• 한국식품영양과학회:학술대회논문집
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• 한국식품영양과학회 2001년도 International Symposium on Food,Nutrition and Health for 21st Century
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• pp.22-37
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• 2001

Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. Serotonin N-acetyltransferase (AA-NAT) which is found to be expressed in pineal gland, retina, and various tissues, catalyses the conversion of serotonin to N-acetylserotonin and is known as the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AA-NAT can be used to treat serotonin-and melatonin-related diseases such as insomnia, depression and seasonal affective disorders (SAD). Several assay methods have been developed by which to measure AA-NAT activity. We have also developed a simple, rapid and sensitive AA-NAT assay method that takes advantage of differences in the organic solubilities between acetyl CoA and N-acetyltryptamine. We screened modulators of AA-NAT activity from the water extracts of the medicinal plants. We found MNP1005 which strongly inhibited the activity of AA-NAT ($IC_{50}$=2.2$\mu$M). Enzyme inhibitory kinetic studies revealed that MNP1005 exhibited a noncompetitive inhibition toward tryptamine. The antidepressant effect of MNP1005 was investigated on behavioral despair test so called forced swimming test (FST). MNP1005 significantly increased swimming behavior by reducing immobility with treatment of 10 mg/kg when compared to the vehicle-treated control group (P < 0.05). This suggests that MNP1005 possesses antidepressant activity. The influence of chronic MNP1005 treatment on the expression of brain-derived neurotrophic factor (BDNF) was examined by in situ hybridization and Northern blot. Chronic treatment of MNP1005 blocked the downregulation of BDNF mRNA in the frontal cortex and other cortex regions in response to restraint stress.

• Environmental Analysis Health and Toxicology
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• 제17권1호
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• pp.73-80
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• 2002

Pyruvate dehydrogenase phosphatase (PDP)와 kinase는 당대사시 해당과정에서의 대사 산물인 pyruvate를 acetyl CoA로 만들어 구연산 회로로 진입시켜 주는 효소인 pyruvate dehydrogenase complex (PDC)의 활성을 조절하는 중요한 효소이다. PDP의 catalytic subunit는 PDC의 dihydrolipoamide acetyltransferase (E2), PDP regulatory subunit (PDPr), 그리고 칼슘 결합 도메인 등으로 구성되어 있는 것으로 추측되어지고 있다. 본 연구에서는 그 구조와 기능과의 상관관계를 알아보기 위해 PDPc를 E. coli JM101에서 발현시켜 순수 정제 후 단백분해 효소를 이용한 제한적 가수분해 방법을 이용해 그 구조와 기능과의 상관관계에 대해 연구하고자 하였다 정제된 PDPc는 trypsin, chymotrypsin, Arg-C 그리고 elastase를 이용하여 3$0^{\circ}C$ 그리고 pH 7.0에서 제한적으로 분해시켰으며 각 분해산물의 아미노 말단의 아미노산 배열을 분석하였다. 그 결과 PDPc는 trypsin, chymotrypsin, elastase에 의해 N-terminal의 50 kD과 C-terminal의 10 kD의 두개의 분해산물을 만들었으며, Arg-C에 의해 50kD의 분해산물은 약 35kD와 15kD으로 더 가수분해가 되었다. 이러한 결과로 볼 때 PDPc는 앞에서 추측한데로 세개의 주요한 기능적 도메인으로 이루어져 있음을 알 수 있었다 또한 C-terminal의 10kD은 PDPc의 활성에는 영향을 주지 않는 것으로 밝혀졌으나 다른 도메인의 기능은 더 연구가 되어져야 할 것으로 생각된다.

• 미생물학회지
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• 제40권1호
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• pp.60-64
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• 2004

Gentamicin에 저항성을 나타내는 세균을 병원 하수로부터 분리하여 aminoglycoside-(3)- N-acetyltransferase를 암호화하는 유전자인 aac(3)II의 존재여부를 dot-blot hybridization으로 조사하였다. aac(3)II유전자의 일부를 탐침으로 사용한 결과 gentamicin저항성 세균의 41% (39/95)가 이 유전자를 가지고 있었다. aac(3)II와 Tn3에서 각각 설계된 primer를 사용한 PCR 결과 aac(3)II를 가지고 있는 39개 균주 중 13개 균주가 TnS-aac(3)II구조를 가지고 있음을 알 수 있었다. aac(3)II의 상류에 Tn3를 가지고 있는 13개 균주의 gentamicin에 대한 최소억제농도는 가지고 있지 않은 균주에 비해 상대적으로 높았다. 13개 균주를 동정한 결과 5개는 Eschelichia coli, 3개는 Acinetobacter johnsonii, Enterobacter agglomerans와 Micrococcus luteus가 각각 2개, 그리고 1개의 Pseudomonas facilis로 동정되었다. 이러한 결과들은 Tn3-aac(3)II구조가 gentamicin 저항성 세균들에서 널리 분포하고 있음을 말해준다.

• Molecules and Cells
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• 제20권1호
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• pp.90-96
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• 2005

A cluster of genes for ribostamycin (Rbm) biosynthesis was isolated from Streptomyces ribosidificus ATCC 21294. Sequencing of 31.892 kb of the genomic DNA of S. ribosidificus revealed 26 open reading frames (ORFs) encoding putative Rbm biosynthetic genes as well as resistance and other genes. One of ten putative Rbm biosynthetic genes, rbmA, was expressed in S. lividans TK24, and shown to encode 2-deoxy-scyllo-inosose (DOI) synthase. Acetylation of various aminoglycoside-aminocyclitol (AmAcs) by RbmI confirmed it to be an aminoglycoside 3-N-acetyltransferase. Comparison of the genetic control of ribostamycin and butirosin biosynthesis pointed to a common biosynthetic route for these compounds, despite the considerable differences between them in genetic organization.

• Journal of Microbiology and Biotechnology
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• 제7권5호
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• pp.329-332
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• 1997

Cell-free extracts of Streptomyces neyagawaensis SL-387 grown on a chemically defined medium supplemented with DL-3-amino-3-phenylpropionic acid (APP) produced N-acetyl-APP (Ac-APP) in the presence of APP and acetyl coenzyme A. The APP obtained by acid hydrolysis of the Ac-APP was D-configuration: $[\alpha]_D+6.5^{\circ}(H_2O)\;at\;20^{\circ}C$, optical purity 92% enantiomeric excesses (ee). These results suggest that an N-acetyltransferase exists in the cell-free extract as a novel enzyme with specificity for D-APP.

• Tuberculosis and Respiratory Diseases
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• 제47권4호
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• pp.471-477
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• 1999

연구배경 : 발암물질의 체내 대사효소계인 GSTM1, T1과 NAT1의 유전적다형성의 발현 양상이 폐암발생과 연관성이 있는가를 밝히기 위해 환자-대조군 연구를 수행하였다. 방 법 : 서울대병원에서 병리화적 폐암환자군으로, 비암성요료계질환으로 입원한 환자를 대조군으로 설정하여, 각 환자에 대한 성, 연령, 흡연력 등을 병력조사나 병록지검토로 얻었으며, 말초혈액을 채취하여 DNA를 분리한 뒤, 다중중합효소연쇄반응을 이용하여 GSTM1, T1의 유전자형을, nested PCR법을 이용하여 NAT1의 유전자형을 결정하였다. 결 과 : 모집된 환자, 대조군은 각각 118 명, 150명이었고, 환자군에서 흡연력은 통계적으로 의미있게 높았다(p<0.05). GSTM1의 소실형은 비소실형에 비해 편평상피암의 위험을 높였으나(OR=2.25 ; 95% CI=1.12-4.51), GSTT1의 경우는 폐암의 위험인자로 작용하지 않았다. NAT1의 fast acetylator형은 폐암환자전체를 분석했을 때 통계적으로 의미있는 위험도 상승을 보였다(OR=2.13; 95% CI=1.04-4.40). 결 론 : GSTM1의 소실형과 NAT1의 fast형은 폐암발생과 관련성이 있다.

• Toxicological Research
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• 제23권3호
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• pp.189-196
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• 2007

Cytochrome P450 (P450) enzymes are the major catalysts involved in the biotransformation of various drugs, pollutants, carcinogens, and many endogenous compounds. Most of chemical carcinogens are not active by themselves but they require metabolic activation. P450 isozymes playa pivotal role in the metabolic activation. The activation of arylamines and heterocyclic arylamines (HAAs) involves critical N-hydroxylation, usually by P450. CYP1A2 plays an important role in these reactions. Broad exposure to many of these compounds might cause carcinogenicity in animals and humans. On the other hand, P450s can be also involved in the bioactivation of other chemicals including alcohols, aflatoxin B1, acetaminophen, and trichloroethylene, both in humans and in experimental animals. Understanding the P450 metabolic activation of many chemicals is necessary to develop rational strategies for prevention of their toxicities in human health. An important part is the issues of extrapolation between species in predicting risks and variation of P450 enzyme activities in humans.

• Journal of Preventive Medicine and Public Health
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• 제31권2호
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• pp.275-284
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• 1998

1996년 3월부터 1996년 12월까지 충북대학교병원 비뇨기과에 입원하여 치료를 받은 방광암 환자 67명과 암 아닌 다른 질환을 가진 대조군 67명을 대상으로 흡연, 음주, 직업력 등을 포함한 생활 습관과 NAT2와 GSTM1, 그리고 GSTT1 유전자 다형성 양상을 조사하여 다음과 같은 결론을 얻었다. 1. NAT2 다형성 분포는, 환자군이 slow, intermediate, rapid acetylator가 각각 3.0%, 38.8%, 58.2%, 그리고 대조군이 7.6%, 40.9%, 51.5%였으며, NAT2의 활성과 방광암 위험도 사이의 관련성은 유의하지 않았다($\chi^2_{trend}=1.18$, P-value>0.05). 2. GSTM1 결손은 환자군의 68.7%, 대조군의 49.3%에서 확인되었으며, OR(95% 신뢰구간)이 2.23(1.12-4.56)으로, 방광암 발생의 위험인자로 나타났다. 3. GSTT1은 환자군의 26.9%,그리고 대조군의 43.3%에서 결손이 있는 것으로 나타나서, GSTT1 결손은 방광암에 대하여 보호효과가 있는 것으로 관찰되었다(OR: 0.48, 95% 신뢰구간: 0.23-0.99). 4. 흡연 여부는 방광암의 발생에 유의한 영향을 미치지 않는 것으로 나타났는데(OR=1.85, 95% CI: 0.85-4.03), 이는 환자군과 대조군의 흡연률이 모두 높기 때문으로 판단된다. 5. 그 외, 음주력, 직업력, 수혈 여부, 그리고 피임시술의 과거력 등의 요인들은 방광암 발생과 유의한 관련성이 없는 것으로 나타났다.

• 한국발생생물학회지:발생과생식
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• 제23권2호
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• pp.149-160
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• 2019

This study examined the effects of different photoperiod conditions on olive flounder (Paralichthys olivaceus), a commercially important species in Korea. Daily variations in the expression of mRNA for the growth-related genes arylalkylamine N-acetyltransferase2 (AANAT2), preprosomatostatin1 (PSS1), and growth hormone (GH) were examined under a 12 h light:12 h dark photoperiod. All the genes were expressed at higher level during the dark period. Melatonin injections increased the expression of GH, but did not significantly affect the expression of PSS. Under short-day conditions (10 h:14 h), the fish gained more weight than under long-day conditions (14 h:10 h). A long nighttime induced melatonin secretion and increased the expression of GH mRNA, promoting weight gain in this species. Therefore, we thought that the long day condition in raising olive flounder may be effective in inducing body growth.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제22권4호
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• pp.373-382
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• 2000

Individual genetic susceptibilities to cancers may result from several factors including differences in xenobiotics metabolism to chemical carcinogens, DNA repair, altered oncogenes and suppressor genes, and environmental carcinogen exposures. Among them, genetic polymorphisms of metabolizing enzymes to chemical carcinogens have been recognized as a major important host factors in human cancers. They have two main types of enzymes: the phase I cytochrome P-450 mediating enzymes (CYPs) and phase II conjugating enzymes. The purpose of this study is to determine the frequencies of genotypes of phase I (CYP1A1 and CYP2E1) and phase II (NAT2) metabolizing enzymes in healthy control and head and neck cancer patients of Korean and to identify the relative high risk genotypes of these metabolizing enzymes to head and neck cancer in Korean. The author has analyzed 132 head and neck cancer patients and 113 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results were as following; 1. The frequencies of genotypes of CYP1A1, CYP2E1 and NAT2 in healthy control were as following; CYP1A1 exon 7 polymorphism; Ile/Ile: Ile/Val: Val/Val = 59.3%: 36.3%: 4.4% CYP2E1 Pst I polymorphism, C1/C1: C1/C2: C2/C2 = 61.1%: 32.1%: 6.2% NAT2 polymorphism; F/F: F/S: S/S = 43.4%: 48.7%: 8.0% 2. In analysis of phase I enzyme, Val/Val genotype in CYP1A1 exon 7 polymorphism and C2/C2 genotype in CYP2E1 Pst I polymorphism were associated with relative high risks to head and neck cancers (Odds' ratio: 2.09 and 1.37, respectively). 3. Among the genotypes of NAT2 enzyme polymorphism, S/S genotype of NAT2 enzyme had 1.03 times of relative risk to head and neck cancers. 4. In combined genotyping of CYP1A1, CYP2E1, and NAT2 enzymes polymorphisms, the patients with Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator had higher relative risks than the patients with each baseline of combined genotypes (Odds' ratio: 2.82, 1.98 and 2.1, respectively). These results suggest the combined genotypes of Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator were more susceptible to head and neck cancers in Korean. And genotyping of metabolizing enzymes could be useful for predicting individual susceptibility to head and neck cancer.