic acid (TCA) injected group than in the control group, such as CCS alone groups. However, their $K_m$ values in the experimental groups did not vary. Seru4m COMT activity increased slightly in the CCS plus TCA injerted group than in the control group. The above results suggest that TCA represses biosynthesis of the COMT in the liver, The elevated activity of the serum COMT is believed to be caused by the increment of membrane permeability of hepatocytes upon TCA mediated liver cell necrosis.

• Korean Journal of Biological Psychiatry
• /
• v.8 no.1
• /
• pp.111-115
• /
• 2001

An association study with Korean alcoholic patients(n=50) and normal controls(n=53) was performed to find the relationship between catechol-O-methyltransferase(COMT) gene polymorphism and alcoholism using polymerase chain reaction-restriction fragment length polymorphism. When we compared the allele and genotype frequencies of Nla III COMT gene polymorphism in alcoholism and normal controls, there was no significant difference between two groups. Our results do not support an association between the Nla III polymorphism of COMT gene and alcoholism.

• 한국생물공학회:학술대회논문집
• /
• 2005.10a
• /
• pp.1006-1006
• /
• 2005

• Clinical and Experimental Reproductive Medicine
• /
• v.41 no.2
• /
• pp.62-67
• /
• 2014

Objective: The objective of this study was to investigate whether there was a correlation between catechol-o-methyltransferase (COMT) gene polymorphism, which is believed to play a role in the etiology of psychotic disorders, and premenstrual syndrome (PMS). Methods: Fifty-three women with regular menstrual cycles, aged between 18 and 46 years and diagnosed with PMS according to the American Congress of Obstetrics and Gynecology criteria were included in this study as the study group, and 53 healthy women having no health problems were selected as the controls. Venous blood was collected from all patients included in the study and kept at $-18^{\circ}C$ prior to analysis. Results: There was no significant difference between the groups in terms of demographic features such as age, body mass index, number of pregnancies, parity, and number of children. No statistically significant difference was observed in terms of COMT gene polymorphism (p=0.61) between women in the PMS and the control groups. However, a significant difference was found between arthralgia, which is an indicator of PMS, and low-enzyme activity COMT gene (Met/Met) polymorphism (p=0.04). Conclusion: These results suggested that there was no significant relationship between PMS and COMT gene polymorphism. Since we could not find a direct correlation between the COMT gene polymorphism and PMS, further studies including alternative neurotransmitter pathways are needed to find an effective treatment for this disease.

• Food Science of Animal Resources
• /
• v.31 no.4
• /
• pp.506-512
• /
• 2011

This study was conducted to validate the theoretical feasibility of a technique to identify biomarkers in Korean native black pig (KNP) and a commercial Landrace breed. Using two-dimensional electrophoresis, we found six proteins (NADH dehydrogenase Fe-S protein 1, an unnamed protein product, similar to T-complex protein 1, annexin V = CaBP33 isoform, fatty acid-binding protein, and catechol O-methyltransferase), which appeared in KNP alone. We raised polyclonal antibodies (used as the primary antibody) for Western blotting to confirm the characteristics of the six KNP proteins. As a result, catechol O-methyltransferase, annexin V = CaBP33 isoform, and the unnamed protein product presented thicker bands in KNP than those in Landrace. Moreover, catechol O-methyltransferase was shown to be more feasible as a biomarker for KNP. However, cross-reactivity was observed with the polyclonal antibodies for KNP and the other three proteins (NADH dehydrogenase, a protein similar to T-complex protein 1, and fatty acid-binding protein). This study only showed limited results from a limited number of animals; however, our research suggests possibilities for future studies.

• Genomics & Informatics
• /
• v.19 no.1
• /
• pp.7.1-7.13
• /
• 2021

Levodopa (L-DOPA) therapy is normally practised to treat motor pattern associated with Parkinson disease (PD). Additionally, several inhibitory drugs such as Entacapone and Opicapone are also cosupplemented to protect peripheral inactivation of exogenous L-DOPA (~80%) that occurs due to metabolic activity of the enzyme catechol-O-methyltransferase (COMT). Although, both Entacapone and Opicapone have U.S. Food and Drug Administration approval but regular use of these drugs is associated with high risk of side effects. Thus, authors have focused on in silico discovery of phytochemicals and evaluation of their effectiveness against human soluble COMT using virtual screening, molecular docking, drug-like property prediction, generation of pharmacophoric property, and molecular dynamics simulation. Overall, study proposed, nine phytochemicals (withaphysalin D, withaphysalin N, withaferin A, withacnistin, withaphysalin C, withaphysalin O, withanolide B, withasomnine, and withaphysalin F) of plant Withania somnifera have strong binding efficiency against human COMT in comparison to both of the drugs i.e., Opicapone and Entacapone, thus may be used as putative bioenhancer in L-DOPA therapy. The present study needs further experimental validation to be used as an adjuvant in PD treatment.